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Mitchel is a reporter for MDedge based in the Philadelphia area. He started with the company in 1992, when it was International Medical News Group (IMNG), and has since covered a range of medical specialties. Mitchel trained as a virologist at Roswell Park Memorial Institute in Buffalo, and then worked briefly as a researcher at Boston Children's Hospital before pivoting to journalism as a AAAS Mass Media Fellow in 1980. His first reporting job was with Science Digest magazine, and from the mid-1980s to early-1990s he was a reporter with Medical World News. @mitchelzoler
Participatory surveillance gains ground in U.S., Brazil
VIENNA – Participatory surveillance has begun to enter mainstream public health.
The Brazilian Ministry of Health arranged for distribution of a participatory surveillance app for monitoring 10 symptoms in people attending or working at 2014 FIFA World Cup events. The smart phone app had 9,434 downloads, 7,155 registered users, and 4,706 active users who sent a message about their symptom status at least three times during the World Cup last June and July in Brazil, Dr. Marlo Libel said at the International Meeting on Emerging Diseases and Surveillance. “Healthy Cup 2014” became the first participatory surveillance tool ever used at a mass gathering event, he said.
“We demonstrated that direct self-reporting during a short period of time could be an excellent tool to complement other surveillance activities,” said Dr. Libel, a medical epidemiology consultant who worked with the Skoll Global Threats Fund on the Brazilian project. Officials at the Brazilian Ministry of Health were so pleased with the program that they are planning with Skoll to release similar apps for Carnival in Feb. 2015 and then for the 2016 Summer Olympics, Dr. Libel said.
Flu Near You shows U.S. growth
Longer-term participatory surveillance of U.S. residents began with the launch of the Flu Near You program in 2012, and by October 2014 it had roughly 100,000 U.S. participants, said John S. Brownstein, Ph.D., an epidemiologist at Harvard Medical School in Boston and cofounder of Flu Near You.
That level is large enough to provide meaningful information, according to Matthew Biggerstaff, an epidemiologist at the Centers for Disease Control and Prevention in Atlanta, as well as other public health officials.
“We’ve been really excited at CDC about Flu Near You because it gives us a view of influenza illness that goes beyond the medically attended cases we base our usual surveillance on,” said Matthew Biggerstaff, an epidemiologist in the CDC’s influenza division. “It adds timeliness because we usually have a 1-week lag” in reporting data from outpatient physician visits and hospitalizations. Flu Near You, which asks participants to report weekly on whether they have any of 10 symptoms gives information that goes beyond the flu-like illness tallied by standard CDC surveillance. “We do not think that it will replace our traditional health care–based surveillance, but it gives us another set of data to look at,” Mr. Biggerstaff said in an interview.
The 10 symptoms that Flu Near You prompts users to report on each week are fever, cough, sore throat, shortness of breath, chills or night sweats, fatigue, nausea and vomiting, diarrhea, body ache, and headache. New participants are also asked whether they received a flu shot during the prior season, Aug. 1-July 31, as well as during the current season since the most recent July 31.
Flu Near You and other participatory surveillance tools also offer epidemiologists a way to track the participating cohort over time. That allows assessment of individual attack rates of influenza-like illness and other syndromes and also vaccine efficacy, Mr. Biggerstaff noted.
“It helps give us a feel for what is happening” with influenza. “We have worked with Flu Near You in the past and we continue to think about ways to work together on digital disease surveillance. We promote it to our state and local colleagues. We think it is a good resource for states to have,” he sad. The CDC’s influenza division is also assessing and using other novel forms of surveillance data, such as influenza and flu mentions on Twitter and searches on Google as well as a statistic Google maintains as Flu Trends.
Participatory surveillance is “very exciting” but is also “new and unproven and remains an experiment,” said Dr. Lawrence C. Madoff, director of the division of epidemiology and immunization at the Massachusetts Department of Public Health in Boston. But while participatory surveillance must still prove its role, U.S. public health officials “increasingly” accept the value of data from tools like Flu Near You, Dr. Madoff said in an interview. He cited the endorsement that participatory surveillance received in recent surveillance and early-detection recommendations from the World Health Organization. The 100,000 participants in Flu Near You give it a “critical mass that will become even more robust as it continues to grow,” Dr. Madoff said.
Further growth is clearly a priority for Flu Near You. “We’re now very excited to promote Flu Near You in a big way to try to get more numbers there and see if we can have a faster system for picking up influenza,” said Dr. Mark S. Smolinski, director of global health at Skoll.
“We are still trying to think through how do we get [Flu Near You] into the general consciousness” of more Americans, said Dr. Brownstein. While participants, not all of whom are active every week, provide enough data to show good correlation with the CDC’s routine surveillance on a national scale, if Flu Near You “had enough numbers we could drill down into subpopulations,” he noted. For now, the volume of participation makes subgroups too scanty in size for meaningful analysis, Dr. Brownstein conceded.
Mass gathering surveillance in Brazil
The Brazilian surveillance program at the World Cup was modeled on Flu Near You, but Dr. Libel, Dr. Smolinski, and their collaborators produced the app in about 8 weeks after receiving very short notice of the Brazilians’ interest. The weekly, symptom surveillance questions posed by the app replicated seven symptoms from Flu Near You – fever, cough, sore throat, shortness of breath, nausea and vomiting, diarrhea, and headache – and added three new symptoms to the survey: joint pain, bleeding, and red spots on body. This allowed the Health Ministry to also monitor for outbreaks of other infections including measles, cholera, dengue, and chikungunya, Dr. Libel said. The Brazilian app also asked participants each week whether they had been in contact with anyone who had any of the 10 listed symptoms, and whether they had looked for health care services. No outbreaks of any type occurred in Brazil during the World Cup, but during the period it was actively used 27% of the frequent respondents reported experiencing at least one symptom.
The first Brazilian effort “was basically a pilot program,” with little advance promotion, Dr. Smolinksi said in an interview. Officials of the Brazilian Ministry of Health were “impressed” with the data collected. They also liked the ability of the system to push out information on health care access to registered users, and the potential the app offered to send out urgent public health messages. “What the Health Ministry loved the most was that if there had been an outbreak they could have immediately reached out to fans,” Dr. Smolinski said.
The Ministry has interest in expanded surveillance and outreach programs for Carnival and the 2016 Summer Olympics, and Dr. Smolinski and his associates are hopeful that the International Olympics Committee will be receptive to the program and aid in its promotion during 2016. They are also planning to expand beyond smart phones and include the capability to interact with users via text and voice messages.
“We hope we will have huge numbers at the Olympics,” to better document the role participatory surveillance can play at mass gatherings, Dr. Smolinski said.
Dr. Libel, Dr. Brownstein, Mr. Biggerstaff, Dr. Smolinski, and Dr. Madoff had no disclosures.
On Twitter @mitchelzoler
VIENNA – Participatory surveillance has begun to enter mainstream public health.
The Brazilian Ministry of Health arranged for distribution of a participatory surveillance app for monitoring 10 symptoms in people attending or working at 2014 FIFA World Cup events. The smart phone app had 9,434 downloads, 7,155 registered users, and 4,706 active users who sent a message about their symptom status at least three times during the World Cup last June and July in Brazil, Dr. Marlo Libel said at the International Meeting on Emerging Diseases and Surveillance. “Healthy Cup 2014” became the first participatory surveillance tool ever used at a mass gathering event, he said.
“We demonstrated that direct self-reporting during a short period of time could be an excellent tool to complement other surveillance activities,” said Dr. Libel, a medical epidemiology consultant who worked with the Skoll Global Threats Fund on the Brazilian project. Officials at the Brazilian Ministry of Health were so pleased with the program that they are planning with Skoll to release similar apps for Carnival in Feb. 2015 and then for the 2016 Summer Olympics, Dr. Libel said.
Flu Near You shows U.S. growth
Longer-term participatory surveillance of U.S. residents began with the launch of the Flu Near You program in 2012, and by October 2014 it had roughly 100,000 U.S. participants, said John S. Brownstein, Ph.D., an epidemiologist at Harvard Medical School in Boston and cofounder of Flu Near You.
That level is large enough to provide meaningful information, according to Matthew Biggerstaff, an epidemiologist at the Centers for Disease Control and Prevention in Atlanta, as well as other public health officials.
“We’ve been really excited at CDC about Flu Near You because it gives us a view of influenza illness that goes beyond the medically attended cases we base our usual surveillance on,” said Matthew Biggerstaff, an epidemiologist in the CDC’s influenza division. “It adds timeliness because we usually have a 1-week lag” in reporting data from outpatient physician visits and hospitalizations. Flu Near You, which asks participants to report weekly on whether they have any of 10 symptoms gives information that goes beyond the flu-like illness tallied by standard CDC surveillance. “We do not think that it will replace our traditional health care–based surveillance, but it gives us another set of data to look at,” Mr. Biggerstaff said in an interview.
The 10 symptoms that Flu Near You prompts users to report on each week are fever, cough, sore throat, shortness of breath, chills or night sweats, fatigue, nausea and vomiting, diarrhea, body ache, and headache. New participants are also asked whether they received a flu shot during the prior season, Aug. 1-July 31, as well as during the current season since the most recent July 31.
Flu Near You and other participatory surveillance tools also offer epidemiologists a way to track the participating cohort over time. That allows assessment of individual attack rates of influenza-like illness and other syndromes and also vaccine efficacy, Mr. Biggerstaff noted.
“It helps give us a feel for what is happening” with influenza. “We have worked with Flu Near You in the past and we continue to think about ways to work together on digital disease surveillance. We promote it to our state and local colleagues. We think it is a good resource for states to have,” he sad. The CDC’s influenza division is also assessing and using other novel forms of surveillance data, such as influenza and flu mentions on Twitter and searches on Google as well as a statistic Google maintains as Flu Trends.
Participatory surveillance is “very exciting” but is also “new and unproven and remains an experiment,” said Dr. Lawrence C. Madoff, director of the division of epidemiology and immunization at the Massachusetts Department of Public Health in Boston. But while participatory surveillance must still prove its role, U.S. public health officials “increasingly” accept the value of data from tools like Flu Near You, Dr. Madoff said in an interview. He cited the endorsement that participatory surveillance received in recent surveillance and early-detection recommendations from the World Health Organization. The 100,000 participants in Flu Near You give it a “critical mass that will become even more robust as it continues to grow,” Dr. Madoff said.
Further growth is clearly a priority for Flu Near You. “We’re now very excited to promote Flu Near You in a big way to try to get more numbers there and see if we can have a faster system for picking up influenza,” said Dr. Mark S. Smolinski, director of global health at Skoll.
“We are still trying to think through how do we get [Flu Near You] into the general consciousness” of more Americans, said Dr. Brownstein. While participants, not all of whom are active every week, provide enough data to show good correlation with the CDC’s routine surveillance on a national scale, if Flu Near You “had enough numbers we could drill down into subpopulations,” he noted. For now, the volume of participation makes subgroups too scanty in size for meaningful analysis, Dr. Brownstein conceded.
Mass gathering surveillance in Brazil
The Brazilian surveillance program at the World Cup was modeled on Flu Near You, but Dr. Libel, Dr. Smolinski, and their collaborators produced the app in about 8 weeks after receiving very short notice of the Brazilians’ interest. The weekly, symptom surveillance questions posed by the app replicated seven symptoms from Flu Near You – fever, cough, sore throat, shortness of breath, nausea and vomiting, diarrhea, and headache – and added three new symptoms to the survey: joint pain, bleeding, and red spots on body. This allowed the Health Ministry to also monitor for outbreaks of other infections including measles, cholera, dengue, and chikungunya, Dr. Libel said. The Brazilian app also asked participants each week whether they had been in contact with anyone who had any of the 10 listed symptoms, and whether they had looked for health care services. No outbreaks of any type occurred in Brazil during the World Cup, but during the period it was actively used 27% of the frequent respondents reported experiencing at least one symptom.
The first Brazilian effort “was basically a pilot program,” with little advance promotion, Dr. Smolinksi said in an interview. Officials of the Brazilian Ministry of Health were “impressed” with the data collected. They also liked the ability of the system to push out information on health care access to registered users, and the potential the app offered to send out urgent public health messages. “What the Health Ministry loved the most was that if there had been an outbreak they could have immediately reached out to fans,” Dr. Smolinski said.
The Ministry has interest in expanded surveillance and outreach programs for Carnival and the 2016 Summer Olympics, and Dr. Smolinski and his associates are hopeful that the International Olympics Committee will be receptive to the program and aid in its promotion during 2016. They are also planning to expand beyond smart phones and include the capability to interact with users via text and voice messages.
“We hope we will have huge numbers at the Olympics,” to better document the role participatory surveillance can play at mass gatherings, Dr. Smolinski said.
Dr. Libel, Dr. Brownstein, Mr. Biggerstaff, Dr. Smolinski, and Dr. Madoff had no disclosures.
On Twitter @mitchelzoler
VIENNA – Participatory surveillance has begun to enter mainstream public health.
The Brazilian Ministry of Health arranged for distribution of a participatory surveillance app for monitoring 10 symptoms in people attending or working at 2014 FIFA World Cup events. The smart phone app had 9,434 downloads, 7,155 registered users, and 4,706 active users who sent a message about their symptom status at least three times during the World Cup last June and July in Brazil, Dr. Marlo Libel said at the International Meeting on Emerging Diseases and Surveillance. “Healthy Cup 2014” became the first participatory surveillance tool ever used at a mass gathering event, he said.
“We demonstrated that direct self-reporting during a short period of time could be an excellent tool to complement other surveillance activities,” said Dr. Libel, a medical epidemiology consultant who worked with the Skoll Global Threats Fund on the Brazilian project. Officials at the Brazilian Ministry of Health were so pleased with the program that they are planning with Skoll to release similar apps for Carnival in Feb. 2015 and then for the 2016 Summer Olympics, Dr. Libel said.
Flu Near You shows U.S. growth
Longer-term participatory surveillance of U.S. residents began with the launch of the Flu Near You program in 2012, and by October 2014 it had roughly 100,000 U.S. participants, said John S. Brownstein, Ph.D., an epidemiologist at Harvard Medical School in Boston and cofounder of Flu Near You.
That level is large enough to provide meaningful information, according to Matthew Biggerstaff, an epidemiologist at the Centers for Disease Control and Prevention in Atlanta, as well as other public health officials.
“We’ve been really excited at CDC about Flu Near You because it gives us a view of influenza illness that goes beyond the medically attended cases we base our usual surveillance on,” said Matthew Biggerstaff, an epidemiologist in the CDC’s influenza division. “It adds timeliness because we usually have a 1-week lag” in reporting data from outpatient physician visits and hospitalizations. Flu Near You, which asks participants to report weekly on whether they have any of 10 symptoms gives information that goes beyond the flu-like illness tallied by standard CDC surveillance. “We do not think that it will replace our traditional health care–based surveillance, but it gives us another set of data to look at,” Mr. Biggerstaff said in an interview.
The 10 symptoms that Flu Near You prompts users to report on each week are fever, cough, sore throat, shortness of breath, chills or night sweats, fatigue, nausea and vomiting, diarrhea, body ache, and headache. New participants are also asked whether they received a flu shot during the prior season, Aug. 1-July 31, as well as during the current season since the most recent July 31.
Flu Near You and other participatory surveillance tools also offer epidemiologists a way to track the participating cohort over time. That allows assessment of individual attack rates of influenza-like illness and other syndromes and also vaccine efficacy, Mr. Biggerstaff noted.
“It helps give us a feel for what is happening” with influenza. “We have worked with Flu Near You in the past and we continue to think about ways to work together on digital disease surveillance. We promote it to our state and local colleagues. We think it is a good resource for states to have,” he sad. The CDC’s influenza division is also assessing and using other novel forms of surveillance data, such as influenza and flu mentions on Twitter and searches on Google as well as a statistic Google maintains as Flu Trends.
Participatory surveillance is “very exciting” but is also “new and unproven and remains an experiment,” said Dr. Lawrence C. Madoff, director of the division of epidemiology and immunization at the Massachusetts Department of Public Health in Boston. But while participatory surveillance must still prove its role, U.S. public health officials “increasingly” accept the value of data from tools like Flu Near You, Dr. Madoff said in an interview. He cited the endorsement that participatory surveillance received in recent surveillance and early-detection recommendations from the World Health Organization. The 100,000 participants in Flu Near You give it a “critical mass that will become even more robust as it continues to grow,” Dr. Madoff said.
Further growth is clearly a priority for Flu Near You. “We’re now very excited to promote Flu Near You in a big way to try to get more numbers there and see if we can have a faster system for picking up influenza,” said Dr. Mark S. Smolinski, director of global health at Skoll.
“We are still trying to think through how do we get [Flu Near You] into the general consciousness” of more Americans, said Dr. Brownstein. While participants, not all of whom are active every week, provide enough data to show good correlation with the CDC’s routine surveillance on a national scale, if Flu Near You “had enough numbers we could drill down into subpopulations,” he noted. For now, the volume of participation makes subgroups too scanty in size for meaningful analysis, Dr. Brownstein conceded.
Mass gathering surveillance in Brazil
The Brazilian surveillance program at the World Cup was modeled on Flu Near You, but Dr. Libel, Dr. Smolinski, and their collaborators produced the app in about 8 weeks after receiving very short notice of the Brazilians’ interest. The weekly, symptom surveillance questions posed by the app replicated seven symptoms from Flu Near You – fever, cough, sore throat, shortness of breath, nausea and vomiting, diarrhea, and headache – and added three new symptoms to the survey: joint pain, bleeding, and red spots on body. This allowed the Health Ministry to also monitor for outbreaks of other infections including measles, cholera, dengue, and chikungunya, Dr. Libel said. The Brazilian app also asked participants each week whether they had been in contact with anyone who had any of the 10 listed symptoms, and whether they had looked for health care services. No outbreaks of any type occurred in Brazil during the World Cup, but during the period it was actively used 27% of the frequent respondents reported experiencing at least one symptom.
The first Brazilian effort “was basically a pilot program,” with little advance promotion, Dr. Smolinksi said in an interview. Officials of the Brazilian Ministry of Health were “impressed” with the data collected. They also liked the ability of the system to push out information on health care access to registered users, and the potential the app offered to send out urgent public health messages. “What the Health Ministry loved the most was that if there had been an outbreak they could have immediately reached out to fans,” Dr. Smolinski said.
The Ministry has interest in expanded surveillance and outreach programs for Carnival and the 2016 Summer Olympics, and Dr. Smolinski and his associates are hopeful that the International Olympics Committee will be receptive to the program and aid in its promotion during 2016. They are also planning to expand beyond smart phones and include the capability to interact with users via text and voice messages.
“We hope we will have huge numbers at the Olympics,” to better document the role participatory surveillance can play at mass gatherings, Dr. Smolinski said.
Dr. Libel, Dr. Brownstein, Mr. Biggerstaff, Dr. Smolinski, and Dr. Madoff had no disclosures.
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM IMED 2014
Evidence Builds For Risk-based Antihypertension Guidelines
CHICAGO – The next time the U.S. hypertension management guideline gets revised, possibly within another couple of years, it may abandon the current approach of focusing primarily on a person’s blood pressure numbers and center instead on assessing a patient’s overall cardiovascular risk and using that status to guide the need for antihypertensive treatment and how aggressively it is applied.
In short, what some preventive cardiologists see coming down the pike is a blood pressure management guideline that follows the same path carved by the cholesterol management guideline issued by the American College of Cardiology and American Heart Association in 2013 (Circulation 2014 [doi: 10.1161/01.cir.0000437738.63853.7a]) that linked use of lipid-lowering treatment with a statin mostly to a patient’s atherosclerotic cardiovascular disease (ASCVD) risk rather than to their level of LDL cholesterol.
One example of the evidence driving this revisionist approach to thinking about hypertension definition came in a report at the American Heart Association Scientific Sessions that showed “a blood pressure treatment strategy focused just on blood pressure leaves substantial CVD risk unaddressed,” said Dr. Kunal N. Karmali, a cardiologist at Northwestern University, Chicago. “Multivariate risk estimation may help identify types of individuals who are likely to benefit from risk-reducing therapy across the spectrum of blood pressure.”
Dr. Karmali and his associates ran their analysis using data from two well-defined U.S. population data bases that included long-term follow-up, the Atherosclerosis Risk in Communities study and the Framingham Offspring Study, which together provided data for 18,898 people. The researchers categorized these people by their baseline systolic blood pressures into six groups, from below 120 mm Hg to 160 mm Hg and above, and calculated each person’s risk for an incident ASCVD event according to their baseline ASCVD risk score using the risk calculator that accompanied release of the 2013 cholesterol management guidelines. By subtracting the baseline risk–derived prediction of the CVD event rate from the actual number of events during follow-up, Dr. Karmali’s group came up with an estimate of the level of “excess” risk for people within each 10 mm Hg blood pressure stratum.
Ten-year follow-up of the two cohorts identified 739 ASCVD events, of which more than 500 were “excess;” the people in the two cohorts had substantially more ASCVD events than would have been predicted by their risk factors alone. These excess events occurred at all levels of blood pressure. The 6,656 people with baseline systolic blood pressures of 120-139 mm Hg, 35% of the people included in the study, had 45% of the excess events, Dr. Karmali reported.
While people with blood pressures of 120-139 mm Hg would generally not be candidates for antihypertensive treatment based on the existing U.S. guideline (JAMA 2014;311[5]:507-20), a sizable majority, 73%, had high baseline ASCVD risk levels, with predicted 10-year CVD rates of 7.5% or greater.
“An implication of this finding is to think beyond just blood pressure,” Dr. Karmali said. “You need to consider multiple risk factors and use overall risk assessment to inform your management decisions. Looking at just the single risk factor of blood pressure doesn’t capture the true benefits of treatment and weigh that against the risks from treatment,” he said in an interview.
He gave the example of an otherwise healthy woman aged 40 years with a systolic blood pressure of 142 mm Hg, who clearly has a different 10-year risk level than a man aged 70 years who has diabetes and smokes and also has a systolic pressure of 142 mm Hg.
“For cholesterol, we now direct our interventions at people who are at the highest risk, but for blood pressure we still focus on just the single number. Multivariate risk assessment would allow us to direct the interventions at the people who are more likely to benefit,” Dr. Kamali said.
