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Oral drug cut viral respiratory tract infections in elderly
WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.
At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.
During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.
RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.
The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.
The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.
The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.
The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.
WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.
At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.
During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.
RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.
The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.
The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.
The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.
The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.
WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.
At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.
During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.
RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.
The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.
The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.
The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.
The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.
REPORTING FROM IDWEEK 2019
Massachusetts tops state vaccination rankings
according to a new analysis from personal finance website WalletHub.
The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.
The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.
Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.
“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”
according to a new analysis from personal finance website WalletHub.
The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.
The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.
Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.
“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”
according to a new analysis from personal finance website WalletHub.
The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.
The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.
Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.
“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”
IHS Pediatrician Convicted on Sexual Abuse Counts
Stanley Patrick Weber, a former Indian Health Service (IHS) pediatrician, was convicted September 27 on 8 counts of sexual abuse of 4 Native American boys under his care at the Pine Ridge Indian Reservation, Oglala Lakota County, South Dakota.
Weber was an employee of the IHS from 1986 until he resigned in 2016. During that time, although suspicions were rampant that he was abusing young patients, he was moved from one reservation to another. An investigation by The Wall Street Journal and PBS/Frontline found officials in the IHS chain of command “ignored warning signs” and tried to silence whistleblowers.
Weber also was convicted last year and served time for abusing 2 boys at another government hospital in Montana before he arrived at Pine Ridge.
The Pine Ridge Reservation is home to some of the poorest communities in the US, with a dropout rate of > 70%, and a teen suicide rate 150% higher than America’s as a whole. Many of the youths testifying in the case described difficult childhoods, according to the Frontline program. In addition to assaulting them during health care visits, Weber lured them to his home with offers of alcohol and cash.
A White House task force was created to address the agency’s failures. In a statement, Rear Adm Michael Weahkee, IHS principal deputy director, said the IHS is “doing all we can throughout our agency to strengthen our protection for patients.” Steps taken include reinforcing with staff the prohibitions against inappropriate contact with children, reminding staff of the protections for whistleblowers, and hiring Integritas Creative Solutions to conduct a medical quality assurance review to examine whether laws, policies and procedures have been followed with regard to protecting patients from sexual abuse. The review complements work done by the Presidential Task Force on Protecting Native American Children in the Indian Health Service System and a separate review by the HHS Office of the Inspector General.
The IHS also is providing professional counseling for victims. Services do not have to be at an IHS facility or with an IHS provider. A confidential hot line has been established at 301-443-0658.
Weahkee calls the verdict “a long-awaited victory.” But, he adds, “we know that it will not completely heal the wounds inflicted on Dr. Weber’s victims.”
Stanley Patrick Weber, a former Indian Health Service (IHS) pediatrician, was convicted September 27 on 8 counts of sexual abuse of 4 Native American boys under his care at the Pine Ridge Indian Reservation, Oglala Lakota County, South Dakota.
Weber was an employee of the IHS from 1986 until he resigned in 2016. During that time, although suspicions were rampant that he was abusing young patients, he was moved from one reservation to another. An investigation by The Wall Street Journal and PBS/Frontline found officials in the IHS chain of command “ignored warning signs” and tried to silence whistleblowers.
Weber also was convicted last year and served time for abusing 2 boys at another government hospital in Montana before he arrived at Pine Ridge.
The Pine Ridge Reservation is home to some of the poorest communities in the US, with a dropout rate of > 70%, and a teen suicide rate 150% higher than America’s as a whole. Many of the youths testifying in the case described difficult childhoods, according to the Frontline program. In addition to assaulting them during health care visits, Weber lured them to his home with offers of alcohol and cash.