Other recent analyses have also supported this approach, he noted. For example, a metaanalysis published in August used data from nearly 52,000 people collected in 11 studies to show that blood pressure–lowering treatment had a very similar impact on reducing future cardiovascular disease events regardless of a person’s baseline cardiovascular risk level (Lancet 2014;384:591-8).
For middle-aged adults and older people, “I think we would become much more efficient in our selection of people with modestly elevated blood pressure [who need drug treatment] by considering their global risk,” said Dr. Donald M. Lloyd-Jones, professor and chairman of preventive medicine at Northwestern University, and a collaborator on Dr. Karmali’s study.
Another advantage of a risk-based approach to blood pressure management over a number-based approach is that “putting blood pressure into the global context of risk makes me think about global risk management, and that is where clinicians need to move,” Dr. Lloyd-Jones said in an interview. “It’s not just, ‘get a number, treat it, and you’re done.’ You need to also think about statin treatment.”
He acknowledged the need for some caution in this approach, such as recognizing that blood pressure must be carefully reduced in, for example, people with a systolic pressure of 120-129 mm Hg so that blood pressure is not reduced to a dangerously low level (unlike cholesterol, which so far has not shown been shown to cause problems when reduced to very low levels). He also noted that a young adult with a fairly high systolic pressure of, say, 160 mm Hg should receive antihypertensive treatment even if the person has an otherwise low ASCVD risk. But in general a risk-based approach should provide better patient care, he said.
“If this is where new hypertension management guidelines go it would be a significant change,” Dr. Lloyd-Jones acknowledged, “but I think it would help patients. I think this approach merits real consideration” by the panel that will soon create the next revision to the U.S. hypertension management guideline.
The concept of a risk-based approach to diagnosing and managing patients with hypertension is ready for more thought among U.S. physicians and policy makers. It is very logical that we could prevent more events by focusing on people who are at higher risk for cardiovascular disease events, and there is more to risk reduction than just treating to a certain blood pressure level.
This approach to managing hypertension has been in place in New Zealand for at least a decade, and was woven into the 2013 hypertension management guidelines issued by the European Society of Cardiology (Eur. Heart J. 2013;34:2159-2219). There was also some attention given to the concept in the JNC VI U.S. hypertension guidelines, but then the guidelines panels backed away from it in the next two revisions.
|
| Mitchel L. Zoler/Frontline Medical News Dr. David C. Goff Jr. |
Several lines of evidence support the risk-based approach. In addition to Dr. Karmali’s new report, there was an analysis published in August that sowed the relative risk reduction from reducing blood pressure was similar across a range of risk levels (Lancet 2014;384:591-8). And a 2011 analysis showed that if you prioritize antihypertensive treatment based on risk level rather than just on systolic pressure you could treat the same number of people but prevent far more cardiovascular disease events (Ann. Int. Med. 2011;154:627-34).
These two prior reports, Dr. Karmali’s new study, and the change in approach introduced by guidelines in New Zealand and in Europe make it the right time to give this approach serious consideration by U.S. policy makers. I think many people agree it makes sense to focus attention on people with the highest cardiovascular risk. But a significant outstanding issue is whether clinicians will be willing to withhold blood pressure lowering treatment from selected people with systolic blood pressures above 140 mm Hg.
Dr. David C. Goff Jr., dean and professor of epidemiology at the Colorado School of Public Health, Aurora, made these comments in an interview. He had no disclosures.
The concept of a risk-based approach to diagnosing and managing patients with hypertension is ready for more thought among U.S. physicians and policy makers. It is very logical that we could prevent more events by focusing on people who are at higher risk for cardiovascular disease events, and there is more to risk reduction than just treating to a certain blood pressure level.
This approach to managing hypertension has been in place in New Zealand for at least a decade, and was woven into the 2013 hypertension management guidelines issued by the European Society of Cardiology (Eur. Heart J. 2013;34:2159-2219). There was also some attention given to the concept in the JNC VI U.S. hypertension guidelines, but then the guidelines panels backed away from it in the next two revisions.
|
|
| Mitchel L. Zoler/Frontline Medical News Dr. David C. Goff Jr. |
Several lines of evidence support the risk-based approach. In addition to Dr. Karmali’s new report, there was an analysis published in August that sowed the relative risk reduction from reducing blood pressure was similar across a range of risk levels (Lancet 2014;384:591-8). And a 2011 analysis showed that if you prioritize antihypertensive treatment based on risk level rather than just on systolic pressure you could treat the same number of people but prevent far more cardiovascular disease events (Ann. Int. Med. 2011;154:627-34).
These two prior reports, Dr. Karmali’s new study, and the change in approach introduced by guidelines in New Zealand and in Europe make it the right time to give this approach serious consideration by U.S. policy makers. I think many people agree it makes sense to focus attention on people with the highest cardiovascular risk. But a significant outstanding issue is whether clinicians will be willing to withhold blood pressure lowering treatment from selected people with systolic blood pressures above 140 mm Hg.
Dr. David C. Goff Jr., dean and professor of epidemiology at the Colorado School of Public Health, Aurora, made these comments in an interview. He had no disclosures.
The concept of a risk-based approach to diagnosing and managing patients with hypertension is ready for more thought among U.S. physicians and policy makers. It is very logical that we could prevent more events by focusing on people who are at higher risk for cardiovascular disease events, and there is more to risk reduction than just treating to a certain blood pressure level.
This approach to managing hypertension has been in place in New Zealand for at least a decade, and was woven into the 2013 hypertension management guidelines issued by the European Society of Cardiology (Eur. Heart J. 2013;34:2159-2219). There was also some attention given to the concept in the JNC VI U.S. hypertension guidelines, but then the guidelines panels backed away from it in the next two revisions.
|
|
| Mitchel L. Zoler/Frontline Medical News Dr. David C. Goff Jr. |
Several lines of evidence support the risk-based approach. In addition to Dr. Karmali’s new report, there was an analysis published in August that sowed the relative risk reduction from reducing blood pressure was similar across a range of risk levels (Lancet 2014;384:591-8). And a 2011 analysis showed that if you prioritize antihypertensive treatment based on risk level rather than just on systolic pressure you could treat the same number of people but prevent far more cardiovascular disease events (Ann. Int. Med. 2011;154:627-34).
These two prior reports, Dr. Karmali’s new study, and the change in approach introduced by guidelines in New Zealand and in Europe make it the right time to give this approach serious consideration by U.S. policy makers. I think many people agree it makes sense to focus attention on people with the highest cardiovascular risk. But a significant outstanding issue is whether clinicians will be willing to withhold blood pressure lowering treatment from selected people with systolic blood pressures above 140 mm Hg.
Dr. David C. Goff Jr., dean and professor of epidemiology at the Colorado School of Public Health, Aurora, made these comments in an interview. He had no disclosures.
CHICAGO – The next time the U.S. hypertension management guideline gets revised, possibly within another couple of years, it may abandon the current approach of focusing primarily on a person’s blood pressure numbers and center instead on assessing a patient’s overall cardiovascular risk and using that status to guide the need for antihypertensive treatment and how aggressively it is applied.
In short, what some preventive cardiologists see coming down the pike is a blood pressure management guideline that follows the same path carved by the cholesterol management guideline issued by the American College of Cardiology and American Heart Association in 2013 (Circulation 2014 [doi: 10.1161/01.cir.0000437738.63853.7a]) that linked use of lipid-lowering treatment with a statin mostly to a patient’s atherosclerotic cardiovascular disease (ASCVD) risk rather than to their level of LDL cholesterol.
One example of the evidence driving this revisionist approach to thinking about hypertension definition came in a report at the American Heart Association Scientific Sessions that showed “a blood pressure treatment strategy focused just on blood pressure leaves substantial CVD risk unaddressed,” said Dr. Kunal N. Karmali, a cardiologist at Northwestern University, Chicago. “Multivariate risk estimation may help identify types of individuals who are likely to benefit from risk-reducing therapy across the spectrum of blood pressure.”
Dr. Karmali and his associates ran their analysis using data from two well-defined U.S. population data bases that included long-term follow-up, the Atherosclerosis Risk in Communities study and the Framingham Offspring Study, which together provided data for 18,898 people. The researchers categorized these people by their baseline systolic blood pressures into six groups, from below 120 mm Hg to 160 mm Hg and above, and calculated each person’s risk for an incident ASCVD event according to their baseline ASCVD risk score using the risk calculator that accompanied release of the 2013 cholesterol management guidelines. By subtracting the baseline risk–derived prediction of the CVD event rate from the actual number of events during follow-up, Dr. Karmali’s group came up with an estimate of the level of “excess” risk for people within each 10 mm Hg blood pressure stratum.
Ten-year follow-up of the two cohorts identified 739 ASCVD events, of which more than 500 were “excess;” the people in the two cohorts had substantially more ASCVD events than would have been predicted by their risk factors alone. These excess events occurred at all levels of blood pressure. The 6,656 people with baseline systolic blood pressures of 120-139 mm Hg, 35% of the people included in the study, had 45% of the excess events, Dr. Karmali reported.
While people with blood pressures of 120-139 mm Hg would generally not be candidates for antihypertensive treatment based on the existing U.S. guideline (JAMA 2014;311[5]:507-20), a sizable majority, 73%, had high baseline ASCVD risk levels, with predicted 10-year CVD rates of 7.5% or greater.
“An implication of this finding is to think beyond just blood pressure,” Dr. Karmali said. “You need to consider multiple risk factors and use overall risk assessment to inform your management decisions. Looking at just the single risk factor of blood pressure doesn’t capture the true benefits of treatment and weigh that against the risks from treatment,” he said in an interview.
He gave the example of an otherwise healthy woman aged 40 years with a systolic blood pressure of 142 mm Hg, who clearly has a different 10-year risk level than a man aged 70 years who has diabetes and smokes and also has a systolic pressure of 142 mm Hg.
“For cholesterol, we now direct our interventions at people who are at the highest risk, but for blood pressure we still focus on just the single number. Multivariate risk assessment would allow us to direct the interventions at the people who are more likely to benefit,” Dr. Kamali said.
Other recent analyses have also supported this approach, he noted. For example, a metaanalysis published in August used data from nearly 52,000 people collected in 11 studies to show that blood pressure–lowering treatment had a very similar impact on reducing future cardiovascular disease events regardless of a person’s baseline cardiovascular risk level (Lancet 2014;384:591-8).
For middle-aged adults and older people, “I think we would become much more efficient in our selection of people with modestly elevated blood pressure [who need drug treatment] by considering their global risk,” said Dr. Donald M. Lloyd-Jones, professor and chairman of preventive medicine at Northwestern University, and a collaborator on Dr. Karmali’s study.
Another advantage of a risk-based approach to blood pressure management over a number-based approach is that “putting blood pressure into the global context of risk makes me think about global risk management, and that is where clinicians need to move,” Dr. Lloyd-Jones said in an interview. “It’s not just, ‘get a number, treat it, and you’re done.’ You need to also think about statin treatment.”
He acknowledged the need for some caution in this approach, such as recognizing that blood pressure must be carefully reduced in, for example, people with a systolic pressure of 120-129 mm Hg so that blood pressure is not reduced to a dangerously low level (unlike cholesterol, which so far has not shown been shown to cause problems when reduced to very low levels). He also noted that a young adult with a fairly high systolic pressure of, say, 160 mm Hg should receive antihypertensive treatment even if the person has an otherwise low ASCVD risk. But in general a risk-based approach should provide better patient care, he said.
“If this is where new hypertension management guidelines go it would be a significant change,” Dr. Lloyd-Jones acknowledged, “but I think it would help patients. I think this approach merits real consideration” by the panel that will soon create the next revision to the U.S. hypertension management guideline.
CHICAGO – The next time the U.S. hypertension management guideline gets revised, possibly within another couple of years, it may abandon the current approach of focusing primarily on a person’s blood pressure numbers and center instead on assessing a patient’s overall cardiovascular risk and using that status to guide the need for antihypertensive treatment and how aggressively it is applied.
In short, what some preventive cardiologists see coming down the pike is a blood pressure management guideline that follows the same path carved by the cholesterol management guideline issued by the American College of Cardiology and American Heart Association in 2013 (Circulation 2014 [doi: 10.1161/01.cir.0000437738.63853.7a]) that linked use of lipid-lowering treatment with a statin mostly to a patient’s atherosclerotic cardiovascular disease (ASCVD) risk rather than to their level of LDL cholesterol.
One example of the evidence driving this revisionist approach to thinking about hypertension definition came in a report at the American Heart Association Scientific Sessions that showed “a blood pressure treatment strategy focused just on blood pressure leaves substantial CVD risk unaddressed,” said Dr. Kunal N. Karmali, a cardiologist at Northwestern University, Chicago. “Multivariate risk estimation may help identify types of individuals who are likely to benefit from risk-reducing therapy across the spectrum of blood pressure.”
Dr. Karmali and his associates ran their analysis using data from two well-defined U.S. population data bases that included long-term follow-up, the Atherosclerosis Risk in Communities study and the Framingham Offspring Study, which together provided data for 18,898 people. The researchers categorized these people by their baseline systolic blood pressures into six groups, from below 120 mm Hg to 160 mm Hg and above, and calculated each person’s risk for an incident ASCVD event according to their baseline ASCVD risk score using the risk calculator that accompanied release of the 2013 cholesterol management guidelines. By subtracting the baseline risk–derived prediction of the CVD event rate from the actual number of events during follow-up, Dr. Karmali’s group came up with an estimate of the level of “excess” risk for people within each 10 mm Hg blood pressure stratum.
Ten-year follow-up of the two cohorts identified 739 ASCVD events, of which more than 500 were “excess;” the people in the two cohorts had substantially more ASCVD events than would have been predicted by their risk factors alone. These excess events occurred at all levels of blood pressure. The 6,656 people with baseline systolic blood pressures of 120-139 mm Hg, 35% of the people included in the study, had 45% of the excess events, Dr. Karmali reported.
While people with blood pressures of 120-139 mm Hg would generally not be candidates for antihypertensive treatment based on the existing U.S. guideline (JAMA 2014;311[5]:507-20), a sizable majority, 73%, had high baseline ASCVD risk levels, with predicted 10-year CVD rates of 7.5% or greater.
“An implication of this finding is to think beyond just blood pressure,” Dr. Karmali said. “You need to consider multiple risk factors and use overall risk assessment to inform your management decisions. Looking at just the single risk factor of blood pressure doesn’t capture the true benefits of treatment and weigh that against the risks from treatment,” he said in an interview.
He gave the example of an otherwise healthy woman aged 40 years with a systolic blood pressure of 142 mm Hg, who clearly has a different 10-year risk level than a man aged 70 years who has diabetes and smokes and also has a systolic pressure of 142 mm Hg.
“For cholesterol, we now direct our interventions at people who are at the highest risk, but for blood pressure we still focus on just the single number. Multivariate risk assessment would allow us to direct the interventions at the people who are more likely to benefit,” Dr. Kamali said.
Other recent analyses have also supported this approach, he noted. For example, a metaanalysis published in August used data from nearly 52,000 people collected in 11 studies to show that blood pressure–lowering treatment had a very similar impact on reducing future cardiovascular disease events regardless of a person’s baseline cardiovascular risk level (Lancet 2014;384:591-8).
For middle-aged adults and older people, “I think we would become much more efficient in our selection of people with modestly elevated blood pressure [who need drug treatment] by considering their global risk,” said Dr. Donald M. Lloyd-Jones, professor and chairman of preventive medicine at Northwestern University, and a collaborator on Dr. Karmali’s study.
Another advantage of a risk-based approach to blood pressure management over a number-based approach is that “putting blood pressure into the global context of risk makes me think about global risk management, and that is where clinicians need to move,” Dr. Lloyd-Jones said in an interview. “It’s not just, ‘get a number, treat it, and you’re done.’ You need to also think about statin treatment.”
He acknowledged the need for some caution in this approach, such as recognizing that blood pressure must be carefully reduced in, for example, people with a systolic pressure of 120-129 mm Hg so that blood pressure is not reduced to a dangerously low level (unlike cholesterol, which so far has not shown been shown to cause problems when reduced to very low levels). He also noted that a young adult with a fairly high systolic pressure of, say, 160 mm Hg should receive antihypertensive treatment even if the person has an otherwise low ASCVD risk. But in general a risk-based approach should provide better patient care, he said.
“If this is where new hypertension management guidelines go it would be a significant change,” Dr. Lloyd-Jones acknowledged, “but I think it would help patients. I think this approach merits real consideration” by the panel that will soon create the next revision to the U.S. hypertension management guideline.
AT THE AHA SCIENTIFIC SESSIONS
Evidence builds for risk-based antihypertension guidelines
CHICAGO – The next time the U.S. hypertension management guideline gets revised, possibly within another couple of years, it may abandon the current approach of focusing primarily on a person’s blood pressure numbers and center instead on assessing a patient’s overall cardiovascular risk and using that status to guide the need for antihypertensive treatment and how aggressively it is applied.
In short, what some preventive cardiologists see coming down the pike is a blood pressure management guideline that follows the same path carved by the cholesterol management guideline issued by the American College of Cardiology and American Heart Association in 2013 (Circulation 2014 [doi: 10.1161/01.cir.0000437738.63853.7a]) that linked use of lipid-lowering treatment with a statin mostly to a patient’s atherosclerotic cardiovascular disease (ASCVD) risk rather than to their level of LDL cholesterol.
One example of the evidence driving this revisionist approach to thinking about hypertension definition came in a report at the American Heart Association Scientific Sessions that showed “a blood pressure treatment strategy focused just on blood pressure leaves substantial CVD risk unaddressed,” said Dr. Kunal N. Karmali, a cardiologist at Northwestern University, Chicago. “Multivariate risk estimation may help identify types of individuals who are likely to benefit from risk-reducing therapy across the spectrum of blood pressure.”
Dr. Karmali and his associates ran their analysis using data from two well-defined U.S. population data bases that included long-term follow-up, the Atherosclerosis Risk in Communities study and the Framingham Offspring Study, which together provided data for 18,898 people. The researchers categorized these people by their baseline systolic blood pressures into six groups, from below 120 mm Hg to 160 mm Hg and above, and calculated each person’s risk for an incident ASCVD event according to their baseline ASCVD risk score using the risk calculator that accompanied release of the 2013 cholesterol management guidelines. By subtracting the baseline risk–derived prediction of the CVD event rate from the actual number of events during follow-up, Dr. Karmali’s group came up with an estimate of the level of “excess” risk for people within each 10 mm Hg blood pressure stratum.
Ten-year follow-up of the two cohorts identified 739 ASCVD events, of which more than 500 were “excess;” the people in the two cohorts had substantially more ASCVD events than would have been predicted by their risk factors alone. These excess events occurred at all levels of blood pressure. The 6,656 people with baseline systolic blood pressures of 120-139 mm Hg, 35% of the people included in the study, had 45% of the excess events, Dr. Karmali reported.
While people with blood pressures of 120-139 mm Hg would generally not be candidates for antihypertensive treatment based on the existing U.S. guideline (JAMA 2014;311[5]:507-20), a sizable majority, 73%, had high baseline ASCVD risk levels, with predicted 10-year CVD rates of 7.5% or greater.
“An implication of this finding is to think beyond just blood pressure,” Dr. Karmali said. “You need to consider multiple risk factors and use overall risk assessment to inform your management decisions. Looking at just the single risk factor of blood pressure doesn’t capture the true benefits of treatment and weigh that against the risks from treatment,” he said in an interview.
He gave the example of an otherwise healthy woman aged 40 years with a systolic blood pressure of 142 mm Hg, who clearly has a different 10-year risk level than a man aged 70 years who has diabetes and smokes and also has a systolic pressure of 142 mm Hg.
“For cholesterol, we now direct our interventions at people who are at the highest risk, but for blood pressure we still focus on just the single number. Multivariate risk assessment would allow us to direct the interventions at the people who are more likely to benefit,” Dr. Kamali said.
Other recent analyses have also supported this approach, he noted. For example, a metaanalysis published in August used data from nearly 52,000 people collected in 11 studies to show that blood pressure–lowering treatment had a very similar impact on reducing future cardiovascular disease events regardless of a person’s baseline cardiovascular risk level (Lancet 2014;384:591-8).
For middle-aged adults and older people, “I think we would become much more efficient in our selection of people with modestly elevated blood pressure [who need drug treatment] by considering their global risk,” said Dr. Donald M. Lloyd-Jones, professor and chairman of preventive medicine at Northwestern University, and a collaborator on Dr. Karmali’s study.
Another advantage of a risk-based approach to blood pressure management over a number-based approach is that “putting blood pressure into the global context of risk makes me think about global risk management, and that is where clinicians need to move,” Dr. Lloyd-Jones said in an interview. “It’s not just, ‘get a number, treat it, and you’re done.’ You need to also think about statin treatment.”
He acknowledged the need for some caution in this approach, such as recognizing that blood pressure must be carefully reduced in, for example, people with a systolic pressure of 120-129 mm Hg so that blood pressure is not reduced to a dangerously low level (unlike cholesterol, which so far has not shown been shown to cause problems when reduced to very low levels). He also noted that a young adult with a fairly high systolic pressure of, say, 160 mm Hg should receive antihypertensive treatment even if the person has an otherwise low ASCVD risk. But in general a risk-based approach should provide better patient care, he said.
“If this is where new hypertension management guidelines go it would be a significant change,” Dr. Lloyd-Jones acknowledged, “but I think it would help patients. I think this approach merits real consideration” by the panel that will soon create the next revision to the U.S. hypertension management guideline.
On Twitter @mitchelzoler
The concept of a risk-based approach to diagnosing and managing patients with hypertension is ready for more thought among U.S. physicians and policy makers. It is very logical that we could prevent more events by focusing on people who are at higher risk for cardiovascular disease events, and there is more to risk reduction than just treating to a certain blood pressure level.
This approach to managing hypertension has been in place in New Zealand for at least a decade, and was woven into the 2013 hypertension management guidelines issued by the European Society of Cardiology (Eur. Heart J. 2013;34:2159-2219). There was also some attention given to the concept in the JNC VI U.S. hypertension guidelines, but then the guidelines panels backed away from it in the next two revisions.
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| Mitchel L. Zoler/Frontline Medical News Dr. David C. Goff Jr. |
Several lines of evidence support the risk-based approach. In addition to Dr. Karmali’s new report, there was an analysis published in August that sowed the relative risk reduction from reducing blood pressure was similar across a range of risk levels (Lancet 2014;384:591-8). And a 2011 analysis showed that if you prioritize antihypertensive treatment based on risk level rather than just on systolic pressure you could treat the same number of people but prevent far more cardiovascular disease events (Ann. Int. Med. 2011;154:627-34).
These two prior reports, Dr. Karmali’s new study, and the change in approach introduced by guidelines in New Zealand and in Europe make it the right time to give this approach serious consideration by U.S. policy makers. I think many people agree it makes sense to focus attention on people with the highest cardiovascular risk. But a significant outstanding issue is whether clinicians will be willing to withhold blood pressure lowering treatment from selected people with systolic blood pressures above 140 mm Hg.
Dr. David C. Goff Jr., dean and professor of epidemiology at the Colorado School of Public Health, Aurora, made these comments in an interview. He had no disclosures.
The concept of a risk-based approach to diagnosing and managing patients with hypertension is ready for more thought among U.S. physicians and policy makers. It is very logical that we could prevent more events by focusing on people who are at higher risk for cardiovascular disease events, and there is more to risk reduction than just treating to a certain blood pressure level.
This approach to managing hypertension has been in place in New Zealand for at least a decade, and was woven into the 2013 hypertension management guidelines issued by the European Society of Cardiology (Eur. Heart J. 2013;34:2159-2219). There was also some attention given to the concept in the JNC VI U.S. hypertension guidelines, but then the guidelines panels backed away from it in the next two revisions.
|
|
| Mitchel L. Zoler/Frontline Medical News Dr. David C. Goff Jr. |
Several lines of evidence support the risk-based approach. In addition to Dr. Karmali’s new report, there was an analysis published in August that sowed the relative risk reduction from reducing blood pressure was similar across a range of risk levels (Lancet 2014;384:591-8). And a 2011 analysis showed that if you prioritize antihypertensive treatment based on risk level rather than just on systolic pressure you could treat the same number of people but prevent far more cardiovascular disease events (Ann. Int. Med. 2011;154:627-34).
These two prior reports, Dr. Karmali’s new study, and the change in approach introduced by guidelines in New Zealand and in Europe make it the right time to give this approach serious consideration by U.S. policy makers. I think many people agree it makes sense to focus attention on people with the highest cardiovascular risk. But a significant outstanding issue is whether clinicians will be willing to withhold blood pressure lowering treatment from selected people with systolic blood pressures above 140 mm Hg.
Dr. David C. Goff Jr., dean and professor of epidemiology at the Colorado School of Public Health, Aurora, made these comments in an interview. He had no disclosures.
The concept of a risk-based approach to diagnosing and managing patients with hypertension is ready for more thought among U.S. physicians and policy makers. It is very logical that we could prevent more events by focusing on people who are at higher risk for cardiovascular disease events, and there is more to risk reduction than just treating to a certain blood pressure level.
This approach to managing hypertension has been in place in New Zealand for at least a decade, and was woven into the 2013 hypertension management guidelines issued by the European Society of Cardiology (Eur. Heart J. 2013;34:2159-2219). There was also some attention given to the concept in the JNC VI U.S. hypertension guidelines, but then the guidelines panels backed away from it in the next two revisions.
|
|
| Mitchel L. Zoler/Frontline Medical News Dr. David C. Goff Jr. |
Several lines of evidence support the risk-based approach. In addition to Dr. Karmali’s new report, there was an analysis published in August that sowed the relative risk reduction from reducing blood pressure was similar across a range of risk levels (Lancet 2014;384:591-8). And a 2011 analysis showed that if you prioritize antihypertensive treatment based on risk level rather than just on systolic pressure you could treat the same number of people but prevent far more cardiovascular disease events (Ann. Int. Med. 2011;154:627-34).
These two prior reports, Dr. Karmali’s new study, and the change in approach introduced by guidelines in New Zealand and in Europe make it the right time to give this approach serious consideration by U.S. policy makers. I think many people agree it makes sense to focus attention on people with the highest cardiovascular risk. But a significant outstanding issue is whether clinicians will be willing to withhold blood pressure lowering treatment from selected people with systolic blood pressures above 140 mm Hg.
Dr. David C. Goff Jr., dean and professor of epidemiology at the Colorado School of Public Health, Aurora, made these comments in an interview. He had no disclosures.
CHICAGO – The next time the U.S. hypertension management guideline gets revised, possibly within another couple of years, it may abandon the current approach of focusing primarily on a person’s blood pressure numbers and center instead on assessing a patient’s overall cardiovascular risk and using that status to guide the need for antihypertensive treatment and how aggressively it is applied.
In short, what some preventive cardiologists see coming down the pike is a blood pressure management guideline that follows the same path carved by the cholesterol management guideline issued by the American College of Cardiology and American Heart Association in 2013 (Circulation 2014 [doi: 10.1161/01.cir.0000437738.63853.7a]) that linked use of lipid-lowering treatment with a statin mostly to a patient’s atherosclerotic cardiovascular disease (ASCVD) risk rather than to their level of LDL cholesterol.
One example of the evidence driving this revisionist approach to thinking about hypertension definition came in a report at the American Heart Association Scientific Sessions that showed “a blood pressure treatment strategy focused just on blood pressure leaves substantial CVD risk unaddressed,” said Dr. Kunal N. Karmali, a cardiologist at Northwestern University, Chicago. “Multivariate risk estimation may help identify types of individuals who are likely to benefit from risk-reducing therapy across the spectrum of blood pressure.”
Dr. Karmali and his associates ran their analysis using data from two well-defined U.S. population data bases that included long-term follow-up, the Atherosclerosis Risk in Communities study and the Framingham Offspring Study, which together provided data for 18,898 people. The researchers categorized these people by their baseline systolic blood pressures into six groups, from below 120 mm Hg to 160 mm Hg and above, and calculated each person’s risk for an incident ASCVD event according to their baseline ASCVD risk score using the risk calculator that accompanied release of the 2013 cholesterol management guidelines. By subtracting the baseline risk–derived prediction of the CVD event rate from the actual number of events during follow-up, Dr. Karmali’s group came up with an estimate of the level of “excess” risk for people within each 10 mm Hg blood pressure stratum.
Ten-year follow-up of the two cohorts identified 739 ASCVD events, of which more than 500 were “excess;” the people in the two cohorts had substantially more ASCVD events than would have been predicted by their risk factors alone. These excess events occurred at all levels of blood pressure. The 6,656 people with baseline systolic blood pressures of 120-139 mm Hg, 35% of the people included in the study, had 45% of the excess events, Dr. Karmali reported.
While people with blood pressures of 120-139 mm Hg would generally not be candidates for antihypertensive treatment based on the existing U.S. guideline (JAMA 2014;311[5]:507-20), a sizable majority, 73%, had high baseline ASCVD risk levels, with predicted 10-year CVD rates of 7.5% or greater.
“An implication of this finding is to think beyond just blood pressure,” Dr. Karmali said. “You need to consider multiple risk factors and use overall risk assessment to inform your management decisions. Looking at just the single risk factor of blood pressure doesn’t capture the true benefits of treatment and weigh that against the risks from treatment,” he said in an interview.
He gave the example of an otherwise healthy woman aged 40 years with a systolic blood pressure of 142 mm Hg, who clearly has a different 10-year risk level than a man aged 70 years who has diabetes and smokes and also has a systolic pressure of 142 mm Hg.
“For cholesterol, we now direct our interventions at people who are at the highest risk, but for blood pressure we still focus on just the single number. Multivariate risk assessment would allow us to direct the interventions at the people who are more likely to benefit,” Dr. Kamali said.
Other recent analyses have also supported this approach, he noted. For example, a metaanalysis published in August used data from nearly 52,000 people collected in 11 studies to show that blood pressure–lowering treatment had a very similar impact on reducing future cardiovascular disease events regardless of a person’s baseline cardiovascular risk level (Lancet 2014;384:591-8).
For middle-aged adults and older people, “I think we would become much more efficient in our selection of people with modestly elevated blood pressure [who need drug treatment] by considering their global risk,” said Dr. Donald M. Lloyd-Jones, professor and chairman of preventive medicine at Northwestern University, and a collaborator on Dr. Karmali’s study.
Another advantage of a risk-based approach to blood pressure management over a number-based approach is that “putting blood pressure into the global context of risk makes me think about global risk management, and that is where clinicians need to move,” Dr. Lloyd-Jones said in an interview. “It’s not just, ‘get a number, treat it, and you’re done.’ You need to also think about statin treatment.”
He acknowledged the need for some caution in this approach, such as recognizing that blood pressure must be carefully reduced in, for example, people with a systolic pressure of 120-129 mm Hg so that blood pressure is not reduced to a dangerously low level (unlike cholesterol, which so far has not shown been shown to cause problems when reduced to very low levels). He also noted that a young adult with a fairly high systolic pressure of, say, 160 mm Hg should receive antihypertensive treatment even if the person has an otherwise low ASCVD risk. But in general a risk-based approach should provide better patient care, he said.
“If this is where new hypertension management guidelines go it would be a significant change,” Dr. Lloyd-Jones acknowledged, “but I think it would help patients. I think this approach merits real consideration” by the panel that will soon create the next revision to the U.S. hypertension management guideline.
On Twitter @mitchelzoler
CHICAGO – The next time the U.S. hypertension management guideline gets revised, possibly within another couple of years, it may abandon the current approach of focusing primarily on a person’s blood pressure numbers and center instead on assessing a patient’s overall cardiovascular risk and using that status to guide the need for antihypertensive treatment and how aggressively it is applied.
In short, what some preventive cardiologists see coming down the pike is a blood pressure management guideline that follows the same path carved by the cholesterol management guideline issued by the American College of Cardiology and American Heart Association in 2013 (Circulation 2014 [doi: 10.1161/01.cir.0000437738.63853.7a]) that linked use of lipid-lowering treatment with a statin mostly to a patient’s atherosclerotic cardiovascular disease (ASCVD) risk rather than to their level of LDL cholesterol.
One example of the evidence driving this revisionist approach to thinking about hypertension definition came in a report at the American Heart Association Scientific Sessions that showed “a blood pressure treatment strategy focused just on blood pressure leaves substantial CVD risk unaddressed,” said Dr. Kunal N. Karmali, a cardiologist at Northwestern University, Chicago. “Multivariate risk estimation may help identify types of individuals who are likely to benefit from risk-reducing therapy across the spectrum of blood pressure.”
Dr. Karmali and his associates ran their analysis using data from two well-defined U.S. population data bases that included long-term follow-up, the Atherosclerosis Risk in Communities study and the Framingham Offspring Study, which together provided data for 18,898 people. The researchers categorized these people by their baseline systolic blood pressures into six groups, from below 120 mm Hg to 160 mm Hg and above, and calculated each person’s risk for an incident ASCVD event according to their baseline ASCVD risk score using the risk calculator that accompanied release of the 2013 cholesterol management guidelines. By subtracting the baseline risk–derived prediction of the CVD event rate from the actual number of events during follow-up, Dr. Karmali’s group came up with an estimate of the level of “excess” risk for people within each 10 mm Hg blood pressure stratum.
Ten-year follow-up of the two cohorts identified 739 ASCVD events, of which more than 500 were “excess;” the people in the two cohorts had substantially more ASCVD events than would have been predicted by their risk factors alone. These excess events occurred at all levels of blood pressure. The 6,656 people with baseline systolic blood pressures of 120-139 mm Hg, 35% of the people included in the study, had 45% of the excess events, Dr. Karmali reported.
While people with blood pressures of 120-139 mm Hg would generally not be candidates for antihypertensive treatment based on the existing U.S. guideline (JAMA 2014;311[5]:507-20), a sizable majority, 73%, had high baseline ASCVD risk levels, with predicted 10-year CVD rates of 7.5% or greater.
“An implication of this finding is to think beyond just blood pressure,” Dr. Karmali said. “You need to consider multiple risk factors and use overall risk assessment to inform your management decisions. Looking at just the single risk factor of blood pressure doesn’t capture the true benefits of treatment and weigh that against the risks from treatment,” he said in an interview.
He gave the example of an otherwise healthy woman aged 40 years with a systolic blood pressure of 142 mm Hg, who clearly has a different 10-year risk level than a man aged 70 years who has diabetes and smokes and also has a systolic pressure of 142 mm Hg.
“For cholesterol, we now direct our interventions at people who are at the highest risk, but for blood pressure we still focus on just the single number. Multivariate risk assessment would allow us to direct the interventions at the people who are more likely to benefit,” Dr. Kamali said.
Other recent analyses have also supported this approach, he noted. For example, a metaanalysis published in August used data from nearly 52,000 people collected in 11 studies to show that blood pressure–lowering treatment had a very similar impact on reducing future cardiovascular disease events regardless of a person’s baseline cardiovascular risk level (Lancet 2014;384:591-8).
For middle-aged adults and older people, “I think we would become much more efficient in our selection of people with modestly elevated blood pressure [who need drug treatment] by considering their global risk,” said Dr. Donald M. Lloyd-Jones, professor and chairman of preventive medicine at Northwestern University, and a collaborator on Dr. Karmali’s study.
Another advantage of a risk-based approach to blood pressure management over a number-based approach is that “putting blood pressure into the global context of risk makes me think about global risk management, and that is where clinicians need to move,” Dr. Lloyd-Jones said in an interview. “It’s not just, ‘get a number, treat it, and you’re done.’ You need to also think about statin treatment.”
He acknowledged the need for some caution in this approach, such as recognizing that blood pressure must be carefully reduced in, for example, people with a systolic pressure of 120-129 mm Hg so that blood pressure is not reduced to a dangerously low level (unlike cholesterol, which so far has not shown been shown to cause problems when reduced to very low levels). He also noted that a young adult with a fairly high systolic pressure of, say, 160 mm Hg should receive antihypertensive treatment even if the person has an otherwise low ASCVD risk. But in general a risk-based approach should provide better patient care, he said.
“If this is where new hypertension management guidelines go it would be a significant change,” Dr. Lloyd-Jones acknowledged, “but I think it would help patients. I think this approach merits real consideration” by the panel that will soon create the next revision to the U.S. hypertension management guideline.
On Twitter @mitchelzoler
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point: Many people with systolic blood pressures of 120-139 mm Hg have significant cardiovascular disease risk that often goes untreated.
Major finding: People with a systolic blood pressure of 120-139 mm Hg generated 45% of excess cardiovascular disease events.
Data source: Analysis of 10-year outcomes of 18,898 American adults followed in either the ARIC study or in the Framingham Offspring Study.
Disclosures: Dr. Karmali and Dr. Lloyd-Jones had no disclosures.
Coronary stent patients need individualized DAPT duration
CHICAGO – Clinicians managing patients who have just received drug-eluting coronary stents need to individualize the duration of the antiplatelet therapy they prescribe and stop thinking that a single length of treatment works best for all patients, based on results from a trio of newly reported trials, as well as earlier study findings.
In general, the new findings seemed to show that following percutaneous coronary intervention (PCI) with a stent, patients with a low risk for stent thrombosis, myocardial infarction, or another type of ischemic event, as well as those with a high bleeding risk, fare best when their duration of dual antiplatelet therapy (DAPT) with aspirin plus a thienopyridine ends after 6 months, while patients with a low bleeding risk and a high risk for an ischemic event will usually do better when their DAPT continues well beyond 12 months, for 30 months and possibly longer.
“We now have results from 35,000 patients in randomized trials that addressed the question of duration of DAPT. We need to make up our minds, and it’s probably an individualized decision,” Dr. Gilles Montalescot said at the American Heart Association Scientific Sessions.
“The patients [in the three newly reported studies] were generally doing well, and so we are operating at the edge of competing risks” they face for ischemia and bleeding. “We need individualization of treatment, but what remains to be determined is, how do we make that decision? Who is more at risk for ischemic events and less at risk for bleeding, and who is more at risk for bleeding and less from ischemia?” commented Dr. Elliott M. Antman, professor of medicine and associate dean for clinical and translational research at Harvard University in Boston.
The DAPT trial
Drug-eluting stent recipients at increased risk for bleeding who are good candidates for a briefer, 6-month duration of DAPT include those with a history of a prior bleed, advanced age, pending need for surgery, patients who need anticoagulation treatment such as those with atrial fibrillation, patients with one or more comorbidities that put them at higher bleeding risk such as gastrointestinal disease or a history of stroke, and patients with a “nuisance” bleed, said Dr. Montalescot, a professor of cardiology at the University of Paris and director of the cardiac care unit at Pitié-Salpêtrière Hospital in Paris.
These conclusions emerged from a surge of new data from three studies presented at the meeting that all addressed DAPT duration following PCI.
Perhaps most noteworthy and anticipated were results from the Dual Antiplatelet Therapy study, a randomized trial that had its beginnings in 2006 when cardiologists first became alarmed by the potential risk from stent thrombosis associated with the use of first-generation DES, specifically the original sirolimus-eluting (Cypher) and paclitaxel-eluting (Taxus) models. At the urging of staffers at the Food and Drug Administration, a group of eight stent manufacturing companies and pharmaceutical companies joined together to sponsor the DAPT study, which started with nearly 23,000 patients who received a DES and, after their first year of DAPT treatment, whittled down to 9,961 patients who were eligible for randomization to either stop DAPT after 1 year or continue on DAPT for an additional 18 months (30 months total time on DAPT).
The results showed that this highly selected group of patients – who went through their first year on DAPT with no bleeding event, no ischemic event, and who were willing to be randomized – those assigned to 30 months of DAPT had a 1% absolute and 71% relative reduction in stent thrombosis, compared with patients who stopped DAPT after 12 months, and a 1.6% absolute and 29% relative reduction in their rate of major cardiovascular or cerebrovascular events, statistically significant differences for the study’s two primary endpoints. The reduction in major events was driven mainly by a 2% absolute reduction in the rate of myocardial infarctions, reported Dr. Laura Mauri at the meeting, and in a report simultaneously published online (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1409312]).
Counterbalancing this benefit was a statistically significant excess of moderately severe bleeding events among patients on longer-term DAPT, who had a 0.7% absolute increased rate, and a trend toward increased severe bleeds, with a 0.2% absolute increased rate. Patients on longer-term DAPT also showed an unexpected, 0.5% increased rate of both all cause death and noncardiovascular death. Detailed analysis indicated that this seemed to result from a “chance imbalance” in randomization that put an excess of patients with cancer into the 30-month DAPT subgroup, said Dr. Mauri, professor of medicine at Harvard Medical School and an interventional cardiologist at Brigham and Women’s Hospital, both in Boston.
DAPT treatment extending longer than 12 months switches the focus from preventing stent thrombosis to secondary prevention of all ischemic events, including those that occur elsewhere in a patient’s coronary arteries, noted Dr. Montalescot, who served as the meeting’s designated discussant for the DAPT trial and the other reported DAPT studies. This option, which can now be offered to appropriate patients, also raised the possibility of continuing DAPT indefinitely beyond 30 months in patients who continue to show no bleeding risk and can pay for ongoing treatment with a thienopyridine. But he advised waiting on the use of very prolonged DAPT until results arrive next year from the PEGASUS study.
ITALIC and ISAR-SAFE
Results from two other studies reported at the meeting looked at the other end of the spectrum, the safety of stopping DAPT after just 6 months. One of these, the ITALIC study, randomized 1,850 patients to 6 months or 24 months of treatment with aspirin and clopidogrel, and exclusively enrolled patients who received the Xience V everolimus-eluting, third-generation coronary stent. The results showed low and nearly identical 1.5% and 1.6% rates of the combined endpoint of major adverse events, including bleeds, in the two comparator arms after 24 months of follow-up. The results also appeared in an article published simultaneously online (J. Am. Coll. Card. 2014 [doi:10.1016/j.jacc.2014.11.008]).
A similarly designed study, ISAR-SAFE, randomized 4,005 PCI patients who received a DES to DAPT with aspirin and clopidogrel for either 6 or 12 months, and also showed a similar and low, roughly 1.5% rate of combined major adverse cardiovascular events and bleeds in both treatment arms, reported Dr. Stefanie Schulz-Schüpke, an interventional cardiologist at the German Heart Center in Munich.
These two studies, along with five prior reports that collectively randomized nearly 16,000 patients to 6 months of DAPT or a longer duration show a statistically significant reduction in major bleeds with good protection against ischemic events when DAPT stopped after 6 months, said Dr. Montalescot. “We can accept that 6 months is safer than 12 months of DAPT,” and it makes sense to stop after 6 months in a patient with a bleeding risk, but not in a patient with a high ischemia risk such as those with left main coronary disease, a history of stent thrombosis or myocardial infarction, a patient who received a first-generation DES, patients with extensive coronary disease or coronary stenting.*
While Dr. Montalescot, Dr. Antman, and others who heard these results agreed that they all pointed to the need for individualized decisions on DAPT duration, they also said the new findings were unlikely to change current guidelines. Existing PCI guidelines from the American Heart Association and American College of Cardiology call for a standard 12 months of DAPT in DES recipients, but offer clinicians to reduce or extend the duration when judged appropriate (J. Am. Coll. Cardiol. 2011;58:e44-e122). Guidelines from the European College of Cardiology call for 6 months of DAPT as standard, but also suggest that clinicians can reduce or lengthen the duration when appropriate (Eur. Heart J. 2014 [doi.org/10.1093/eurheartj/ehu278]).
According to three staffers from the FDA who also spoke at the session, the agency is also unlikely to change its guidance on DAPT in the immediate future, even though it triggered launch of the DAPT trial.
The DAPT trial “is large enough to allow us to answer some really critical public-health questions, and to potentially expand the indications for drug-eluting coronary stents,” said Dr. Bram D. Zuckerman, director of the division of cardiovascular devices of the FDA. But he and his colleagues who spoke during the session said that the agency will not update its recommendations or labels until the FDA staff has had a chance to study in detail the full data set collected in the DAPT trial. Concurrent with Dr. Mauri’s report, the agency issued a statement calling on physicians to continue to prescribe DAPT as they have in the past and for patients to continue to take all their prescribed medications.