A White House task force was created to address the agency’s failures. In a statement, Rear Adm Michael Weahkee, IHS principal deputy director, said the IHS is “doing all we can throughout our agency to strengthen our protection for patients.” Steps taken include reinforcing with staff the prohibitions against inappropriate contact with children, reminding staff of the protections for whistleblowers, and hiring Integritas Creative Solutions to conduct a medical quality assurance review to examine whether laws, policies and procedures have been followed with regard to protecting patients from sexual abuse. The review complements work done by the Presidential Task Force on Protecting Native American Children in the Indian Health Service System and a separate review by the HHS Office of the Inspector General.
The IHS also is providing professional counseling for victims. Services do not have to be at an IHS facility or with an IHS provider. A confidential hot line has been established at 301-443-0658.
Weahkee calls the verdict “a long-awaited victory.” But, he adds, “we know that it will not completely heal the wounds inflicted on Dr. Weber’s victims.”
Stanley Patrick Weber, a former Indian Health Service (IHS) pediatrician, was convicted September 27 on 8 counts of sexual abuse of 4 Native American boys under his care at the Pine Ridge Indian Reservation, Oglala Lakota County, South Dakota.
Weber was an employee of the IHS from 1986 until he resigned in 2016. During that time, although suspicions were rampant that he was abusing young patients, he was moved from one reservation to another. An investigation by The Wall Street Journal and PBS/Frontline found officials in the IHS chain of command “ignored warning signs” and tried to silence whistleblowers.
Weber also was convicted last year and served time for abusing 2 boys at another government hospital in Montana before he arrived at Pine Ridge.
The Pine Ridge Reservation is home to some of the poorest communities in the US, with a dropout rate of > 70%, and a teen suicide rate 150% higher than America’s as a whole. Many of the youths testifying in the case described difficult childhoods, according to the Frontline program. In addition to assaulting them during health care visits, Weber lured them to his home with offers of alcohol and cash.
A White House task force was created to address the agency’s failures. In a statement, Rear Adm Michael Weahkee, IHS principal deputy director, said the IHS is “doing all we can throughout our agency to strengthen our protection for patients.” Steps taken include reinforcing with staff the prohibitions against inappropriate contact with children, reminding staff of the protections for whistleblowers, and hiring Integritas Creative Solutions to conduct a medical quality assurance review to examine whether laws, policies and procedures have been followed with regard to protecting patients from sexual abuse. The review complements work done by the Presidential Task Force on Protecting Native American Children in the Indian Health Service System and a separate review by the HHS Office of the Inspector General.
The IHS also is providing professional counseling for victims. Services do not have to be at an IHS facility or with an IHS provider. A confidential hot line has been established at 301-443-0658.
Weahkee calls the verdict “a long-awaited victory.” But, he adds, “we know that it will not completely heal the wounds inflicted on Dr. Weber’s victims.”
Vaping-associated lung injury cases exceed 1,000
More than 1,000 cases of vaping-associated lung injury have been reported in 48 states and the U.S. Virgin Islands, according to a telebriefing by the Centers for Disease Control and Prevention.
As of Oct. 1, there have been 1,080 confirmed and probable cases of lung injury associated with the use of e-cigarettes, or vaping, said Anne Schuchat, MD, principal deputy director of the CDC. The latest figures were also reported in a statement issued by the CDC.
Dr. Schuchat said 18 related deaths in 15 states have been confirmed, and additional deaths are under investigation.
“As we have continued to get data for additional cases, the trends we reported last week persist,” Dr. Schuchat said (MMWR. 2019 Sep 27;68[39];860-4).
“Most patients reported a history of using THC [tetrahydrocannabinol]-containing products, and most patients are male and young people.” Of the 1,080 cases identified, approximately 70% are male, roughly 80% are younger than 35 years of age, and 37% are under 21 years of age. The patients’ median age is 23 years (range, 13-75 years). Among patients who have died, the median age is 50 years (range, 27-71 years).
The CDC now has information from 578 patients on the substances used in vaping products in the 90 days before symptom onset. About 78% of these patients reported using THC-containing products, and 37% reported exclusive use of THC-containing products. Roughly 58% of patients reported using nicotine-containing products, and 17% reported exclusive use of nicotine-containing products.