Many physicians have already concluded that 6 months of DAPT is a practical way to enhance patient compliance with their regimen and minimize the money they spend on these medications, commented Dr. Richard C. Becker, professor of medicine and director of the Cardiovascular Institute at the University of Cincinnati. The three trials reported at the meeting “do not answer the question [of whether 6 months is adequate] because in each trial patients had already tolerated a period of DAPT before entering the study” Dr. Becker said in an interview.
The question of DAPT duration “is a question that clinicians will need to have with each of their patients, especially those who are tolerating DAPT,” commented Dr. Richard A. Chazal, an interventionalist and medical director of the Heart and Vascular Institute at the Lee Memorial Health System in Fort Myers, Fla.
Dr. Montalescot has been a consultant to more than a dozen pharmaceutical and device companies, including companies that market antiplatelet drugs. Dr. Antman has received grant support from Daiichi Sankyo. Dr. Mauri received personal fees from Medtronic, Recur, St. Jude, and Biotronik, and grant support from nine device manufacturer and drug companies. Dr. Schulz-Schüpke, Dr. Zuckerman, Dr. Becker, and Dr. Chazal had no relevant disclosures.
On Twitter@mitchelzoler
*CORRECTION, 11/18/2014: An earlier version of this article misstated the treatment length in patients with a high ischemia risk.
CHICAGO – Clinicians managing patients who have just received drug-eluting coronary stents need to individualize the duration of the antiplatelet therapy they prescribe and stop thinking that a single length of treatment works best for all patients, based on results from a trio of newly reported trials, as well as earlier study findings.
In general, the new findings seemed to show that following percutaneous coronary intervention (PCI) with a stent, patients with a low risk for stent thrombosis, myocardial infarction, or another type of ischemic event, as well as those with a high bleeding risk, fare best when their duration of dual antiplatelet therapy (DAPT) with aspirin plus a thienopyridine ends after 6 months, while patients with a low bleeding risk and a high risk for an ischemic event will usually do better when their DAPT continues well beyond 12 months, for 30 months and possibly longer.
“We now have results from 35,000 patients in randomized trials that addressed the question of duration of DAPT. We need to make up our minds, and it’s probably an individualized decision,” Dr. Gilles Montalescot said at the American Heart Association Scientific Sessions.
“The patients [in the three newly reported studies] were generally doing well, and so we are operating at the edge of competing risks” they face for ischemia and bleeding. “We need individualization of treatment, but what remains to be determined is, how do we make that decision? Who is more at risk for ischemic events and less at risk for bleeding, and who is more at risk for bleeding and less from ischemia?” commented Dr. Elliott M. Antman, professor of medicine and associate dean for clinical and translational research at Harvard University in Boston.
The DAPT trial
Drug-eluting stent recipients at increased risk for bleeding who are good candidates for a briefer, 6-month duration of DAPT include those with a history of a prior bleed, advanced age, pending need for surgery, patients who need anticoagulation treatment such as those with atrial fibrillation, patients with one or more comorbidities that put them at higher bleeding risk such as gastrointestinal disease or a history of stroke, and patients with a “nuisance” bleed, said Dr. Montalescot, a professor of cardiology at the University of Paris and director of the cardiac care unit at Pitié-Salpêtrière Hospital in Paris.
These conclusions emerged from a surge of new data from three studies presented at the meeting that all addressed DAPT duration following PCI.
Perhaps most noteworthy and anticipated were results from the Dual Antiplatelet Therapy study, a randomized trial that had its beginnings in 2006 when cardiologists first became alarmed by the potential risk from stent thrombosis associated with the use of first-generation DES, specifically the original sirolimus-eluting (Cypher) and paclitaxel-eluting (Taxus) models. At the urging of staffers at the Food and Drug Administration, a group of eight stent manufacturing companies and pharmaceutical companies joined together to sponsor the DAPT study, which started with nearly 23,000 patients who received a DES and, after their first year of DAPT treatment, whittled down to 9,961 patients who were eligible for randomization to either stop DAPT after 1 year or continue on DAPT for an additional 18 months (30 months total time on DAPT).
The results showed that this highly selected group of patients – who went through their first year on DAPT with no bleeding event, no ischemic event, and who were willing to be randomized – those assigned to 30 months of DAPT had a 1% absolute and 71% relative reduction in stent thrombosis, compared with patients who stopped DAPT after 12 months, and a 1.6% absolute and 29% relative reduction in their rate of major cardiovascular or cerebrovascular events, statistically significant differences for the study’s two primary endpoints. The reduction in major events was driven mainly by a 2% absolute reduction in the rate of myocardial infarctions, reported Dr. Laura Mauri at the meeting, and in a report simultaneously published online (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1409312]).
Counterbalancing this benefit was a statistically significant excess of moderately severe bleeding events among patients on longer-term DAPT, who had a 0.7% absolute increased rate, and a trend toward increased severe bleeds, with a 0.2% absolute increased rate. Patients on longer-term DAPT also showed an unexpected, 0.5% increased rate of both all cause death and noncardiovascular death. Detailed analysis indicated that this seemed to result from a “chance imbalance” in randomization that put an excess of patients with cancer into the 30-month DAPT subgroup, said Dr. Mauri, professor of medicine at Harvard Medical School and an interventional cardiologist at Brigham and Women’s Hospital, both in Boston.
DAPT treatment extending longer than 12 months switches the focus from preventing stent thrombosis to secondary prevention of all ischemic events, including those that occur elsewhere in a patient’s coronary arteries, noted Dr. Montalescot, who served as the meeting’s designated discussant for the DAPT trial and the other reported DAPT studies. This option, which can now be offered to appropriate patients, also raised the possibility of continuing DAPT indefinitely beyond 30 months in patients who continue to show no bleeding risk and can pay for ongoing treatment with a thienopyridine. But he advised waiting on the use of very prolonged DAPT until results arrive next year from the PEGASUS study.
ITALIC and ISAR-SAFE
Results from two other studies reported at the meeting looked at the other end of the spectrum, the safety of stopping DAPT after just 6 months. One of these, the ITALIC study, randomized 1,850 patients to 6 months or 24 months of treatment with aspirin and clopidogrel, and exclusively enrolled patients who received the Xience V everolimus-eluting, third-generation coronary stent. The results showed low and nearly identical 1.5% and 1.6% rates of the combined endpoint of major adverse events, including bleeds, in the two comparator arms after 24 months of follow-up. The results also appeared in an article published simultaneously online (J. Am. Coll. Card. 2014 [doi:10.1016/j.jacc.2014.11.008]).
A similarly designed study, ISAR-SAFE, randomized 4,005 PCI patients who received a DES to DAPT with aspirin and clopidogrel for either 6 or 12 months, and also showed a similar and low, roughly 1.5% rate of combined major adverse cardiovascular events and bleeds in both treatment arms, reported Dr. Stefanie Schulz-Schüpke, an interventional cardiologist at the German Heart Center in Munich.
These two studies, along with five prior reports that collectively randomized nearly 16,000 patients to 6 months of DAPT or a longer duration show a statistically significant reduction in major bleeds with good protection against ischemic events when DAPT stopped after 6 months, said Dr. Montalescot. “We can accept that 6 months is safer than 12 months of DAPT,” and it makes sense to stop after 6 months in a patient with a bleeding risk, but not in a patient with a high ischemia risk such as those with left main coronary disease, a history of stent thrombosis or myocardial infarction, a patient who received a first-generation DES, patients with extensive coronary disease or coronary stenting.*
While Dr. Montalescot, Dr. Antman, and others who heard these results agreed that they all pointed to the need for individualized decisions on DAPT duration, they also said the new findings were unlikely to change current guidelines. Existing PCI guidelines from the American Heart Association and American College of Cardiology call for a standard 12 months of DAPT in DES recipients, but offer clinicians to reduce or extend the duration when judged appropriate (J. Am. Coll. Cardiol. 2011;58:e44-e122). Guidelines from the European College of Cardiology call for 6 months of DAPT as standard, but also suggest that clinicians can reduce or lengthen the duration when appropriate (Eur. Heart J. 2014 [doi.org/10.1093/eurheartj/ehu278]).
According to three staffers from the FDA who also spoke at the session, the agency is also unlikely to change its guidance on DAPT in the immediate future, even though it triggered launch of the DAPT trial.
The DAPT trial “is large enough to allow us to answer some really critical public-health questions, and to potentially expand the indications for drug-eluting coronary stents,” said Dr. Bram D. Zuckerman, director of the division of cardiovascular devices of the FDA. But he and his colleagues who spoke during the session said that the agency will not update its recommendations or labels until the FDA staff has had a chance to study in detail the full data set collected in the DAPT trial. Concurrent with Dr. Mauri’s report, the agency issued a statement calling on physicians to continue to prescribe DAPT as they have in the past and for patients to continue to take all their prescribed medications.
Many physicians have already concluded that 6 months of DAPT is a practical way to enhance patient compliance with their regimen and minimize the money they spend on these medications, commented Dr. Richard C. Becker, professor of medicine and director of the Cardiovascular Institute at the University of Cincinnati. The three trials reported at the meeting “do not answer the question [of whether 6 months is adequate] because in each trial patients had already tolerated a period of DAPT before entering the study” Dr. Becker said in an interview.
The question of DAPT duration “is a question that clinicians will need to have with each of their patients, especially those who are tolerating DAPT,” commented Dr. Richard A. Chazal, an interventionalist and medical director of the Heart and Vascular Institute at the Lee Memorial Health System in Fort Myers, Fla.
Dr. Montalescot has been a consultant to more than a dozen pharmaceutical and device companies, including companies that market antiplatelet drugs. Dr. Antman has received grant support from Daiichi Sankyo. Dr. Mauri received personal fees from Medtronic, Recur, St. Jude, and Biotronik, and grant support from nine device manufacturer and drug companies. Dr. Schulz-Schüpke, Dr. Zuckerman, Dr. Becker, and Dr. Chazal had no relevant disclosures.
On Twitter@mitchelzoler
*CORRECTION, 11/18/2014: An earlier version of this article misstated the treatment length in patients with a high ischemia risk.
CHICAGO – Clinicians managing patients who have just received drug-eluting coronary stents need to individualize the duration of the antiplatelet therapy they prescribe and stop thinking that a single length of treatment works best for all patients, based on results from a trio of newly reported trials, as well as earlier study findings.
In general, the new findings seemed to show that following percutaneous coronary intervention (PCI) with a stent, patients with a low risk for stent thrombosis, myocardial infarction, or another type of ischemic event, as well as those with a high bleeding risk, fare best when their duration of dual antiplatelet therapy (DAPT) with aspirin plus a thienopyridine ends after 6 months, while patients with a low bleeding risk and a high risk for an ischemic event will usually do better when their DAPT continues well beyond 12 months, for 30 months and possibly longer.
“We now have results from 35,000 patients in randomized trials that addressed the question of duration of DAPT. We need to make up our minds, and it’s probably an individualized decision,” Dr. Gilles Montalescot said at the American Heart Association Scientific Sessions.
“The patients [in the three newly reported studies] were generally doing well, and so we are operating at the edge of competing risks” they face for ischemia and bleeding. “We need individualization of treatment, but what remains to be determined is, how do we make that decision? Who is more at risk for ischemic events and less at risk for bleeding, and who is more at risk for bleeding and less from ischemia?” commented Dr. Elliott M. Antman, professor of medicine and associate dean for clinical and translational research at Harvard University in Boston.
The DAPT trial
Drug-eluting stent recipients at increased risk for bleeding who are good candidates for a briefer, 6-month duration of DAPT include those with a history of a prior bleed, advanced age, pending need for surgery, patients who need anticoagulation treatment such as those with atrial fibrillation, patients with one or more comorbidities that put them at higher bleeding risk such as gastrointestinal disease or a history of stroke, and patients with a “nuisance” bleed, said Dr. Montalescot, a professor of cardiology at the University of Paris and director of the cardiac care unit at Pitié-Salpêtrière Hospital in Paris.
These conclusions emerged from a surge of new data from three studies presented at the meeting that all addressed DAPT duration following PCI.
Perhaps most noteworthy and anticipated were results from the Dual Antiplatelet Therapy study, a randomized trial that had its beginnings in 2006 when cardiologists first became alarmed by the potential risk from stent thrombosis associated with the use of first-generation DES, specifically the original sirolimus-eluting (Cypher) and paclitaxel-eluting (Taxus) models. At the urging of staffers at the Food and Drug Administration, a group of eight stent manufacturing companies and pharmaceutical companies joined together to sponsor the DAPT study, which started with nearly 23,000 patients who received a DES and, after their first year of DAPT treatment, whittled down to 9,961 patients who were eligible for randomization to either stop DAPT after 1 year or continue on DAPT for an additional 18 months (30 months total time on DAPT).
The results showed that this highly selected group of patients – who went through their first year on DAPT with no bleeding event, no ischemic event, and who were willing to be randomized – those assigned to 30 months of DAPT had a 1% absolute and 71% relative reduction in stent thrombosis, compared with patients who stopped DAPT after 12 months, and a 1.6% absolute and 29% relative reduction in their rate of major cardiovascular or cerebrovascular events, statistically significant differences for the study’s two primary endpoints. The reduction in major events was driven mainly by a 2% absolute reduction in the rate of myocardial infarctions, reported Dr. Laura Mauri at the meeting, and in a report simultaneously published online (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1409312]).
Counterbalancing this benefit was a statistically significant excess of moderately severe bleeding events among patients on longer-term DAPT, who had a 0.7% absolute increased rate, and a trend toward increased severe bleeds, with a 0.2% absolute increased rate. Patients on longer-term DAPT also showed an unexpected, 0.5% increased rate of both all cause death and noncardiovascular death. Detailed analysis indicated that this seemed to result from a “chance imbalance” in randomization that put an excess of patients with cancer into the 30-month DAPT subgroup, said Dr. Mauri, professor of medicine at Harvard Medical School and an interventional cardiologist at Brigham and Women’s Hospital, both in Boston.
DAPT treatment extending longer than 12 months switches the focus from preventing stent thrombosis to secondary prevention of all ischemic events, including those that occur elsewhere in a patient’s coronary arteries, noted Dr. Montalescot, who served as the meeting’s designated discussant for the DAPT trial and the other reported DAPT studies. This option, which can now be offered to appropriate patients, also raised the possibility of continuing DAPT indefinitely beyond 30 months in patients who continue to show no bleeding risk and can pay for ongoing treatment with a thienopyridine. But he advised waiting on the use of very prolonged DAPT until results arrive next year from the PEGASUS study.
ITALIC and ISAR-SAFE
Results from two other studies reported at the meeting looked at the other end of the spectrum, the safety of stopping DAPT after just 6 months. One of these, the ITALIC study, randomized 1,850 patients to 6 months or 24 months of treatment with aspirin and clopidogrel, and exclusively enrolled patients who received the Xience V everolimus-eluting, third-generation coronary stent. The results showed low and nearly identical 1.5% and 1.6% rates of the combined endpoint of major adverse events, including bleeds, in the two comparator arms after 24 months of follow-up. The results also appeared in an article published simultaneously online (J. Am. Coll. Card. 2014 [doi:10.1016/j.jacc.2014.11.008]).
A similarly designed study, ISAR-SAFE, randomized 4,005 PCI patients who received a DES to DAPT with aspirin and clopidogrel for either 6 or 12 months, and also showed a similar and low, roughly 1.5% rate of combined major adverse cardiovascular events and bleeds in both treatment arms, reported Dr. Stefanie Schulz-Schüpke, an interventional cardiologist at the German Heart Center in Munich.
These two studies, along with five prior reports that collectively randomized nearly 16,000 patients to 6 months of DAPT or a longer duration show a statistically significant reduction in major bleeds with good protection against ischemic events when DAPT stopped after 6 months, said Dr. Montalescot. “We can accept that 6 months is safer than 12 months of DAPT,” and it makes sense to stop after 6 months in a patient with a bleeding risk, but not in a patient with a high ischemia risk such as those with left main coronary disease, a history of stent thrombosis or myocardial infarction, a patient who received a first-generation DES, patients with extensive coronary disease or coronary stenting.*
While Dr. Montalescot, Dr. Antman, and others who heard these results agreed that they all pointed to the need for individualized decisions on DAPT duration, they also said the new findings were unlikely to change current guidelines. Existing PCI guidelines from the American Heart Association and American College of Cardiology call for a standard 12 months of DAPT in DES recipients, but offer clinicians to reduce or extend the duration when judged appropriate (J. Am. Coll. Cardiol. 2011;58:e44-e122). Guidelines from the European College of Cardiology call for 6 months of DAPT as standard, but also suggest that clinicians can reduce or lengthen the duration when appropriate (Eur. Heart J. 2014 [doi.org/10.1093/eurheartj/ehu278]).
According to three staffers from the FDA who also spoke at the session, the agency is also unlikely to change its guidance on DAPT in the immediate future, even though it triggered launch of the DAPT trial.
The DAPT trial “is large enough to allow us to answer some really critical public-health questions, and to potentially expand the indications for drug-eluting coronary stents,” said Dr. Bram D. Zuckerman, director of the division of cardiovascular devices of the FDA. But he and his colleagues who spoke during the session said that the agency will not update its recommendations or labels until the FDA staff has had a chance to study in detail the full data set collected in the DAPT trial. Concurrent with Dr. Mauri’s report, the agency issued a statement calling on physicians to continue to prescribe DAPT as they have in the past and for patients to continue to take all their prescribed medications.
Many physicians have already concluded that 6 months of DAPT is a practical way to enhance patient compliance with their regimen and minimize the money they spend on these medications, commented Dr. Richard C. Becker, professor of medicine and director of the Cardiovascular Institute at the University of Cincinnati. The three trials reported at the meeting “do not answer the question [of whether 6 months is adequate] because in each trial patients had already tolerated a period of DAPT before entering the study” Dr. Becker said in an interview.
The question of DAPT duration “is a question that clinicians will need to have with each of their patients, especially those who are tolerating DAPT,” commented Dr. Richard A. Chazal, an interventionalist and medical director of the Heart and Vascular Institute at the Lee Memorial Health System in Fort Myers, Fla.
Dr. Montalescot has been a consultant to more than a dozen pharmaceutical and device companies, including companies that market antiplatelet drugs. Dr. Antman has received grant support from Daiichi Sankyo. Dr. Mauri received personal fees from Medtronic, Recur, St. Jude, and Biotronik, and grant support from nine device manufacturer and drug companies. Dr. Schulz-Schüpke, Dr. Zuckerman, Dr. Becker, and Dr. Chazal had no relevant disclosures.
On Twitter@mitchelzoler
*CORRECTION, 11/18/2014: An earlier version of this article misstated the treatment length in patients with a high ischemia risk.
EXPERT OPINION FROM THE AHA SCIENTIFIC SESSIONS
Ebola entrenched in West Africa, recurrence inevitable
VIENNA – The world had better get used to dealing with Ebola virus outbreaks, because even if the west African outbreak comes under control others will inevitably follow until an effective vaccine becomes widely used.
On top of that, experts who gathered at the International Meeting on Emerging Disease and Surveillance said that they saw no quick end to the current west African outbreak.
“At this point, Ebola is so entrenched in west Africa that it will come back again. It is basically part of the [west African] ecology,” Dr. Adriano G. Duse said in an interview. He also painted a pessimistic picture of short-term prospects for controlling the current outbreak.
“It will be around [in west Africa] for at least the next year. There is no sign of it abating,” said Dr. Duse, professor and head of the department of clinical microbiology and infectious diseases at the University of Witwatersrand in Johannesburg, South Africa, and a specialist in viral hemorrhagic fevers. “We suspect that the [Ebola] virus has been around in west Africa for a long time, and it was just a matter of time until it went into people.” He noted that the Ebola species currently circulating in west Africa closely matches the Zaire strain that was the type that first surfaced in people in 1976.
“We are now so high in numbers in west Africa that it will take months” to control the current outbreak, agreed Dr. Hilde de Clerck, a family physician who serves as a mobile implementation officer for viral hemorrhagic fevers for Médicins Sans Frontières (MSF; Doctors Without Borders), who began working last March in Guinea on patient care and infection control. “At MSF, we are planning that it will take at least 6-12 months, but that is a guess; we have no clue” how long the current outbreak will continue, Dr. de Clerck said in an interview. “At this time, we are running behind.”
On Nov. 14, the World Health Organization (WHO) pegged the number of Ebola virus infections known to have occurred in Guinea, Sierra Leone, and Liberia as of Nov. 11 at 14,383 (with a total of 14,413 total infection worldwide since the outbreak began), with 5,165 Ebola fatalities in west Africa and 5,177 worldwide. Dr. de Clerck, Dr. Duse, and others said that they believe that the WHO’s numbers greatly underestimate the true scope of the outbreak, even though the official numbers dwarf the size of all prior Ebola virus outbreaks since the virus first emerged in 1976; previous outbreaks always involved fewer than 1,000 infected people.
“The numbers we have seen show that the WHO’s numbers can’t be right,” Dr. de Clerck said.
Factors fueling Ebola’s spread
Dr. de Clerck attributed the unprecedented spread of Ebola during this outbreak to the high mobility of the people who live in the region where Guinea, Sierra Leone, and Liberia share borders. She described people in the region who routinely travel as much as several hundred kilometers from one day to the next, and the easy flow of traffic from one country to another. She also cited as a major factor in the virus’s spread the large funerals traditionally held by the people in the region that typically involve contact with the body of the deceased.
But perhaps most important in the outbreak’s spread was a slow initial response to the first cases in the region. Dr. Duse criticized the governments of the three affected countries for their lax response to the onset of the outbreak, while he also praised Nigeria for taking a dramatically different tack.
The initial response to Ebola in Guinea and its neighboring countries was “denial” and “apathy,” and the responses also “lacked funding,” Dr. Duse said at the meeting. “It would have come to an end much sooner if the response had been mobilized quicker.” In contrast, the Nigerian response “was exceptionally swift,” and serves as a “role model for how to approach” future Ebola outbreaks.
Oyewale Tomori, D.V.M., Ph.D., president of the Nigerian Academy of Science, called the approach of many African countries to Ebola as “an ocean of apathy, denial, and unpreparedness.” In Nigeria, an Ebola management center opened 3 days after an Ebola-infected person arrived at Lagos airport from Liberia on July 20. That one case led to the infection of 20 other people, but the chain of infection stopped there, helped no doubt by a physician strike at the time which meant the index case went to a private hospital instead of a public hospital.
“We were lucky,” said Dr. Tomori. “We would have had a much bigger problem if the patient had gone to a teaching hospital.”
On Oct. 20, the WHO declared Nigeria Ebola free.
Ebola also spread this year in the Democratic Republic of Congo (DRC) starting in August, an outbreak documented as unrelated to the one in west Africa and resulting from a DRC resident eating Ebola-carrying bushmeat. In the DRC, a quick and thorough response contained the spread and appears to have brought the outbreak to an end. On Nov. 15, the DRC’s minister of health said that the outbreak was over.
The experience this year in both Nigeria and the DRC shows that “Ebola is completely preventable if you educate people on how to avoid it,” said William Karesh, D.V.M., executive vice president for health and policy at the EcoHealth Alliance in New York.
Prospects for the west African outbreak
Given Ebola’s spread now in west Africa, “it is incredibly daunting to isolate all the cases,” said Dr. Lawrence C. Madoff, a professor of medicine at the University of Massachusetts in Worcester and director of epidemiology and immunization at the Massachusetts Department of Public Health in Boston. “The infrastructure [in the affected west African countries] is missing, challenged, or stretched way too thin, and it’s been incredibly difficult,” but he added that eventually he expects the epidemic curve of Ebola to peak and fall.
“As a rule, outbreaks end, and I don’t see any reason why this outbreak won’t also end. Sometimes, like in the great plagues of the Middle Ages, they can go on for a long time and involve many people, but eventually they do end.”
Dr. Duse agreed, and cited Ebola’s high mortality rate as a factor that limits the duration of outbreaks. “There has never been an Ebola outbreak that was sustained,” he noted.
“Humans are not Ebola carriers; they either die or recover, and stop shedding virus and are immune,” noted Dr. Karesh. But even when the current outbreak in west Africa ends, the threat remains of new introductions of Ebola into people from the reservoirs of virus that exist in bats and primates. “By the time the west African outbreak is controlled, there could be other spillover events” from animals to people, he cautioned.
Dr. Duse, Dr. de Clerck, Dr. Tomori, Dr. Karesh, and Dr. Madoff had no disclosures.
On Twitter @mitchelzoler
VIENNA – The world had better get used to dealing with Ebola virus outbreaks, because even if the west African outbreak comes under control others will inevitably follow until an effective vaccine becomes widely used.
On top of that, experts who gathered at the International Meeting on Emerging Disease and Surveillance said that they saw no quick end to the current west African outbreak.
“At this point, Ebola is so entrenched in west Africa that it will come back again. It is basically part of the [west African] ecology,” Dr. Adriano G. Duse said in an interview. He also painted a pessimistic picture of short-term prospects for controlling the current outbreak.
“It will be around [in west Africa] for at least the next year. There is no sign of it abating,” said Dr. Duse, professor and head of the department of clinical microbiology and infectious diseases at the University of Witwatersrand in Johannesburg, South Africa, and a specialist in viral hemorrhagic fevers. “We suspect that the [Ebola] virus has been around in west Africa for a long time, and it was just a matter of time until it went into people.” He noted that the Ebola species currently circulating in west Africa closely matches the Zaire strain that was the type that first surfaced in people in 1976.
“We are now so high in numbers in west Africa that it will take months” to control the current outbreak, agreed Dr. Hilde de Clerck, a family physician who serves as a mobile implementation officer for viral hemorrhagic fevers for Médicins Sans Frontières (MSF; Doctors Without Borders), who began working last March in Guinea on patient care and infection control. “At MSF, we are planning that it will take at least 6-12 months, but that is a guess; we have no clue” how long the current outbreak will continue, Dr. de Clerck said in an interview. “At this time, we are running behind.”
On Nov. 14, the World Health Organization (WHO) pegged the number of Ebola virus infections known to have occurred in Guinea, Sierra Leone, and Liberia as of Nov. 11 at 14,383 (with a total of 14,413 total infection worldwide since the outbreak began), with 5,165 Ebola fatalities in west Africa and 5,177 worldwide. Dr. de Clerck, Dr. Duse, and others said that they believe that the WHO’s numbers greatly underestimate the true scope of the outbreak, even though the official numbers dwarf the size of all prior Ebola virus outbreaks since the virus first emerged in 1976; previous outbreaks always involved fewer than 1,000 infected people.
“The numbers we have seen show that the WHO’s numbers can’t be right,” Dr. de Clerck said.
Factors fueling Ebola’s spread
Dr. de Clerck attributed the unprecedented spread of Ebola during this outbreak to the high mobility of the people who live in the region where Guinea, Sierra Leone, and Liberia share borders. She described people in the region who routinely travel as much as several hundred kilometers from one day to the next, and the easy flow of traffic from one country to another. She also cited as a major factor in the virus’s spread the large funerals traditionally held by the people in the region that typically involve contact with the body of the deceased.
But perhaps most important in the outbreak’s spread was a slow initial response to the first cases in the region. Dr. Duse criticized the governments of the three affected countries for their lax response to the onset of the outbreak, while he also praised Nigeria for taking a dramatically different tack.
The initial response to Ebola in Guinea and its neighboring countries was “denial” and “apathy,” and the responses also “lacked funding,” Dr. Duse said at the meeting. “It would have come to an end much sooner if the response had been mobilized quicker.” In contrast, the Nigerian response “was exceptionally swift,” and serves as a “role model for how to approach” future Ebola outbreaks.
Oyewale Tomori, D.V.M., Ph.D., president of the Nigerian Academy of Science, called the approach of many African countries to Ebola as “an ocean of apathy, denial, and unpreparedness.” In Nigeria, an Ebola management center opened 3 days after an Ebola-infected person arrived at Lagos airport from Liberia on July 20. That one case led to the infection of 20 other people, but the chain of infection stopped there, helped no doubt by a physician strike at the time which meant the index case went to a private hospital instead of a public hospital.
“We were lucky,” said Dr. Tomori. “We would have had a much bigger problem if the patient had gone to a teaching hospital.”
On Oct. 20, the WHO declared Nigeria Ebola free.
Ebola also spread this year in the Democratic Republic of Congo (DRC) starting in August, an outbreak documented as unrelated to the one in west Africa and resulting from a DRC resident eating Ebola-carrying bushmeat. In the DRC, a quick and thorough response contained the spread and appears to have brought the outbreak to an end. On Nov. 15, the DRC’s minister of health said that the outbreak was over.
The experience this year in both Nigeria and the DRC shows that “Ebola is completely preventable if you educate people on how to avoid it,” said William Karesh, D.V.M., executive vice president for health and policy at the EcoHealth Alliance in New York.
Prospects for the west African outbreak
Given Ebola’s spread now in west Africa, “it is incredibly daunting to isolate all the cases,” said Dr. Lawrence C. Madoff, a professor of medicine at the University of Massachusetts in Worcester and director of epidemiology and immunization at the Massachusetts Department of Public Health in Boston. “The infrastructure [in the affected west African countries] is missing, challenged, or stretched way too thin, and it’s been incredibly difficult,” but he added that eventually he expects the epidemic curve of Ebola to peak and fall.
“As a rule, outbreaks end, and I don’t see any reason why this outbreak won’t also end. Sometimes, like in the great plagues of the Middle Ages, they can go on for a long time and involve many people, but eventually they do end.”
Dr. Duse agreed, and cited Ebola’s high mortality rate as a factor that limits the duration of outbreaks. “There has never been an Ebola outbreak that was sustained,” he noted.
“Humans are not Ebola carriers; they either die or recover, and stop shedding virus and are immune,” noted Dr. Karesh. But even when the current outbreak in west Africa ends, the threat remains of new introductions of Ebola into people from the reservoirs of virus that exist in bats and primates. “By the time the west African outbreak is controlled, there could be other spillover events” from animals to people, he cautioned.
Dr. Duse, Dr. de Clerck, Dr. Tomori, Dr. Karesh, and Dr. Madoff had no disclosures.
On Twitter @mitchelzoler
VIENNA – The world had better get used to dealing with Ebola virus outbreaks, because even if the west African outbreak comes under control others will inevitably follow until an effective vaccine becomes widely used.
On top of that, experts who gathered at the International Meeting on Emerging Disease and Surveillance said that they saw no quick end to the current west African outbreak.
“At this point, Ebola is so entrenched in west Africa that it will come back again. It is basically part of the [west African] ecology,” Dr. Adriano G. Duse said in an interview. He also painted a pessimistic picture of short-term prospects for controlling the current outbreak.
“It will be around [in west Africa] for at least the next year. There is no sign of it abating,” said Dr. Duse, professor and head of the department of clinical microbiology and infectious diseases at the University of Witwatersrand in Johannesburg, South Africa, and a specialist in viral hemorrhagic fevers. “We suspect that the [Ebola] virus has been around in west Africa for a long time, and it was just a matter of time until it went into people.” He noted that the Ebola species currently circulating in west Africa closely matches the Zaire strain that was the type that first surfaced in people in 1976.
“We are now so high in numbers in west Africa that it will take months” to control the current outbreak, agreed Dr. Hilde de Clerck, a family physician who serves as a mobile implementation officer for viral hemorrhagic fevers for Médicins Sans Frontières (MSF; Doctors Without Borders), who began working last March in Guinea on patient care and infection control. “At MSF, we are planning that it will take at least 6-12 months, but that is a guess; we have no clue” how long the current outbreak will continue, Dr. de Clerck said in an interview. “At this time, we are running behind.”
On Nov. 14, the World Health Organization (WHO) pegged the number of Ebola virus infections known to have occurred in Guinea, Sierra Leone, and Liberia as of Nov. 11 at 14,383 (with a total of 14,413 total infection worldwide since the outbreak began), with 5,165 Ebola fatalities in west Africa and 5,177 worldwide. Dr. de Clerck, Dr. Duse, and others said that they believe that the WHO’s numbers greatly underestimate the true scope of the outbreak, even though the official numbers dwarf the size of all prior Ebola virus outbreaks since the virus first emerged in 1976; previous outbreaks always involved fewer than 1,000 infected people.
“The numbers we have seen show that the WHO’s numbers can’t be right,” Dr. de Clerck said.
Factors fueling Ebola’s spread
Dr. de Clerck attributed the unprecedented spread of Ebola during this outbreak to the high mobility of the people who live in the region where Guinea, Sierra Leone, and Liberia share borders. She described people in the region who routinely travel as much as several hundred kilometers from one day to the next, and the easy flow of traffic from one country to another. She also cited as a major factor in the virus’s spread the large funerals traditionally held by the people in the region that typically involve contact with the body of the deceased.
But perhaps most important in the outbreak’s spread was a slow initial response to the first cases in the region. Dr. Duse criticized the governments of the three affected countries for their lax response to the onset of the outbreak, while he also praised Nigeria for taking a dramatically different tack.
The initial response to Ebola in Guinea and its neighboring countries was “denial” and “apathy,” and the responses also “lacked funding,” Dr. Duse said at the meeting. “It would have come to an end much sooner if the response had been mobilized quicker.” In contrast, the Nigerian response “was exceptionally swift,” and serves as a “role model for how to approach” future Ebola outbreaks.
Oyewale Tomori, D.V.M., Ph.D., president of the Nigerian Academy of Science, called the approach of many African countries to Ebola as “an ocean of apathy, denial, and unpreparedness.” In Nigeria, an Ebola management center opened 3 days after an Ebola-infected person arrived at Lagos airport from Liberia on July 20. That one case led to the infection of 20 other people, but the chain of infection stopped there, helped no doubt by a physician strike at the time which meant the index case went to a private hospital instead of a public hospital.
“We were lucky,” said Dr. Tomori. “We would have had a much bigger problem if the patient had gone to a teaching hospital.”
On Oct. 20, the WHO declared Nigeria Ebola free.
Ebola also spread this year in the Democratic Republic of Congo (DRC) starting in August, an outbreak documented as unrelated to the one in west Africa and resulting from a DRC resident eating Ebola-carrying bushmeat. In the DRC, a quick and thorough response contained the spread and appears to have brought the outbreak to an end. On Nov. 15, the DRC’s minister of health said that the outbreak was over.
The experience this year in both Nigeria and the DRC shows that “Ebola is completely preventable if you educate people on how to avoid it,” said William Karesh, D.V.M., executive vice president for health and policy at the EcoHealth Alliance in New York.
Prospects for the west African outbreak
Given Ebola’s spread now in west Africa, “it is incredibly daunting to isolate all the cases,” said Dr. Lawrence C. Madoff, a professor of medicine at the University of Massachusetts in Worcester and director of epidemiology and immunization at the Massachusetts Department of Public Health in Boston. “The infrastructure [in the affected west African countries] is missing, challenged, or stretched way too thin, and it’s been incredibly difficult,” but he added that eventually he expects the epidemic curve of Ebola to peak and fall.
“As a rule, outbreaks end, and I don’t see any reason why this outbreak won’t also end. Sometimes, like in the great plagues of the Middle Ages, they can go on for a long time and involve many people, but eventually they do end.”
Dr. Duse agreed, and cited Ebola’s high mortality rate as a factor that limits the duration of outbreaks. “There has never been an Ebola outbreak that was sustained,” he noted.
“Humans are not Ebola carriers; they either die or recover, and stop shedding virus and are immune,” noted Dr. Karesh. But even when the current outbreak in west Africa ends, the threat remains of new introductions of Ebola into people from the reservoirs of virus that exist in bats and primates. “By the time the west African outbreak is controlled, there could be other spillover events” from animals to people, he cautioned.
Dr. Duse, Dr. de Clerck, Dr. Tomori, Dr. Karesh, and Dr. Madoff had no disclosures.
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM IMED 2014
VIDEO: DAPT trials send mixed messages on treatment duration
CHICAGO – The four studies reported during the American Heart Association Scientific Sessions that looked at the safety and efficacy of different durations of dual antiplatelet therapy following coronary stenting addressed two different issues.
Two of the studies, ISAR-SAFE and ITALIC, both based in Europe, addressed the question of whether 6 months of dual antiplatelet therapy (DAPT) was as safe and effective as either 12 or 24 months of treatment, and the results from both studies indicated that a 6-month duration is as effective as longer term treatment. This means that especially for patients with an increased bleeding risk or another good reason to stop DAPT in the short term, such as patients who need surgery or those with atrial fibrillation who need treatment with an oral anticoagulant, stopping DAPT after 6 months is a reasonable and safe approach, Dr. Gilles Montalescot said during an interview at the meeting. More than half the patients who undergo coronary artery stenting likely fall into this subgroup, and perhaps as many as 60% or 70% of patients, estimated Dr. Montalescot, a professor of cardiology at the University of Paris and director of the cardiac care unit at Pitié-Salpêtrière Hospital in Paris.
But results from the other two DAPT trials reported at the meeting, TAXUS Liberté and DAPT, showed that for the subgroup of patients who can reasonably continue on DAPT beyond 6 months continuing the treatment out to 30 months led to substantially fewer ischemic events compared with patients who came off DAPT after 12 months, with a modest increase in bleeding events. Hence, for patients with a reduced risk for bleeding, more prolonged DAPT treatment, for as long as 30 months, produced a net benefit.
Many of the ischemic events prevented by more prolonged DAPT occurred in coronary sites outside of the placed stents, suggesting that this benefit is due more to secondary coronary disease prevention rather than prevention of late stent thrombosis, noted Dr. Montalescot. This raises the question of whether DAPT should continue indefinitely in coronary disease patients with a low bleeding risk. The current trial results do not fully resolve this, but if results from another study, PEGASUS, expected next March show similar findings, the accumulated data may support very long-term DAPT treatment in selected patients with coronary artery disease.
Dr. Montalescot said that he has been a consultant to more than a dozen pharmaceutical and device companies, including companies that market antiplatelet drugs.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
CHICAGO – The four studies reported during the American Heart Association Scientific Sessions that looked at the safety and efficacy of different durations of dual antiplatelet therapy following coronary stenting addressed two different issues.
Two of the studies, ISAR-SAFE and ITALIC, both based in Europe, addressed the question of whether 6 months of dual antiplatelet therapy (DAPT) was as safe and effective as either 12 or 24 months of treatment, and the results from both studies indicated that a 6-month duration is as effective as longer term treatment. This means that especially for patients with an increased bleeding risk or another good reason to stop DAPT in the short term, such as patients who need surgery or those with atrial fibrillation who need treatment with an oral anticoagulant, stopping DAPT after 6 months is a reasonable and safe approach, Dr. Gilles Montalescot said during an interview at the meeting. More than half the patients who undergo coronary artery stenting likely fall into this subgroup, and perhaps as many as 60% or 70% of patients, estimated Dr. Montalescot, a professor of cardiology at the University of Paris and director of the cardiac care unit at Pitié-Salpêtrière Hospital in Paris.
But results from the other two DAPT trials reported at the meeting, TAXUS Liberté and DAPT, showed that for the subgroup of patients who can reasonably continue on DAPT beyond 6 months continuing the treatment out to 30 months led to substantially fewer ischemic events compared with patients who came off DAPT after 12 months, with a modest increase in bleeding events. Hence, for patients with a reduced risk for bleeding, more prolonged DAPT treatment, for as long as 30 months, produced a net benefit.
Many of the ischemic events prevented by more prolonged DAPT occurred in coronary sites outside of the placed stents, suggesting that this benefit is due more to secondary coronary disease prevention rather than prevention of late stent thrombosis, noted Dr. Montalescot. This raises the question of whether DAPT should continue indefinitely in coronary disease patients with a low bleeding risk. The current trial results do not fully resolve this, but if results from another study, PEGASUS, expected next March show similar findings, the accumulated data may support very long-term DAPT treatment in selected patients with coronary artery disease.
Dr. Montalescot said that he has been a consultant to more than a dozen pharmaceutical and device companies, including companies that market antiplatelet drugs.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
CHICAGO – The four studies reported during the American Heart Association Scientific Sessions that looked at the safety and efficacy of different durations of dual antiplatelet therapy following coronary stenting addressed two different issues.
Two of the studies, ISAR-SAFE and ITALIC, both based in Europe, addressed the question of whether 6 months of dual antiplatelet therapy (DAPT) was as safe and effective as either 12 or 24 months of treatment, and the results from both studies indicated that a 6-month duration is as effective as longer term treatment. This means that especially for patients with an increased bleeding risk or another good reason to stop DAPT in the short term, such as patients who need surgery or those with atrial fibrillation who need treatment with an oral anticoagulant, stopping DAPT after 6 months is a reasonable and safe approach, Dr. Gilles Montalescot said during an interview at the meeting. More than half the patients who undergo coronary artery stenting likely fall into this subgroup, and perhaps as many as 60% or 70% of patients, estimated Dr. Montalescot, a professor of cardiology at the University of Paris and director of the cardiac care unit at Pitié-Salpêtrière Hospital in Paris.
But results from the other two DAPT trials reported at the meeting, TAXUS Liberté and DAPT, showed that for the subgroup of patients who can reasonably continue on DAPT beyond 6 months continuing the treatment out to 30 months led to substantially fewer ischemic events compared with patients who came off DAPT after 12 months, with a modest increase in bleeding events. Hence, for patients with a reduced risk for bleeding, more prolonged DAPT treatment, for as long as 30 months, produced a net benefit.
Many of the ischemic events prevented by more prolonged DAPT occurred in coronary sites outside of the placed stents, suggesting that this benefit is due more to secondary coronary disease prevention rather than prevention of late stent thrombosis, noted Dr. Montalescot. This raises the question of whether DAPT should continue indefinitely in coronary disease patients with a low bleeding risk. The current trial results do not fully resolve this, but if results from another study, PEGASUS, expected next March show similar findings, the accumulated data may support very long-term DAPT treatment in selected patients with coronary artery disease.
Dr. Montalescot said that he has been a consultant to more than a dozen pharmaceutical and device companies, including companies that market antiplatelet drugs.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM AHA 2014
VIDEO: West African Ebola scope makes control uncertain
VIENNA – The huge scope of the West African Ebola outbreak makes bringing it under control an unprecedented challenge with an uncertain outcome, Dr. Hilde de Clerck said in an interview during the International Meeting on Emerging Diseases and Surveillance.
The large number of people who have been infected with Ebola in the West African countries of Guinea, Sierra Leone, and Liberia – close to 14,000 identified cases by the end of October – has forced clinicians on the scene, such as those working with Médicins Sans Frontières (MSF; Doctors Without Borders), to try new approaches in their attempt to rein in further spread of the infection, said Dr. de Clerk, an epidemiologist and family physician who serves as a field coordinator for MSF specializing in viral hemorrhagic fevers. Right now, it is hard to predict when the outbreak will be brought under control, she said. To watch an interview in which she discusses containment strategies, click here.
Dr. de Cleck had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
VIENNA – The huge scope of the West African Ebola outbreak makes bringing it under control an unprecedented challenge with an uncertain outcome, Dr. Hilde de Clerck said in an interview during the International Meeting on Emerging Diseases and Surveillance.
The large number of people who have been infected with Ebola in the West African countries of Guinea, Sierra Leone, and Liberia – close to 14,000 identified cases by the end of October – has forced clinicians on the scene, such as those working with Médicins Sans Frontières (MSF; Doctors Without Borders), to try new approaches in their attempt to rein in further spread of the infection, said Dr. de Clerk, an epidemiologist and family physician who serves as a field coordinator for MSF specializing in viral hemorrhagic fevers. Right now, it is hard to predict when the outbreak will be brought under control, she said. To watch an interview in which she discusses containment strategies, click here.
Dr. de Cleck had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
VIENNA – The huge scope of the West African Ebola outbreak makes bringing it under control an unprecedented challenge with an uncertain outcome, Dr. Hilde de Clerck said in an interview during the International Meeting on Emerging Diseases and Surveillance.