“I wish we had more answers regarding the specific harmful products or components that are causing these illnesses,” Dr. Schuchat said. She noted that THC-containing products appear to be the most commonly used, but these products don’t appear to be the only culprit. Additionally, in a report released recently in the New England Journal of Medicine (2019 Sep 9. doi: 10.1056/NEJMoa1911614), THC-containing products bought “off the street” were commonly used by patients with lung injuries. However, the CDC can’t say for certain if it’s safer for consumers to buy THC-containing products from a licensed dispensary.
The CDC has deployed staff to several states to help investigate the lung injuries, reached out to the clinical community to increase awareness of the injuries, and worked with clinicians and medical examiners to review assessments of patients who have developed these injuries, including those who have died. The CDC has also convened clinical professional societies to “help strengthen the detection, reporting, and management of cases,” Dr. Schuchat said.
In addition, the CDC has joined with the Food and Drug Administration and other public health partners to develop a laboratory plan for “continued testing of products, aerosol testing of substances produced by the products, and clinical pathology lung specimens from patients,” Dr. Schuchat said.
The FDA is also working to gather more information about vaping-associated lung injuries. The FDA is trying to obtain “critical details” about the specific products or substances that may be involved, said Judy McMeekin, PharmD, deputy associate commissioner for regulatory affairs at the FDA.
“There does not currently appear to be one product or substance involved in all of the cases,” Dr. McMeekin said. “We are leaving no stone unturned and following all potential leads regarding any particular product, constituent, or compound that may be at issue.”
The FDA has collected more than 440 samples of vaping devices and products from 18 states. The agency is still analyzing these samples, but a preliminary analysis has shown that some products contain THC concentrations ranging from 14% to 76%, and some products contain a combination of THC and vitamin E acetate ranging from 31% to 88%.
For information about the collection of vaping products for possible testing by the FDA, email FDAVapingSampleInquiries@fda.hhs.gov. For information about collection and submission of clinical specimens for possible testing by the CDC, see the Healthcare Provider webpage.
Clinicians and health officials who have questions about this outbreak can email LungDiseaseOutbreak@cdc.gov. All others with questions about this outbreak can contact CDC-INFO at 800-232-4636 or submit information at the Contact CDC-INFO page.
More than 1,000 cases of vaping-associated lung injury have been reported in 48 states and the U.S. Virgin Islands, according to a telebriefing by the Centers for Disease Control and Prevention.
As of Oct. 1, there have been 1,080 confirmed and probable cases of lung injury associated with the use of e-cigarettes, or vaping, said Anne Schuchat, MD, principal deputy director of the CDC. The latest figures were also reported in a statement issued by the CDC.
Dr. Schuchat said 18 related deaths in 15 states have been confirmed, and additional deaths are under investigation.
“As we have continued to get data for additional cases, the trends we reported last week persist,” Dr. Schuchat said (MMWR. 2019 Sep 27;68[39];860-4).
“Most patients reported a history of using THC [tetrahydrocannabinol]-containing products, and most patients are male and young people.” Of the 1,080 cases identified, approximately 70% are male, roughly 80% are younger than 35 years of age, and 37% are under 21 years of age. The patients’ median age is 23 years (range, 13-75 years). Among patients who have died, the median age is 50 years (range, 27-71 years).
The CDC now has information from 578 patients on the substances used in vaping products in the 90 days before symptom onset. About 78% of these patients reported using THC-containing products, and 37% reported exclusive use of THC-containing products. Roughly 58% of patients reported using nicotine-containing products, and 17% reported exclusive use of nicotine-containing products.
“I wish we had more answers regarding the specific harmful products or components that are causing these illnesses,” Dr. Schuchat said. She noted that THC-containing products appear to be the most commonly used, but these products don’t appear to be the only culprit. Additionally, in a report released recently in the New England Journal of Medicine (2019 Sep 9. doi: 10.1056/NEJMoa1911614), THC-containing products bought “off the street” were commonly used by patients with lung injuries. However, the CDC can’t say for certain if it’s safer for consumers to buy THC-containing products from a licensed dispensary.