The large number of people who have been infected with Ebola in the West African countries of Guinea, Sierra Leone, and Liberia – close to 14,000 identified cases by the end of October – has forced clinicians on the scene, such as those working with Médicins Sans Frontières (MSF; Doctors Without Borders), to try new approaches in their attempt to rein in further spread of the infection, said Dr. de Clerk, an epidemiologist and family physician who serves as a field coordinator for MSF specializing in viral hemorrhagic fevers. Right now, it is hard to predict when the outbreak will be brought under control, she said. To watch an interview in which she discusses containment strategies, click here.
Dr. de Cleck had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT IMED 2014
U.S. C. difficile mortality jumped sevenfold 1999-2008
VIENNA – U.S. deaths from Clostridium difficile infection jumped roughly sevenfold from 1999 to 2008, but in the ensuing years (2009-2012), remained stable at about the level first reached in 2008, according to analysis of cause-of-death data from the National Center for Health Statistics.
The increase occurred uniformly across all age groups older than 40 years; among patients 40 years or younger mortality from C. difficile infection remained low, at a rate at or below one death per one million people, Andrew Noymer, Ph.D., reported in a poster at the International Meeting on Emerging Diseases and Surveillance.
Among those patients aged 80 years or older, the mortality rate in recent years with C. difficile infection listed as the primary cause exceeded one death per 5,000 people, reported Dr. Noymer, a researcher in population health and disease prevention at the University of California, Irvine.
The mortality data provided no direct insight into the factors contributing to the rise in C. difficile deaths during 1999-2008, but previous reports documented an increased prevalence starting in 2000 of a “hypervirulent” strain of C. difficile circulating in North America and elsewhere (Critical Care 2008;12:203-10).
C. difficile infection as the underlying cause of death rose from less than one age-adjusted occurrence for every 200,000 people in 1999 to about 2.4 age-adjusted deaths per 100,000 in 2008, and then remained at about that level through 2012. Rates were similar in women and men.
When analyzed as any mention of C. difficile infection with another factor cited as the primary cause of death occurrences also rose roughly sevenfold from 1999 to 2008, from about one death for every 200,000 people to about 3.5 deaths per 100,000.
When C. difficile has been a contributing factor, the wide spectrum of causes of death that it can accompany “reads like a who’s who of conditions requiring inpatient clinical care,” Dr. Noymer said. “Given the nosocomial nature of C. difficile this is not surprising.”
The top three lethal conditions with C. difficile complication were atherosclerotic heart disease, chronic obstructive pulmonary disease, and septicemia.
Dr. Noymer had no disclosures.
VIENNA – U.S. deaths from Clostridium difficile infection jumped roughly sevenfold from 1999 to 2008, but in the ensuing years (2009-2012), remained stable at about the level first reached in 2008, according to analysis of cause-of-death data from the National Center for Health Statistics.
The increase occurred uniformly across all age groups older than 40 years; among patients 40 years or younger mortality from C. difficile infection remained low, at a rate at or below one death per one million people, Andrew Noymer, Ph.D., reported in a poster at the International Meeting on Emerging Diseases and Surveillance.
Among those patients aged 80 years or older, the mortality rate in recent years with C. difficile infection listed as the primary cause exceeded one death per 5,000 people, reported Dr. Noymer, a researcher in population health and disease prevention at the University of California, Irvine.
The mortality data provided no direct insight into the factors contributing to the rise in C. difficile deaths during 1999-2008, but previous reports documented an increased prevalence starting in 2000 of a “hypervirulent” strain of C. difficile circulating in North America and elsewhere (Critical Care 2008;12:203-10).
C. difficile infection as the underlying cause of death rose from less than one age-adjusted occurrence for every 200,000 people in 1999 to about 2.4 age-adjusted deaths per 100,000 in 2008, and then remained at about that level through 2012. Rates were similar in women and men.
When analyzed as any mention of C. difficile infection with another factor cited as the primary cause of death occurrences also rose roughly sevenfold from 1999 to 2008, from about one death for every 200,000 people to about 3.5 deaths per 100,000.
When C. difficile has been a contributing factor, the wide spectrum of causes of death that it can accompany “reads like a who’s who of conditions requiring inpatient clinical care,” Dr. Noymer said. “Given the nosocomial nature of C. difficile this is not surprising.”
The top three lethal conditions with C. difficile complication were atherosclerotic heart disease, chronic obstructive pulmonary disease, and septicemia.
Dr. Noymer had no disclosures.
VIENNA – U.S. deaths from Clostridium difficile infection jumped roughly sevenfold from 1999 to 2008, but in the ensuing years (2009-2012), remained stable at about the level first reached in 2008, according to analysis of cause-of-death data from the National Center for Health Statistics.
The increase occurred uniformly across all age groups older than 40 years; among patients 40 years or younger mortality from C. difficile infection remained low, at a rate at or below one death per one million people, Andrew Noymer, Ph.D., reported in a poster at the International Meeting on Emerging Diseases and Surveillance.
Among those patients aged 80 years or older, the mortality rate in recent years with C. difficile infection listed as the primary cause exceeded one death per 5,000 people, reported Dr. Noymer, a researcher in population health and disease prevention at the University of California, Irvine.
The mortality data provided no direct insight into the factors contributing to the rise in C. difficile deaths during 1999-2008, but previous reports documented an increased prevalence starting in 2000 of a “hypervirulent” strain of C. difficile circulating in North America and elsewhere (Critical Care 2008;12:203-10).
C. difficile infection as the underlying cause of death rose from less than one age-adjusted occurrence for every 200,000 people in 1999 to about 2.4 age-adjusted deaths per 100,000 in 2008, and then remained at about that level through 2012. Rates were similar in women and men.
When analyzed as any mention of C. difficile infection with another factor cited as the primary cause of death occurrences also rose roughly sevenfold from 1999 to 2008, from about one death for every 200,000 people to about 3.5 deaths per 100,000.
When C. difficile has been a contributing factor, the wide spectrum of causes of death that it can accompany “reads like a who’s who of conditions requiring inpatient clinical care,” Dr. Noymer said. “Given the nosocomial nature of C. difficile this is not surprising.”
The top three lethal conditions with C. difficile complication were atherosclerotic heart disease, chronic obstructive pulmonary disease, and septicemia.
Dr. Noymer had no disclosures.
AT IMED 2014
Key clinical point: During 1999-2008, U.S. deaths attributable to Clostridium difficile infection rose about sevenfold, and then plateaued at that high level through 2012.
Major finding: Age-adjusted C. difficile mortality was less than 1/200,000 in 1999 and about 2.4/100,000 in 2008.
Data source: Review of national mortality data collected by the U.S. National Center for Health Statistics.
Disclosures: Dr. Noymer had no disclosures.
Vedolizumab rated first line for ulcerative colitis
VIENNA – Vedolizumab, a second-line biologic for treating patients who have ulcerative colitis or Crohn’s disease and don’t respond to an anti-tumor necrosis factor drug, is gaining traction with experts who have used the drug investigationally for several years and consider vedolizumab to be their first-line biologic for ulcerative colitis. But they agree that for Crohn’s disease the available data support using vedolizumab as a second-line agent.
“I think vedolizumab [Entyvio] is a first-line biologic for ulcerative colitis. Full stop,” said Dr. Brian G. Feagan during a talk at the United European Gastroenterology Global Congress. He cited his 12-year experience using vedolizumab, which has compiled a strong record of efficacy as well as safety for ulcerative colitis.
“It’s the promise of a reduced risk of systemic adverse events, especially secondary infections,” by using vedolizumab instead of a drug that blocks tumor necrosis factor (TNF), said Dr. Feagan in an interview.
“For Crohn’s disease, vedolizumab seems to have a slower onset of action, so for sicker Crohn’s patients you may want to choose a TNF blocker,” said Dr. Feagan, a gastroenterologist and professor of medicine at the University of Western Ontario in London, Ont. “For Crohn’s disease you could use vedolizumab first in some patients and an anti-TNF first line in other patients.”
Another gastroenterologist experienced in using vedolizumab to treat inflammatory bowel diseases largely agreed. “Vedolizumab is a first-line biologic for ulcerative colitis, For Crohn’s disease, the anti-TNF drugs are still the way to go,” said Dr. Paul Rutgeerts, a gastroenterologist and professor of medicine at Catholic University in Leuven, Belgium.
Dr. Feagan and Dr. Rutgeerts as well as others cite a fundamental difference in the way vedolizumab mitigates autoimmunity compared with TNF blocking drugs as the likely explanation for why vedolizumab seems to work much better for ulcerative colitis than it does for Crohn’s disease.
As spelled out last year in an editorial by Dr. Fabio Cominelli (N. Engl. J. Med. 2013;369:775-6), vedolizumab specifically blocks the integrin that directs leukocytes to the gut musoca, and this limited, gut-specific action may explain why the drug has such a favorable adverse effect profile as well as why it is less effective at inducing remissions in Crohn’s disease, which can hit any site along the entire gastrointestinal tract and cause transmural fistulas and multi-organ involvement. In contrast, ulcerative colitis is limited to the superficial mucosa of the large bowel.
“With ulcerative colitis it is only the mucosa. Crohn’s disease is more of a transmural disorder that involves the entire wall of the gut so you have more need for systemic action, which is better delivered by anti-TNFs” than by vedolizumab, Dr. Rutgeerts said in an interview.
Perhaps vedolizumab’s only major drawback as first-line biologic treatment for ulcerative colitis and even for some Crohn’s disease patients is its high cost, especially at a time when the price for the anti-TNF drug infliximab has begun to fall following introduction of biosimilar infliximab in Europe and its expected appearance soon in the United States.
“The cost [of vedolizumab] is very high,” especially when administered every 4 weeks, which seems to be the dosage many patients need to maintain long-term responses and remissions, Dr. Rutgeerts said.
“Now we have biosimilar infliximab, which is cheaper than vedolizumab” and hence more attractive, at least for cost, noted Dr. C. Janneke van der Woude, head of the inflammatory bowel diseases unit at Erasmus University in Rotterdam, The Netherlands. She also noted that many patients prefer subcutaneous drug treatment with the anti-TNF agent adalimumab over intravenous treatments, which is the route for vedolizumab.
Two-year data show durable efficacy, safety
Vedolizumab demonstrated its ability to safely maintain remission in responsive patients with inflammatory bowel disease in results from long-term treatment and follow-up of patients enrolled in the pivotal phase III trials that supplied the data that led to vedolizumab’s marketing approval earlier this year in both the United States and in Europe.
Dr. Feagan presented outcome results after 80 and 104 weeks of vedolizumab treatment of 278 patients with ulcerative colitis who had completed a full year of treatment during the GEMINI 1 trial [Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Ulcerative Colitis] (N. Engl. J. Med. 2013;369:699-710). He reported that the percentage of patients in clinical remission grew from 66% after 52 weeks on treatment (the time of entry into the long-term phase of the study), to 77% after 80 weeks, which then dropped to 73% after 104 weeks. Patients with a clinical response increased from 78% after 52 weeks to 88% after 80 weeks, and then dropped to 83% after 104 weeks.
During weeks 53-104 on treatment the rates of adverse events, serious adverse events, serious infections, adverse events resulting in treatment discontinuation, enteric infections, and malignancies were all low and similar to the event rates seen among the patients randomized to placebo in the GEMINI 1 study. The same pattern of low event rates similar to the placebo patients also occurred for episodes of nasopharyngitis, upper respiratory tract infections, Clostridium difficile infections, and tuberculosis cases.
The results also showed better rates of long-term remission and response in the patients who had not previously failed treatment with an anti-TNF drug compared with those who had. Asked what might explain this, Dr. Feagan replied “we know that patients who fail prior drugs are always harder to treat.”
A very similar pattern occurred among the patients with Crohn’s disease who remained on vedolizumab for an additional 52 weeks following completion of a first year of treatment in the GEMINI 2 trial [the Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Crohn’s Disease], the pivotal, phase III study that led to the Crohn’s disease indication for vedolizumab (N. Engl. J. Med. 2013;369:711-21). Among 295 GEMINI 2 completer patients who remained on vedolizumab the rate of complete remissions was 57% at entry into the long-term study after 52 weeks on treatment, 64% after 80 weeks on treatment, and 61% after 104 weeks.The overall response rate was 81% at 52 weeks, 78% after 80 weeks, and 74% at 104 week, Dr. Rutgeerts reported. However, he noted that the study design allowed patients who experienced a flare to receive conventional rescue medications and still be counted a responder or in remission, which increased the number of patients in both of these two groups. “Patients did not need to be a responder or in remission at every time point,” he noted.
Once again, the rates of adverse events, serious adverse events, adverse events resulting in drug discontinuation, infections, serious infections, nasopharyngitis, and upper respiratory infection were all similar among patients on long-term vedolizumab compared with control patients with Crohn’s disease, Dr. Rutgeerts said.
The results suggest that with vedolizumab treatment of inflammatory bowel disease “once you achieve an effect it is long-lasting,” Dr. Rutgeerts said in an interview. But he cautioned that the long-lasting efficacy was achieved with treatment every 4 weeks. While this approach was safe, it would also be expensive in routine practice, he noted. “The safety looks good, but the cost would be very high.”
“A key concept of vedolizumab is that it builds efficacy over time,” commented Dr. Silvio Danese during a talk at the meeting. “Vedolizumab is not the fastest runner, but [treating inflammatory bowel disease] is a marathon, and the important thing is getting to the finish,” said Dr. Danese, head of the inflammatory bowel disease unit at the Humanitas Clinic and Research Center in Milan.
Dr. Danese also said that vedolizumab has a safety advantage over anti-TNF drugs when treating ulcerative colitis, although vedolizumab’s efficacy for treating steroid-refractory, fulminant ulcertative colitis remains untested. And he agreed that vedolizumab’s role as a go-to agent for inducing remission in active Crohn’s disease seems questionable.
Two other reports at the meeting further fleshed out vedolizumab’s performance in the GEMINI trials.
One analysis focused on 34 ulcerative colitis patients and 57 Crohn’s disease patients who responded to vedolizumab induction treatment but then lost their response when they subsequently received vedolizumab once every 8 weeks. These patients then switched to a regimen in which they received the drug every 4 weeks, and this resulted in significant reductions in disease activity among some of the ulcerative colitis and Crohn’s disease patients, reported Dr. Séverine Vermeire, a gastroenterologist and professor of medicine at Catholic University in Leuven.
She estimated that roughly a third of patients in both disease categories who lost response when put on the drug once every 8 weeks regained their complete response when their dosing frequency increased to once every 4 weeks.
The findings “suggest that dosing every 4 weeks may be beneficial for certain patients, with no apparent change in safety. These data provide insight into the potential value of dosing every 4 weeks, and in routine practice we will have patients who will lose response when they receive the drug every 8 weeks,” Dr. Vermeire said. “We should try to identify these patients early,” she said, and “we need to investigate why some patients lose their vedolizumab response.” The labeling for vedolizumab calls for treatment once every 8 weeks for maintenance.
Another analysis focused on the total of 1,443 inflammatory bowel disease patients who received vedolizumab for both induction and maintenance in the two GEMINI studies. This safety analysis examined the incidence of total infections and serious infections among patients who started on vedolizumab while on treatment with a corticosteroid, an immunomodulating drug, both of these agents, or neither of these agents.
The analysis showed similar rates of both total infections and serious infections in all four subgroups, suggesting no interaction between vedsolizumab and other immuno-active drugs in terms of vulnerability to infection, said Dr. Jean-Frédréic Colombel, professor of medicine and director of the inflammatory bowel disease center at Mount Sinai Medical Center in New York.
The low rate of serious infections, which occurred at 0.04-0.06 infections/person-year of follow-up was “reassuring,” said Dr. Colombel, but these infections were also so rare that it limited interpretation of the findings. He also noted that the analysis only focused on concomitant drugs at the time patients began vedolizumab treatment and did not take into account subsequent medication changes.
The GEMINI 1 and 2 trials were sponsored by Takeda, the company that markets vedolizumab (Entyvio). Dr. Feagan has been a consultant to Takeda, AbbVie, Merck, and UCB. Dr. Rutgeerts has been a consultant to Takeda, AbbVie, Janssen, Merch, and UCB. Dr. van der Woude has been an advisor to Dr. Falk, Abbvie, Janssen, Johnson&Johnson, and Cosmo. Dr. Danese has been a consultant to Takeda and to several other companies. Dr. Vermeire has been a consultant to Takeda and to several other companies. Dr. Colombel has been a consultant to Takeda and to several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AGA Resources
• IBD Clinical Service Line: www.gastro.org/practice/clinical-service-line/ibd-
clinical-service-line
• Clinical Decision Support Tool: Use of Biologic Drugs for Inflammatory Crohn’s Disease: http://campaigns.gastro.org/algorithms/crohns
VIENNA – Vedolizumab, a second-line biologic for treating patients who have ulcerative colitis or Crohn’s disease and don’t respond to an anti-tumor necrosis factor drug, is gaining traction with experts who have used the drug investigationally for several years and consider vedolizumab to be their first-line biologic for ulcerative colitis. But they agree that for Crohn’s disease the available data support using vedolizumab as a second-line agent.
“I think vedolizumab [Entyvio] is a first-line biologic for ulcerative colitis. Full stop,” said Dr. Brian G. Feagan during a talk at the United European Gastroenterology Global Congress. He cited his 12-year experience using vedolizumab, which has compiled a strong record of efficacy as well as safety for ulcerative colitis.
“It’s the promise of a reduced risk of systemic adverse events, especially secondary infections,” by using vedolizumab instead of a drug that blocks tumor necrosis factor (TNF), said Dr. Feagan in an interview.
“For Crohn’s disease, vedolizumab seems to have a slower onset of action, so for sicker Crohn’s patients you may want to choose a TNF blocker,” said Dr. Feagan, a gastroenterologist and professor of medicine at the University of Western Ontario in London, Ont. “For Crohn’s disease you could use vedolizumab first in some patients and an anti-TNF first line in other patients.”
Another gastroenterologist experienced in using vedolizumab to treat inflammatory bowel diseases largely agreed. “Vedolizumab is a first-line biologic for ulcerative colitis, For Crohn’s disease, the anti-TNF drugs are still the way to go,” said Dr. Paul Rutgeerts, a gastroenterologist and professor of medicine at Catholic University in Leuven, Belgium.
Dr. Feagan and Dr. Rutgeerts as well as others cite a fundamental difference in the way vedolizumab mitigates autoimmunity compared with TNF blocking drugs as the likely explanation for why vedolizumab seems to work much better for ulcerative colitis than it does for Crohn’s disease.
As spelled out last year in an editorial by Dr. Fabio Cominelli (N. Engl. J. Med. 2013;369:775-6), vedolizumab specifically blocks the integrin that directs leukocytes to the gut musoca, and this limited, gut-specific action may explain why the drug has such a favorable adverse effect profile as well as why it is less effective at inducing remissions in Crohn’s disease, which can hit any site along the entire gastrointestinal tract and cause transmural fistulas and multi-organ involvement. In contrast, ulcerative colitis is limited to the superficial mucosa of the large bowel.
“With ulcerative colitis it is only the mucosa. Crohn’s disease is more of a transmural disorder that involves the entire wall of the gut so you have more need for systemic action, which is better delivered by anti-TNFs” than by vedolizumab, Dr. Rutgeerts said in an interview.
Perhaps vedolizumab’s only major drawback as first-line biologic treatment for ulcerative colitis and even for some Crohn’s disease patients is its high cost, especially at a time when the price for the anti-TNF drug infliximab has begun to fall following introduction of biosimilar infliximab in Europe and its expected appearance soon in the United States.
“The cost [of vedolizumab] is very high,” especially when administered every 4 weeks, which seems to be the dosage many patients need to maintain long-term responses and remissions, Dr. Rutgeerts said.
“Now we have biosimilar infliximab, which is cheaper than vedolizumab” and hence more attractive, at least for cost, noted Dr. C. Janneke van der Woude, head of the inflammatory bowel diseases unit at Erasmus University in Rotterdam, The Netherlands. She also noted that many patients prefer subcutaneous drug treatment with the anti-TNF agent adalimumab over intravenous treatments, which is the route for vedolizumab.
Two-year data show durable efficacy, safety
Vedolizumab demonstrated its ability to safely maintain remission in responsive patients with inflammatory bowel disease in results from long-term treatment and follow-up of patients enrolled in the pivotal phase III trials that supplied the data that led to vedolizumab’s marketing approval earlier this year in both the United States and in Europe.
Dr. Feagan presented outcome results after 80 and 104 weeks of vedolizumab treatment of 278 patients with ulcerative colitis who had completed a full year of treatment during the GEMINI 1 trial [Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Ulcerative Colitis] (N. Engl. J. Med. 2013;369:699-710). He reported that the percentage of patients in clinical remission grew from 66% after 52 weeks on treatment (the time of entry into the long-term phase of the study), to 77% after 80 weeks, which then dropped to 73% after 104 weeks. Patients with a clinical response increased from 78% after 52 weeks to 88% after 80 weeks, and then dropped to 83% after 104 weeks.
During weeks 53-104 on treatment the rates of adverse events, serious adverse events, serious infections, adverse events resulting in treatment discontinuation, enteric infections, and malignancies were all low and similar to the event rates seen among the patients randomized to placebo in the GEMINI 1 study. The same pattern of low event rates similar to the placebo patients also occurred for episodes of nasopharyngitis, upper respiratory tract infections, Clostridium difficile infections, and tuberculosis cases.
The results also showed better rates of long-term remission and response in the patients who had not previously failed treatment with an anti-TNF drug compared with those who had. Asked what might explain this, Dr. Feagan replied “we know that patients who fail prior drugs are always harder to treat.”