The CDC has deployed staff to several states to help investigate the lung injuries, reached out to the clinical community to increase awareness of the injuries, and worked with clinicians and medical examiners to review assessments of patients who have developed these injuries, including those who have died. The CDC has also convened clinical professional societies to “help strengthen the detection, reporting, and management of cases,” Dr. Schuchat said.
In addition, the CDC has joined with the Food and Drug Administration and other public health partners to develop a laboratory plan for “continued testing of products, aerosol testing of substances produced by the products, and clinical pathology lung specimens from patients,” Dr. Schuchat said.
The FDA is also working to gather more information about vaping-associated lung injuries. The FDA is trying to obtain “critical details” about the specific products or substances that may be involved, said Judy McMeekin, PharmD, deputy associate commissioner for regulatory affairs at the FDA.
“There does not currently appear to be one product or substance involved in all of the cases,” Dr. McMeekin said. “We are leaving no stone unturned and following all potential leads regarding any particular product, constituent, or compound that may be at issue.”
The FDA has collected more than 440 samples of vaping devices and products from 18 states. The agency is still analyzing these samples, but a preliminary analysis has shown that some products contain THC concentrations ranging from 14% to 76%, and some products contain a combination of THC and vitamin E acetate ranging from 31% to 88%.
For information about the collection of vaping products for possible testing by the FDA, email FDAVapingSampleInquiries@fda.hhs.gov. For information about collection and submission of clinical specimens for possible testing by the CDC, see the Healthcare Provider webpage.
Clinicians and health officials who have questions about this outbreak can email LungDiseaseOutbreak@cdc.gov. All others with questions about this outbreak can contact CDC-INFO at 800-232-4636 or submit information at the Contact CDC-INFO page.
More than 1,000 cases of vaping-associated lung injury have been reported in 48 states and the U.S. Virgin Islands, according to a telebriefing by the Centers for Disease Control and Prevention.
As of Oct. 1, there have been 1,080 confirmed and probable cases of lung injury associated with the use of e-cigarettes, or vaping, said Anne Schuchat, MD, principal deputy director of the CDC. The latest figures were also reported in a statement issued by the CDC.
Dr. Schuchat said 18 related deaths in 15 states have been confirmed, and additional deaths are under investigation.
“As we have continued to get data for additional cases, the trends we reported last week persist,” Dr. Schuchat said (MMWR. 2019 Sep 27;68[39];860-4).
“Most patients reported a history of using THC [tetrahydrocannabinol]-containing products, and most patients are male and young people.” Of the 1,080 cases identified, approximately 70% are male, roughly 80% are younger than 35 years of age, and 37% are under 21 years of age. The patients’ median age is 23 years (range, 13-75 years). Among patients who have died, the median age is 50 years (range, 27-71 years).
The CDC now has information from 578 patients on the substances used in vaping products in the 90 days before symptom onset. About 78% of these patients reported using THC-containing products, and 37% reported exclusive use of THC-containing products. Roughly 58% of patients reported using nicotine-containing products, and 17% reported exclusive use of nicotine-containing products.
“I wish we had more answers regarding the specific harmful products or components that are causing these illnesses,” Dr. Schuchat said. She noted that THC-containing products appear to be the most commonly used, but these products don’t appear to be the only culprit. Additionally, in a report released recently in the New England Journal of Medicine (2019 Sep 9. doi: 10.1056/NEJMoa1911614), THC-containing products bought “off the street” were commonly used by patients with lung injuries. However, the CDC can’t say for certain if it’s safer for consumers to buy THC-containing products from a licensed dispensary.
The CDC has deployed staff to several states to help investigate the lung injuries, reached out to the clinical community to increase awareness of the injuries, and worked with clinicians and medical examiners to review assessments of patients who have developed these injuries, including those who have died. The CDC has also convened clinical professional societies to “help strengthen the detection, reporting, and management of cases,” Dr. Schuchat said.