A very similar pattern occurred among the patients with Crohn’s disease who remained on vedolizumab for an additional 52 weeks following completion of a first year of treatment in the GEMINI 2 trial [the Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Crohn’s Disease], the pivotal, phase III study that led to the Crohn’s disease indication for vedolizumab (N. Engl. J. Med. 2013;369:711-21). Among 295 GEMINI 2 completer patients who remained on vedolizumab the rate of complete remissions was 57% at entry into the long-term study after 52 weeks on treatment, 64% after 80 weeks on treatment, and 61% after 104 weeks.The overall response rate was 81% at 52 weeks, 78% after 80 weeks, and 74% at 104 week, Dr. Rutgeerts reported. However, he noted that the study design allowed patients who experienced a flare to receive conventional rescue medications and still be counted a responder or in remission, which increased the number of patients in both of these two groups. “Patients did not need to be a responder or in remission at every time point,” he noted.
Once again, the rates of adverse events, serious adverse events, adverse events resulting in drug discontinuation, infections, serious infections, nasopharyngitis, and upper respiratory infection were all similar among patients on long-term vedolizumab compared with control patients with Crohn’s disease, Dr. Rutgeerts said.
The results suggest that with vedolizumab treatment of inflammatory bowel disease “once you achieve an effect it is long-lasting,” Dr. Rutgeerts said in an interview. But he cautioned that the long-lasting efficacy was achieved with treatment every 4 weeks. While this approach was safe, it would also be expensive in routine practice, he noted. “The safety looks good, but the cost would be very high.”
“A key concept of vedolizumab is that it builds efficacy over time,” commented Dr. Silvio Danese during a talk at the meeting. “Vedolizumab is not the fastest runner, but [treating inflammatory bowel disease] is a marathon, and the important thing is getting to the finish,” said Dr. Danese, head of the inflammatory bowel disease unit at the Humanitas Clinic and Research Center in Milan.
Dr. Danese also said that vedolizumab has a safety advantage over anti-TNF drugs when treating ulcerative colitis, although vedolizumab’s efficacy for treating steroid-refractory, fulminant ulcertative colitis remains untested. And he agreed that vedolizumab’s role as a go-to agent for inducing remission in active Crohn’s disease seems questionable.
Two other reports at the meeting further fleshed out vedolizumab’s performance in the GEMINI trials.
One analysis focused on 34 ulcerative colitis patients and 57 Crohn’s disease patients who responded to vedolizumab induction treatment but then lost their response when they subsequently received vedolizumab once every 8 weeks. These patients then switched to a regimen in which they received the drug every 4 weeks, and this resulted in significant reductions in disease activity among some of the ulcerative colitis and Crohn’s disease patients, reported Dr. Séverine Vermeire, a gastroenterologist and professor of medicine at Catholic University in Leuven.
She estimated that roughly a third of patients in both disease categories who lost response when put on the drug once every 8 weeks regained their complete response when their dosing frequency increased to once every 4 weeks.
The findings “suggest that dosing every 4 weeks may be beneficial for certain patients, with no apparent change in safety. These data provide insight into the potential value of dosing every 4 weeks, and in routine practice we will have patients who will lose response when they receive the drug every 8 weeks,” Dr. Vermeire said. “We should try to identify these patients early,” she said, and “we need to investigate why some patients lose their vedolizumab response.” The labeling for vedolizumab calls for treatment once every 8 weeks for maintenance.
Another analysis focused on the total of 1,443 inflammatory bowel disease patients who received vedolizumab for both induction and maintenance in the two GEMINI studies. This safety analysis examined the incidence of total infections and serious infections among patients who started on vedolizumab while on treatment with a corticosteroid, an immunomodulating drug, both of these agents, or neither of these agents.
The analysis showed similar rates of both total infections and serious infections in all four subgroups, suggesting no interaction between vedsolizumab and other immuno-active drugs in terms of vulnerability to infection, said Dr. Jean-Frédréic Colombel, professor of medicine and director of the inflammatory bowel disease center at Mount Sinai Medical Center in New York.
The low rate of serious infections, which occurred at 0.04-0.06 infections/person-year of follow-up was “reassuring,” said Dr. Colombel, but these infections were also so rare that it limited interpretation of the findings. He also noted that the analysis only focused on concomitant drugs at the time patients began vedolizumab treatment and did not take into account subsequent medication changes.
The GEMINI 1 and 2 trials were sponsored by Takeda, the company that markets vedolizumab (Entyvio). Dr. Feagan has been a consultant to Takeda, AbbVie, Merck, and UCB. Dr. Rutgeerts has been a consultant to Takeda, AbbVie, Janssen, Merch, and UCB. Dr. van der Woude has been an advisor to Dr. Falk, Abbvie, Janssen, Johnson&Johnson, and Cosmo. Dr. Danese has been a consultant to Takeda and to several other companies. Dr. Vermeire has been a consultant to Takeda and to several other companies. Dr. Colombel has been a consultant to Takeda and to several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AGA Resources
• IBD Clinical Service Line: www.gastro.org/practice/clinical-service-line/ibd-
clinical-service-line
• Clinical Decision Support Tool: Use of Biologic Drugs for Inflammatory Crohn’s Disease: http://campaigns.gastro.org/algorithms/crohns
VIENNA – Vedolizumab, a second-line biologic for treating patients who have ulcerative colitis or Crohn’s disease and don’t respond to an anti-tumor necrosis factor drug, is gaining traction with experts who have used the drug investigationally for several years and consider vedolizumab to be their first-line biologic for ulcerative colitis. But they agree that for Crohn’s disease the available data support using vedolizumab as a second-line agent.
“I think vedolizumab [Entyvio] is a first-line biologic for ulcerative colitis. Full stop,” said Dr. Brian G. Feagan during a talk at the United European Gastroenterology Global Congress. He cited his 12-year experience using vedolizumab, which has compiled a strong record of efficacy as well as safety for ulcerative colitis.
“It’s the promise of a reduced risk of systemic adverse events, especially secondary infections,” by using vedolizumab instead of a drug that blocks tumor necrosis factor (TNF), said Dr. Feagan in an interview.
“For Crohn’s disease, vedolizumab seems to have a slower onset of action, so for sicker Crohn’s patients you may want to choose a TNF blocker,” said Dr. Feagan, a gastroenterologist and professor of medicine at the University of Western Ontario in London, Ont. “For Crohn’s disease you could use vedolizumab first in some patients and an anti-TNF first line in other patients.”
Another gastroenterologist experienced in using vedolizumab to treat inflammatory bowel diseases largely agreed. “Vedolizumab is a first-line biologic for ulcerative colitis, For Crohn’s disease, the anti-TNF drugs are still the way to go,” said Dr. Paul Rutgeerts, a gastroenterologist and professor of medicine at Catholic University in Leuven, Belgium.
Dr. Feagan and Dr. Rutgeerts as well as others cite a fundamental difference in the way vedolizumab mitigates autoimmunity compared with TNF blocking drugs as the likely explanation for why vedolizumab seems to work much better for ulcerative colitis than it does for Crohn’s disease.
As spelled out last year in an editorial by Dr. Fabio Cominelli (N. Engl. J. Med. 2013;369:775-6), vedolizumab specifically blocks the integrin that directs leukocytes to the gut musoca, and this limited, gut-specific action may explain why the drug has such a favorable adverse effect profile as well as why it is less effective at inducing remissions in Crohn’s disease, which can hit any site along the entire gastrointestinal tract and cause transmural fistulas and multi-organ involvement. In contrast, ulcerative colitis is limited to the superficial mucosa of the large bowel.
“With ulcerative colitis it is only the mucosa. Crohn’s disease is more of a transmural disorder that involves the entire wall of the gut so you have more need for systemic action, which is better delivered by anti-TNFs” than by vedolizumab, Dr. Rutgeerts said in an interview.
Perhaps vedolizumab’s only major drawback as first-line biologic treatment for ulcerative colitis and even for some Crohn’s disease patients is its high cost, especially at a time when the price for the anti-TNF drug infliximab has begun to fall following introduction of biosimilar infliximab in Europe and its expected appearance soon in the United States.
“The cost [of vedolizumab] is very high,” especially when administered every 4 weeks, which seems to be the dosage many patients need to maintain long-term responses and remissions, Dr. Rutgeerts said.
“Now we have biosimilar infliximab, which is cheaper than vedolizumab” and hence more attractive, at least for cost, noted Dr. C. Janneke van der Woude, head of the inflammatory bowel diseases unit at Erasmus University in Rotterdam, The Netherlands. She also noted that many patients prefer subcutaneous drug treatment with the anti-TNF agent adalimumab over intravenous treatments, which is the route for vedolizumab.
Two-year data show durable efficacy, safety
Vedolizumab demonstrated its ability to safely maintain remission in responsive patients with inflammatory bowel disease in results from long-term treatment and follow-up of patients enrolled in the pivotal phase III trials that supplied the data that led to vedolizumab’s marketing approval earlier this year in both the United States and in Europe.
Dr. Feagan presented outcome results after 80 and 104 weeks of vedolizumab treatment of 278 patients with ulcerative colitis who had completed a full year of treatment during the GEMINI 1 trial [Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Ulcerative Colitis] (N. Engl. J. Med. 2013;369:699-710). He reported that the percentage of patients in clinical remission grew from 66% after 52 weeks on treatment (the time of entry into the long-term phase of the study), to 77% after 80 weeks, which then dropped to 73% after 104 weeks. Patients with a clinical response increased from 78% after 52 weeks to 88% after 80 weeks, and then dropped to 83% after 104 weeks.
During weeks 53-104 on treatment the rates of adverse events, serious adverse events, serious infections, adverse events resulting in treatment discontinuation, enteric infections, and malignancies were all low and similar to the event rates seen among the patients randomized to placebo in the GEMINI 1 study. The same pattern of low event rates similar to the placebo patients also occurred for episodes of nasopharyngitis, upper respiratory tract infections, Clostridium difficile infections, and tuberculosis cases.
The results also showed better rates of long-term remission and response in the patients who had not previously failed treatment with an anti-TNF drug compared with those who had. Asked what might explain this, Dr. Feagan replied “we know that patients who fail prior drugs are always harder to treat.”
A very similar pattern occurred among the patients with Crohn’s disease who remained on vedolizumab for an additional 52 weeks following completion of a first year of treatment in the GEMINI 2 trial [the Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Crohn’s Disease], the pivotal, phase III study that led to the Crohn’s disease indication for vedolizumab (N. Engl. J. Med. 2013;369:711-21). Among 295 GEMINI 2 completer patients who remained on vedolizumab the rate of complete remissions was 57% at entry into the long-term study after 52 weeks on treatment, 64% after 80 weeks on treatment, and 61% after 104 weeks.The overall response rate was 81% at 52 weeks, 78% after 80 weeks, and 74% at 104 week, Dr. Rutgeerts reported. However, he noted that the study design allowed patients who experienced a flare to receive conventional rescue medications and still be counted a responder or in remission, which increased the number of patients in both of these two groups. “Patients did not need to be a responder or in remission at every time point,” he noted.
Once again, the rates of adverse events, serious adverse events, adverse events resulting in drug discontinuation, infections, serious infections, nasopharyngitis, and upper respiratory infection were all similar among patients on long-term vedolizumab compared with control patients with Crohn’s disease, Dr. Rutgeerts said.
The results suggest that with vedolizumab treatment of inflammatory bowel disease “once you achieve an effect it is long-lasting,” Dr. Rutgeerts said in an interview. But he cautioned that the long-lasting efficacy was achieved with treatment every 4 weeks. While this approach was safe, it would also be expensive in routine practice, he noted. “The safety looks good, but the cost would be very high.”
“A key concept of vedolizumab is that it builds efficacy over time,” commented Dr. Silvio Danese during a talk at the meeting. “Vedolizumab is not the fastest runner, but [treating inflammatory bowel disease] is a marathon, and the important thing is getting to the finish,” said Dr. Danese, head of the inflammatory bowel disease unit at the Humanitas Clinic and Research Center in Milan.
Dr. Danese also said that vedolizumab has a safety advantage over anti-TNF drugs when treating ulcerative colitis, although vedolizumab’s efficacy for treating steroid-refractory, fulminant ulcertative colitis remains untested. And he agreed that vedolizumab’s role as a go-to agent for inducing remission in active Crohn’s disease seems questionable.
Two other reports at the meeting further fleshed out vedolizumab’s performance in the GEMINI trials.
One analysis focused on 34 ulcerative colitis patients and 57 Crohn’s disease patients who responded to vedolizumab induction treatment but then lost their response when they subsequently received vedolizumab once every 8 weeks. These patients then switched to a regimen in which they received the drug every 4 weeks, and this resulted in significant reductions in disease activity among some of the ulcerative colitis and Crohn’s disease patients, reported Dr. Séverine Vermeire, a gastroenterologist and professor of medicine at Catholic University in Leuven.
She estimated that roughly a third of patients in both disease categories who lost response when put on the drug once every 8 weeks regained their complete response when their dosing frequency increased to once every 4 weeks.
The findings “suggest that dosing every 4 weeks may be beneficial for certain patients, with no apparent change in safety. These data provide insight into the potential value of dosing every 4 weeks, and in routine practice we will have patients who will lose response when they receive the drug every 8 weeks,” Dr. Vermeire said. “We should try to identify these patients early,” she said, and “we need to investigate why some patients lose their vedolizumab response.” The labeling for vedolizumab calls for treatment once every 8 weeks for maintenance.
Another analysis focused on the total of 1,443 inflammatory bowel disease patients who received vedolizumab for both induction and maintenance in the two GEMINI studies. This safety analysis examined the incidence of total infections and serious infections among patients who started on vedolizumab while on treatment with a corticosteroid, an immunomodulating drug, both of these agents, or neither of these agents.
The analysis showed similar rates of both total infections and serious infections in all four subgroups, suggesting no interaction between vedsolizumab and other immuno-active drugs in terms of vulnerability to infection, said Dr. Jean-Frédréic Colombel, professor of medicine and director of the inflammatory bowel disease center at Mount Sinai Medical Center in New York.
The low rate of serious infections, which occurred at 0.04-0.06 infections/person-year of follow-up was “reassuring,” said Dr. Colombel, but these infections were also so rare that it limited interpretation of the findings. He also noted that the analysis only focused on concomitant drugs at the time patients began vedolizumab treatment and did not take into account subsequent medication changes.
The GEMINI 1 and 2 trials were sponsored by Takeda, the company that markets vedolizumab (Entyvio). Dr. Feagan has been a consultant to Takeda, AbbVie, Merck, and UCB. Dr. Rutgeerts has been a consultant to Takeda, AbbVie, Janssen, Merch, and UCB. Dr. van der Woude has been an advisor to Dr. Falk, Abbvie, Janssen, Johnson&Johnson, and Cosmo. Dr. Danese has been a consultant to Takeda and to several other companies. Dr. Vermeire has been a consultant to Takeda and to several other companies. Dr. Colombel has been a consultant to Takeda and to several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AGA Resources
• IBD Clinical Service Line: www.gastro.org/practice/clinical-service-line/ibd-
clinical-service-line
• Clinical Decision Support Tool: Use of Biologic Drugs for Inflammatory Crohn’s Disease: http://campaigns.gastro.org/algorithms/crohns
EXPERT ANALYSIS FROM UEG WEEK VIENNA 2014
Vedolizumab rated first line for ulcerative colitis
VIENNA – Vedolizumab, a second-line biologic for treating patients who have ulcerative colitis or Crohn’s disease and don’t respond to an anti-tumor necrosis factor drug, is gaining traction with experts who have used the drug investigationally for several years and consider vedolizumab to be their first-line biologic for ulcerative colitis. But they agree that for Crohn’s disease the available data support using vedolizumab as a second-line agent.
“I think vedolizumab [Entyvio] is a first-line biologic for ulcerative colitis. Full stop,” said Dr. Brian G. Feagan during a talk at the United European Gastroenterology Global Congress. He cited his 12-year experience using vedolizumab, which has compiled a strong record of efficacy as well as safety for ulcerative colitis.
“It’s the promise of a reduced risk of systemic adverse events, especially secondary infections,” by using vedolizumab instead of a drug that blocks tumor necrosis factor (TNF), said Dr. Feagan in an interview.
“For Crohn’s disease, vedolizumab seems to have a slower onset of action, so for sicker Crohn’s patients you may want to choose a TNF blocker,” said Dr. Feagan, a gastroenterologist and professor of medicine at the University of Western Ontario in London, Ont. “For Crohn’s disease you could use vedolizumab first in some patients and an anti-TNF first line in other patients.”
Another gastroenterologist experienced in using vedolizumab to treat inflammatory bowel diseases largely agreed. “Vedolizumab is a first-line biologic for ulcerative colitis, For Crohn’s disease, the anti-TNF drugs are still the way to go,” said Dr. Paul Rutgeerts, a gastroenterologist and professor of medicine at Catholic University in Leuven, Belgium.
Dr. Feagan and Dr. Rutgeerts as well as others cite a fundamental difference in the way vedolizumab mitigates autoimmunity compared with TNF blocking drugs as the likely explanation for why vedolizumab seems to work much better for ulcerative colitis than it does for Crohn’s disease.
As spelled out last year in an editorial by Dr. Fabio Cominelli (N. Engl. J. Med. 2013;369:775-6), vedolizumab specifically blocks the integrin that directs leukocytes to the gut musoca, and this limited, gut-specific action may explain why the drug has such a favorable adverse effect profile as well as why it is less effective at inducing remissions in Crohn’s disease, which can hit any site along the entire gastrointestinal tract and cause transmural fistulas and multi-organ involvement. In contrast, ulcerative colitis is limited to the superficial mucosa of the large bowel.
“With ulcerative colitis it is only the mucosa. Crohn’s disease is more of a transmural disorder that involves the entire wall of the gut so you have more need for systemic action, which is better delivered by anti-TNFs” than by vedolizumab, Dr. Rutgeerts said in an interview.
Perhaps vedolizumab’s only major drawback as first-line biologic treatment for ulcerative colitis and even for some Crohn’s disease patients is its high cost, especially at a time when the price for the anti-TNF drug infliximab has begun to fall following introduction of biosimilar infliximab in Europe and its expected appearance soon in the United States.
“The cost [of vedolizumab] is very high,” especially when administered every 4 weeks, which seems to be the dosage many patients need to maintain long-term responses and remissions, Dr. Rutgeerts said.
“Now we have biosimilar infliximab, which is cheaper than vedolizumab” and hence more attractive, at least for cost, noted Dr. C. Janneke van der Woude, head of the inflammatory bowel diseases unit at Erasmus University in Rotterdam, The Netherlands. She also noted that many patients prefer subcutaneous drug treatment with the anti-TNF agent adalimumab over intravenous treatments, which is the route for vedolizumab.
Two-year data show durable efficacy, safety
Vedolizumab demonstrated its ability to safely maintain remission in responsive patients with inflammatory bowel disease in results from long-term treatment and follow-up of patients enrolled in the pivotal phase III trials that supplied the data that led to vedolizumab’s marketing approval earlier this year in both the United States and in Europe.
Dr. Feagan presented outcome results after 80 and 104 weeks of vedolizumab treatment of 278 patients with ulcerative colitis who had completed a full year of treatment during the GEMINI 1 trial [Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Ulcerative Colitis] (N. Engl. J. Med. 2013;369:699-710). He reported that the percentage of patients in clinical remission grew from 66% after 52 weeks on treatment (the time of entry into the long-term phase of the study), to 77% after 80 weeks, which then dropped to 73% after 104 weeks. Patients with a clinical response increased from 78% after 52 weeks to 88% after 80 weeks, and then dropped to 83% after 104 weeks.
During weeks 53-104 on treatment the rates of adverse events, serious adverse events, serious infections, adverse events resulting in treatment discontinuation, enteric infections, and malignancies were all low and similar to the event rates seen among the patients randomized to placebo in the GEMINI 1 study. The same pattern of low event rates similar to the placebo patients also occurred for episodes of nasopharyngitis, upper respiratory tract infections, Clostridium difficile infections, and tuberculosis cases.
The results also showed better rates of long-term remission and response in the patients who had not previously failed treatment with an anti-TNF drug compared with those who had. Asked what might explain this, Dr. Feagan replied “we know that patients who fail prior drugs are always harder to treat.”
A very similar pattern occurred among the patients with Crohn’s disease who remained on vedolizumab for an additional 52 weeks following completion of a first year of treatment in the GEMINI 2 trial [the Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Crohn’s Disease], the pivotal, phase III study that led to the Crohn’s disease indication for vedolizumab (N. Engl. J. Med. 2013;369:711-21). Among 295 GEMINI 2 completer patients who remained on vedolizumab the rate of complete remissions was 57% at entry into the long-term study after 52 weeks on treatment, 64% after 80 weeks on treatment, and 61% after 104 weeks.The overall response rate was 81% at 52 weeks, 78% after 80 weeks, and 74% at 104 week, Dr. Rutgeerts reported. However, he noted that the study design allowed patients who experienced a flare to receive conventional rescue medications and still be counted a responder or in remission, which increased the number of patients in both of these two groups. “Patients did not need to be a responder or in remission at every time point,” he noted.
Once again, the rates of adverse events, serious adverse events, adverse events resulting in drug discontinuation, infections, serious infections, nasopharyngitis, and upper respiratory infection were all similar among patients on long-term vedolizumab compared with control patients with Crohn’s disease, Dr. Rutgeerts said.
The results suggest that with vedolizumab treatment of inflammatory bowel disease “once you achieve an effect it is long-lasting,” Dr. Rutgeerts said in an interview. But he cautioned that the long-lasting efficacy was achieved with treatment every 4 weeks. While this approach was safe, it would also be expensive in routine practice, he noted. “The safety looks good, but the cost would be very high.”
“A key concept of vedolizumab is that it builds efficacy over time,” commented Dr. Silvio Danese during a talk at the meeting. “Vedolizumab is not the fastest runner, but [treating inflammatory bowel disease] is a marathon, and the important thing is getting to the finish,” said Dr. Danese, head of the inflammatory bowel disease unit at the Humanitas Clinic and Research Center in Milan.
Dr. Danese also said that vedolizumab has a safety advantage over anti-TNF drugs when treating ulcerative colitis, although vedolizumab’s efficacy for treating steroid-refractory, fulminant ulcertative colitis remains untested. And he agreed that vedolizumab’s role as a go-to agent for inducing remission in active Crohn’s disease seems questionable.
Two other reports at the meeting further fleshed out vedolizumab’s performance in the GEMINI trials.
One analysis focused on 34 ulcerative colitis patients and 57 Crohn’s disease patients who responded to vedolizumab induction treatment but then lost their response when they subsequently received vedolizumab once every 8 weeks. These patients then switched to a regimen in which they received the drug every 4 weeks, and this resulted in significant reductions in disease activity among some of the ulcerative colitis and Crohn’s disease patients, reported Dr. Séverine Vermeire, a gastroenterologist and professor of medicine at Catholic University in Leuven.
She estimated that roughly a third of patients in both disease categories who lost response when put on the drug once every 8 weeks regained their complete response when their dosing frequency increased to once every 4 weeks.
The findings “suggest that dosing every 4 weeks may be beneficial for certain patients, with no apparent change in safety. These data provide insight into the potential value of dosing every 4 weeks, and in routine practice we will have patients who will lose response when they receive the drug every 8 weeks,” Dr. Vermeire said. “We should try to identify these patients early,” she said, and “we need to investigate why some patients lose their vedolizumab response.” The labeling for vedolizumab calls for treatment once every 8 weeks for maintenance.
Another analysis focused on the total of 1,443 inflammatory bowel disease patients who received vedolizumab for both induction and maintenance in the two GEMINI studies. This safety analysis examined the incidence of total infections and serious infections among patients who started on vedolizumab while on treatment with a corticosteroid, an immunomodulating drug, both of these agents, or neither of these agents.
The analysis showed similar rates of both total infections and serious infections in all four subgroups, suggesting no interaction between vedsolizumab and other immuno-active drugs in terms of vulnerability to infection, said Dr. Jean-Frédréic Colombel, professor of medicine and director of the inflammatory bowel disease center at Mount Sinai Medical Center in New York.
The low rate of serious infections, which occurred at 0.04-0.06 infections/person-year of follow-up was “reassuring,” said Dr. Colombel, but these infections were also so rare that it limited interpretation of the findings. He also noted that the analysis only focused on concomitant drugs at the time patients began vedolizumab treatment and did not take into account subsequent medication changes.
The GEMINI 1 and 2 trials were sponsored by Takeda, the company that markets vedolizumab (Entyvio). Dr. Feagan has been a consultant to Takeda, AbbVie, Merck, and UCB. Dr. Rutgeerts has been a consultant to Takeda, AbbVie, Janssen, Merch, and UCB. Dr. van der Woude has been an advisor to Dr. Falk, Abbvie, Janssen, Johnson&Johnson, and Cosmo. Dr. Danese has been a consultant to Takeda and to several other companies. Dr. Vermeire has been a consultant to Takeda and to several other companies. Dr. Colombel has been a consultant to Takeda and to several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – Vedolizumab, a second-line biologic for treating patients who have ulcerative colitis or Crohn’s disease and don’t respond to an anti-tumor necrosis factor drug, is gaining traction with experts who have used the drug investigationally for several years and consider vedolizumab to be their first-line biologic for ulcerative colitis. But they agree that for Crohn’s disease the available data support using vedolizumab as a second-line agent.
“I think vedolizumab [Entyvio] is a first-line biologic for ulcerative colitis. Full stop,” said Dr. Brian G. Feagan during a talk at the United European Gastroenterology Global Congress. He cited his 12-year experience using vedolizumab, which has compiled a strong record of efficacy as well as safety for ulcerative colitis.
“It’s the promise of a reduced risk of systemic adverse events, especially secondary infections,” by using vedolizumab instead of a drug that blocks tumor necrosis factor (TNF), said Dr. Feagan in an interview.
“For Crohn’s disease, vedolizumab seems to have a slower onset of action, so for sicker Crohn’s patients you may want to choose a TNF blocker,” said Dr. Feagan, a gastroenterologist and professor of medicine at the University of Western Ontario in London, Ont. “For Crohn’s disease you could use vedolizumab first in some patients and an anti-TNF first line in other patients.”
Another gastroenterologist experienced in using vedolizumab to treat inflammatory bowel diseases largely agreed. “Vedolizumab is a first-line biologic for ulcerative colitis, For Crohn’s disease, the anti-TNF drugs are still the way to go,” said Dr. Paul Rutgeerts, a gastroenterologist and professor of medicine at Catholic University in Leuven, Belgium.
Dr. Feagan and Dr. Rutgeerts as well as others cite a fundamental difference in the way vedolizumab mitigates autoimmunity compared with TNF blocking drugs as the likely explanation for why vedolizumab seems to work much better for ulcerative colitis than it does for Crohn’s disease.
As spelled out last year in an editorial by Dr. Fabio Cominelli (N. Engl. J. Med. 2013;369:775-6), vedolizumab specifically blocks the integrin that directs leukocytes to the gut musoca, and this limited, gut-specific action may explain why the drug has such a favorable adverse effect profile as well as why it is less effective at inducing remissions in Crohn’s disease, which can hit any site along the entire gastrointestinal tract and cause transmural fistulas and multi-organ involvement. In contrast, ulcerative colitis is limited to the superficial mucosa of the large bowel.
“With ulcerative colitis it is only the mucosa. Crohn’s disease is more of a transmural disorder that involves the entire wall of the gut so you have more need for systemic action, which is better delivered by anti-TNFs” than by vedolizumab, Dr. Rutgeerts said in an interview.
Perhaps vedolizumab’s only major drawback as first-line biologic treatment for ulcerative colitis and even for some Crohn’s disease patients is its high cost, especially at a time when the price for the anti-TNF drug infliximab has begun to fall following introduction of biosimilar infliximab in Europe and its expected appearance soon in the United States.
“The cost [of vedolizumab] is very high,” especially when administered every 4 weeks, which seems to be the dosage many patients need to maintain long-term responses and remissions, Dr. Rutgeerts said.
“Now we have biosimilar infliximab, which is cheaper than vedolizumab” and hence more attractive, at least for cost, noted Dr. C. Janneke van der Woude, head of the inflammatory bowel diseases unit at Erasmus University in Rotterdam, The Netherlands. She also noted that many patients prefer subcutaneous drug treatment with the anti-TNF agent adalimumab over intravenous treatments, which is the route for vedolizumab.
Two-year data show durable efficacy, safety
Vedolizumab demonstrated its ability to safely maintain remission in responsive patients with inflammatory bowel disease in results from long-term treatment and follow-up of patients enrolled in the pivotal phase III trials that supplied the data that led to vedolizumab’s marketing approval earlier this year in both the United States and in Europe.
Dr. Feagan presented outcome results after 80 and 104 weeks of vedolizumab treatment of 278 patients with ulcerative colitis who had completed a full year of treatment during the GEMINI 1 trial [Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Ulcerative Colitis] (N. Engl. J. Med. 2013;369:699-710). He reported that the percentage of patients in clinical remission grew from 66% after 52 weeks on treatment (the time of entry into the long-term phase of the study), to 77% after 80 weeks, which then dropped to 73% after 104 weeks. Patients with a clinical response increased from 78% after 52 weeks to 88% after 80 weeks, and then dropped to 83% after 104 weeks.
During weeks 53-104 on treatment the rates of adverse events, serious adverse events, serious infections, adverse events resulting in treatment discontinuation, enteric infections, and malignancies were all low and similar to the event rates seen among the patients randomized to placebo in the GEMINI 1 study. The same pattern of low event rates similar to the placebo patients also occurred for episodes of nasopharyngitis, upper respiratory tract infections, Clostridium difficile infections, and tuberculosis cases.
The results also showed better rates of long-term remission and response in the patients who had not previously failed treatment with an anti-TNF drug compared with those who had. Asked what might explain this, Dr. Feagan replied “we know that patients who fail prior drugs are always harder to treat.”
A very similar pattern occurred among the patients with Crohn’s disease who remained on vedolizumab for an additional 52 weeks following completion of a first year of treatment in the GEMINI 2 trial [the Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Crohn’s Disease], the pivotal, phase III study that led to the Crohn’s disease indication for vedolizumab (N. Engl. J. Med. 2013;369:711-21). Among 295 GEMINI 2 completer patients who remained on vedolizumab the rate of complete remissions was 57% at entry into the long-term study after 52 weeks on treatment, 64% after 80 weeks on treatment, and 61% after 104 weeks.The overall response rate was 81% at 52 weeks, 78% after 80 weeks, and 74% at 104 week, Dr. Rutgeerts reported. However, he noted that the study design allowed patients who experienced a flare to receive conventional rescue medications and still be counted a responder or in remission, which increased the number of patients in both of these two groups. “Patients did not need to be a responder or in remission at every time point,” he noted.
Once again, the rates of adverse events, serious adverse events, adverse events resulting in drug discontinuation, infections, serious infections, nasopharyngitis, and upper respiratory infection were all similar among patients on long-term vedolizumab compared with control patients with Crohn’s disease, Dr. Rutgeerts said.
The results suggest that with vedolizumab treatment of inflammatory bowel disease “once you achieve an effect it is long-lasting,” Dr. Rutgeerts said in an interview. But he cautioned that the long-lasting efficacy was achieved with treatment every 4 weeks. While this approach was safe, it would also be expensive in routine practice, he noted. “The safety looks good, but the cost would be very high.”
“A key concept of vedolizumab is that it builds efficacy over time,” commented Dr. Silvio Danese during a talk at the meeting. “Vedolizumab is not the fastest runner, but [treating inflammatory bowel disease] is a marathon, and the important thing is getting to the finish,” said Dr. Danese, head of the inflammatory bowel disease unit at the Humanitas Clinic and Research Center in Milan.
Dr. Danese also said that vedolizumab has a safety advantage over anti-TNF drugs when treating ulcerative colitis, although vedolizumab’s efficacy for treating steroid-refractory, fulminant ulcertative colitis remains untested. And he agreed that vedolizumab’s role as a go-to agent for inducing remission in active Crohn’s disease seems questionable.
Two other reports at the meeting further fleshed out vedolizumab’s performance in the GEMINI trials.
One analysis focused on 34 ulcerative colitis patients and 57 Crohn’s disease patients who responded to vedolizumab induction treatment but then lost their response when they subsequently received vedolizumab once every 8 weeks. These patients then switched to a regimen in which they received the drug every 4 weeks, and this resulted in significant reductions in disease activity among some of the ulcerative colitis and Crohn’s disease patients, reported Dr. Séverine Vermeire, a gastroenterologist and professor of medicine at Catholic University in Leuven.
She estimated that roughly a third of patients in both disease categories who lost response when put on the drug once every 8 weeks regained their complete response when their dosing frequency increased to once every 4 weeks.
The findings “suggest that dosing every 4 weeks may be beneficial for certain patients, with no apparent change in safety. These data provide insight into the potential value of dosing every 4 weeks, and in routine practice we will have patients who will lose response when they receive the drug every 8 weeks,” Dr. Vermeire said. “We should try to identify these patients early,” she said, and “we need to investigate why some patients lose their vedolizumab response.” The labeling for vedolizumab calls for treatment once every 8 weeks for maintenance.
Another analysis focused on the total of 1,443 inflammatory bowel disease patients who received vedolizumab for both induction and maintenance in the two GEMINI studies. This safety analysis examined the incidence of total infections and serious infections among patients who started on vedolizumab while on treatment with a corticosteroid, an immunomodulating drug, both of these agents, or neither of these agents.
The analysis showed similar rates of both total infections and serious infections in all four subgroups, suggesting no interaction between vedsolizumab and other immuno-active drugs in terms of vulnerability to infection, said Dr. Jean-Frédréic Colombel, professor of medicine and director of the inflammatory bowel disease center at Mount Sinai Medical Center in New York.
The low rate of serious infections, which occurred at 0.04-0.06 infections/person-year of follow-up was “reassuring,” said Dr. Colombel, but these infections were also so rare that it limited interpretation of the findings. He also noted that the analysis only focused on concomitant drugs at the time patients began vedolizumab treatment and did not take into account subsequent medication changes.
The GEMINI 1 and 2 trials were sponsored by Takeda, the company that markets vedolizumab (Entyvio). Dr. Feagan has been a consultant to Takeda, AbbVie, Merck, and UCB. Dr. Rutgeerts has been a consultant to Takeda, AbbVie, Janssen, Merch, and UCB. Dr. van der Woude has been an advisor to Dr. Falk, Abbvie, Janssen, Johnson&Johnson, and Cosmo. Dr. Danese has been a consultant to Takeda and to several other companies. Dr. Vermeire has been a consultant to Takeda and to several other companies. Dr. Colombel has been a consultant to Takeda and to several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – Vedolizumab, a second-line biologic for treating patients who have ulcerative colitis or Crohn’s disease and don’t respond to an anti-tumor necrosis factor drug, is gaining traction with experts who have used the drug investigationally for several years and consider vedolizumab to be their first-line biologic for ulcerative colitis. But they agree that for Crohn’s disease the available data support using vedolizumab as a second-line agent.
“I think vedolizumab [Entyvio] is a first-line biologic for ulcerative colitis. Full stop,” said Dr. Brian G. Feagan during a talk at the United European Gastroenterology Global Congress. He cited his 12-year experience using vedolizumab, which has compiled a strong record of efficacy as well as safety for ulcerative colitis.
“It’s the promise of a reduced risk of systemic adverse events, especially secondary infections,” by using vedolizumab instead of a drug that blocks tumor necrosis factor (TNF), said Dr. Feagan in an interview.
“For Crohn’s disease, vedolizumab seems to have a slower onset of action, so for sicker Crohn’s patients you may want to choose a TNF blocker,” said Dr. Feagan, a gastroenterologist and professor of medicine at the University of Western Ontario in London, Ont. “For Crohn’s disease you could use vedolizumab first in some patients and an anti-TNF first line in other patients.”
Another gastroenterologist experienced in using vedolizumab to treat inflammatory bowel diseases largely agreed. “Vedolizumab is a first-line biologic for ulcerative colitis, For Crohn’s disease, the anti-TNF drugs are still the way to go,” said Dr. Paul Rutgeerts, a gastroenterologist and professor of medicine at Catholic University in Leuven, Belgium.
Dr. Feagan and Dr. Rutgeerts as well as others cite a fundamental difference in the way vedolizumab mitigates autoimmunity compared with TNF blocking drugs as the likely explanation for why vedolizumab seems to work much better for ulcerative colitis than it does for Crohn’s disease.
As spelled out last year in an editorial by Dr. Fabio Cominelli (N. Engl. J. Med. 2013;369:775-6), vedolizumab specifically blocks the integrin that directs leukocytes to the gut musoca, and this limited, gut-specific action may explain why the drug has such a favorable adverse effect profile as well as why it is less effective at inducing remissions in Crohn’s disease, which can hit any site along the entire gastrointestinal tract and cause transmural fistulas and multi-organ involvement. In contrast, ulcerative colitis is limited to the superficial mucosa of the large bowel.
“With ulcerative colitis it is only the mucosa. Crohn’s disease is more of a transmural disorder that involves the entire wall of the gut so you have more need for systemic action, which is better delivered by anti-TNFs” than by vedolizumab, Dr. Rutgeerts said in an interview.
Perhaps vedolizumab’s only major drawback as first-line biologic treatment for ulcerative colitis and even for some Crohn’s disease patients is its high cost, especially at a time when the price for the anti-TNF drug infliximab has begun to fall following introduction of biosimilar infliximab in Europe and its expected appearance soon in the United States.
“The cost [of vedolizumab] is very high,” especially when administered every 4 weeks, which seems to be the dosage many patients need to maintain long-term responses and remissions, Dr. Rutgeerts said.
“Now we have biosimilar infliximab, which is cheaper than vedolizumab” and hence more attractive, at least for cost, noted Dr. C. Janneke van der Woude, head of the inflammatory bowel diseases unit at Erasmus University in Rotterdam, The Netherlands. She also noted that many patients prefer subcutaneous drug treatment with the anti-TNF agent adalimumab over intravenous treatments, which is the route for vedolizumab.
Two-year data show durable efficacy, safety
Vedolizumab demonstrated its ability to safely maintain remission in responsive patients with inflammatory bowel disease in results from long-term treatment and follow-up of patients enrolled in the pivotal phase III trials that supplied the data that led to vedolizumab’s marketing approval earlier this year in both the United States and in Europe.
Dr. Feagan presented outcome results after 80 and 104 weeks of vedolizumab treatment of 278 patients with ulcerative colitis who had completed a full year of treatment during the GEMINI 1 trial [Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Ulcerative Colitis] (N. Engl. J. Med. 2013;369:699-710). He reported that the percentage of patients in clinical remission grew from 66% after 52 weeks on treatment (the time of entry into the long-term phase of the study), to 77% after 80 weeks, which then dropped to 73% after 104 weeks. Patients with a clinical response increased from 78% after 52 weeks to 88% after 80 weeks, and then dropped to 83% after 104 weeks.
During weeks 53-104 on treatment the rates of adverse events, serious adverse events, serious infections, adverse events resulting in treatment discontinuation, enteric infections, and malignancies were all low and similar to the event rates seen among the patients randomized to placebo in the GEMINI 1 study. The same pattern of low event rates similar to the placebo patients also occurred for episodes of nasopharyngitis, upper respiratory tract infections, Clostridium difficile infections, and tuberculosis cases.
The results also showed better rates of long-term remission and response in the patients who had not previously failed treatment with an anti-TNF drug compared with those who had. Asked what might explain this, Dr. Feagan replied “we know that patients who fail prior drugs are always harder to treat.”
A very similar pattern occurred among the patients with Crohn’s disease who remained on vedolizumab for an additional 52 weeks following completion of a first year of treatment in the GEMINI 2 trial [the Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Crohn’s Disease], the pivotal, phase III study that led to the Crohn’s disease indication for vedolizumab (N. Engl. J. Med. 2013;369:711-21). Among 295 GEMINI 2 completer patients who remained on vedolizumab the rate of complete remissions was 57% at entry into the long-term study after 52 weeks on treatment, 64% after 80 weeks on treatment, and 61% after 104 weeks.The overall response rate was 81% at 52 weeks, 78% after 80 weeks, and 74% at 104 week, Dr. Rutgeerts reported. However, he noted that the study design allowed patients who experienced a flare to receive conventional rescue medications and still be counted a responder or in remission, which increased the number of patients in both of these two groups. “Patients did not need to be a responder or in remission at every time point,” he noted.
Once again, the rates of adverse events, serious adverse events, adverse events resulting in drug discontinuation, infections, serious infections, nasopharyngitis, and upper respiratory infection were all similar among patients on long-term vedolizumab compared with control patients with Crohn’s disease, Dr. Rutgeerts said.
The results suggest that with vedolizumab treatment of inflammatory bowel disease “once you achieve an effect it is long-lasting,” Dr. Rutgeerts said in an interview. But he cautioned that the long-lasting efficacy was achieved with treatment every 4 weeks. While this approach was safe, it would also be expensive in routine practice, he noted. “The safety looks good, but the cost would be very high.”
“A key concept of vedolizumab is that it builds efficacy over time,” commented Dr. Silvio Danese during a talk at the meeting. “Vedolizumab is not the fastest runner, but [treating inflammatory bowel disease] is a marathon, and the important thing is getting to the finish,” said Dr. Danese, head of the inflammatory bowel disease unit at the Humanitas Clinic and Research Center in Milan.
Dr. Danese also said that vedolizumab has a safety advantage over anti-TNF drugs when treating ulcerative colitis, although vedolizumab’s efficacy for treating steroid-refractory, fulminant ulcertative colitis remains untested. And he agreed that vedolizumab’s role as a go-to agent for inducing remission in active Crohn’s disease seems questionable.
Two other reports at the meeting further fleshed out vedolizumab’s performance in the GEMINI trials.
One analysis focused on 34 ulcerative colitis patients and 57 Crohn’s disease patients who responded to vedolizumab induction treatment but then lost their response when they subsequently received vedolizumab once every 8 weeks. These patients then switched to a regimen in which they received the drug every 4 weeks, and this resulted in significant reductions in disease activity among some of the ulcerative colitis and Crohn’s disease patients, reported Dr. Séverine Vermeire, a gastroenterologist and professor of medicine at Catholic University in Leuven.
She estimated that roughly a third of patients in both disease categories who lost response when put on the drug once every 8 weeks regained their complete response when their dosing frequency increased to once every 4 weeks.
The findings “suggest that dosing every 4 weeks may be beneficial for certain patients, with no apparent change in safety. These data provide insight into the potential value of dosing every 4 weeks, and in routine practice we will have patients who will lose response when they receive the drug every 8 weeks,” Dr. Vermeire said. “We should try to identify these patients early,” she said, and “we need to investigate why some patients lose their vedolizumab response.” The labeling for vedolizumab calls for treatment once every 8 weeks for maintenance.
Another analysis focused on the total of 1,443 inflammatory bowel disease patients who received vedolizumab for both induction and maintenance in the two GEMINI studies. This safety analysis examined the incidence of total infections and serious infections among patients who started on vedolizumab while on treatment with a corticosteroid, an immunomodulating drug, both of these agents, or neither of these agents.
The analysis showed similar rates of both total infections and serious infections in all four subgroups, suggesting no interaction between vedsolizumab and other immuno-active drugs in terms of vulnerability to infection, said Dr. Jean-Frédréic Colombel, professor of medicine and director of the inflammatory bowel disease center at Mount Sinai Medical Center in New York.
The low rate of serious infections, which occurred at 0.04-0.06 infections/person-year of follow-up was “reassuring,” said Dr. Colombel, but these infections were also so rare that it limited interpretation of the findings. He also noted that the analysis only focused on concomitant drugs at the time patients began vedolizumab treatment and did not take into account subsequent medication changes.
The GEMINI 1 and 2 trials were sponsored by Takeda, the company that markets vedolizumab (Entyvio). Dr. Feagan has been a consultant to Takeda, AbbVie, Merck, and UCB. Dr. Rutgeerts has been a consultant to Takeda, AbbVie, Janssen, Merch, and UCB. Dr. van der Woude has been an advisor to Dr. Falk, Abbvie, Janssen, Johnson&Johnson, and Cosmo. Dr. Danese has been a consultant to Takeda and to several other companies. Dr. Vermeire has been a consultant to Takeda and to several other companies. Dr. Colombel has been a consultant to Takeda and to several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM UEG WEEK VIENNA 2014