In addition, the CDC has joined with the Food and Drug Administration and other public health partners to develop a laboratory plan for “continued testing of products, aerosol testing of substances produced by the products, and clinical pathology lung specimens from patients,” Dr. Schuchat said.
The FDA is also working to gather more information about vaping-associated lung injuries. The FDA is trying to obtain “critical details” about the specific products or substances that may be involved, said Judy McMeekin, PharmD, deputy associate commissioner for regulatory affairs at the FDA.
“There does not currently appear to be one product or substance involved in all of the cases,” Dr. McMeekin said. “We are leaving no stone unturned and following all potential leads regarding any particular product, constituent, or compound that may be at issue.”
The FDA has collected more than 440 samples of vaping devices and products from 18 states. The agency is still analyzing these samples, but a preliminary analysis has shown that some products contain THC concentrations ranging from 14% to 76%, and some products contain a combination of THC and vitamin E acetate ranging from 31% to 88%.
For information about the collection of vaping products for possible testing by the FDA, email FDAVapingSampleInquiries@fda.hhs.gov. For information about collection and submission of clinical specimens for possible testing by the CDC, see the Healthcare Provider webpage.
Clinicians and health officials who have questions about this outbreak can email LungDiseaseOutbreak@cdc.gov. All others with questions about this outbreak can contact CDC-INFO at 800-232-4636 or submit information at the Contact CDC-INFO page.
One-third of patients with severe asthma are overusing corticosteroids
MADRID – if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.
“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.
In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.
Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.
In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.
On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,
When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.
Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.
“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.
The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.
“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.
In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.
“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”
Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.
Dr. Eger reports no potential conflicts of interest.
MADRID – if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.
“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.
In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.
Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.
In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.
On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,
When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.
Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.
“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.
The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.
“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.
In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.
“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”
Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.
Dr. Eger reports no potential conflicts of interest.
MADRID – if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.
“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.
In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.
Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.
In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.
On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,
When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.
Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.
“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.
The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.
“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.
In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.
“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”
Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.
Dr. Eger reports no potential conflicts of interest.
REPORTING FROM ERS 2019
Six factors predicted benefit from asthma triple therapy
MADRID – Two newly published but previously reported phase 3 trials associated triple therapy in a single inhaler with a 23% reduction (P = .008) in asthma exacerbations relative to a two-drug inhaler, but fresh data from a prespecified analysis presented at the annual congress of the European Respiratory Society has identified those patients most likely to benefit.
“Six easily identifiable factors appear to be associated with the most prominent response to treatment and may help in the treatment step-up decision at the point of care,” reported Dave Singh, MD, professor in the division of infection, immunity, and respiratory medicine, University of Manchester (England).
The primary results of these trials were presented several months ago at the 2019 American Thoracic Society (ATS) meeting, but the full data were published on the day that Dr. Singh spoke at the ERS.
To identify predictors of response, the pooled analysis of TRIMARIN and TRIGGER was prespecified. Both of these trials, which were similarly designed, compared a single inhaler of inhaled corticosteroids (ICS), long-acting beta agonist (LABA), and long-acting muscarinic antagonist (LAMA) to a single ICS/LABA inhaler.
On the basis of risk for severe exacerbations, greater protection from triple therapy relative to a conventional ICS/LABA inhaler was identified for those with a high degree of reversibility (defined as greater than 400 mL) relative to those with a lower degree (RR, 0.729; P = .024), those with a body mass index less than 25 kg/m2 relative to a higher BMI (RR, 0.570; P = .005), those with only one exacerbation in the previous 12 months relative to those with more (RR, 0.731; P = .009), never-smokers relative to those with smoking history (RR, 0.764; P = .013), those younger than age 65 years relative to older (RR, 0.770; P = .17), and males relative to females (RR, 0.651; P = .009).
“This gives us six factors to consider when you are thinking about stepping up to triple therapy and are trying to determine which patients would benefit the most,” Dr. Singh said.
Both the TRIMARIN and the TRIGGER trials were double blind and placebo controlled. In both, the experimental arm was a single inhaler triple therapy of the ICS beclomethasone, the LABA formoterol, and the LAMA glycopyrronium. The control arm was a single inhaler combination of beclomethasone and formoterol. All inhalers were used twice daily.
TRIMARIN, with 171 participating sites in 16 countries, randomized 1,155 patients to the triple-drug inhaler with a moderate dose of ICS (100 mcg) or to the ICS/LABA inhaler. In TRIGGER, with 221 sites in 17 countries, 1,437 patients were randomized to one of three arms. Both the triple-drug inhaler arm and the ICS/LABA arm contained a higher dose of ICS (200 mcg) than in TRIMARIN. In an open-label third arm, patients also received the higher dose of ICS plus LABA and a second inhaler with tiotropium. The formoterol dose in all arms of both studies was 6 mcg.
As reported at the ATS and now published in the Lancet, the reduction in exacerbations on single inhaler triple therapy relative to ICS/LABA was significant when the data were pooled (even though the reduction in the TRIGGER study fell short of statistical significance). The median improvement in lung function for single inhaler triple therapy relative to ICS/LABA was significant in both TRIMARIN (57 mL; P = .008) and TRIGGER (73 mL; P = .0025).
In discussing the new pooled analysis of response predictors in TRIMARIN/TRIGGER, the ERS-invited discussant, Celeste M. Porsbjerg, MD, Bispebjerg Hospital, Copenhagen, expressed particular interest in reversibility. A positive reversibility test to salbutamol was an entry criterion for both trials, but Dr. Porsbjerg pointed out that a greater response in those with the highest reversibility suggests these patients have a phenotype in which bronchodilation is a more important driver of disease than is inflammation.
While conceding that this was possible, Dr. Singh cautioned that he considers these predictors of response to be “exploratory.” He believes that the TRIMARIN/TRIGGER studies were not designed to tease out the relative importance of mechanisms of asthma in response to the assigned therapies. However, he believes the response predictor analysis is a step in this direction, which might be valuable for better individualizing therapy.
The studies were funded by Chiesi Farmaceutici. Dr. Singh reports no potential conflicts of interest.
Virchow JC et al. Lancet. 2019 Sep 30. doi. org/10.1016/S0140-6736(19)32215-9.
MADRID – Two newly published but previously reported phase 3 trials associated triple therapy in a single inhaler with a 23% reduction (P = .008) in asthma exacerbations relative to a two-drug inhaler, but fresh data from a prespecified analysis presented at the annual congress of the European Respiratory Society has identified those patients most likely to benefit.
“Six easily identifiable factors appear to be associated with the most prominent response to treatment and may help in the treatment step-up decision at the point of care,” reported Dave Singh, MD, professor in the division of infection, immunity, and respiratory medicine, University of Manchester (England).
The primary results of these trials were presented several months ago at the 2019 American Thoracic Society (ATS) meeting, but the full data were published on the day that Dr. Singh spoke at the ERS.
To identify predictors of response, the pooled analysis of TRIMARIN and TRIGGER was prespecified. Both of these trials, which were similarly designed, compared a single inhaler of inhaled corticosteroids (ICS), long-acting beta agonist (LABA), and long-acting muscarinic antagonist (LAMA) to a single ICS/LABA inhaler.
On the basis of risk for severe exacerbations, greater protection from triple therapy relative to a conventional ICS/LABA inhaler was identified for those with a high degree of reversibility (defined as greater than 400 mL) relative to those with a lower degree (RR, 0.729; P = .024), those with a body mass index less than 25 kg/m2 relative to a higher BMI (RR, 0.570; P = .005), those with only one exacerbation in the previous 12 months relative to those with more (RR, 0.731; P = .009), never-smokers relative to those with smoking history (RR, 0.764; P = .013), those younger than age 65 years relative to older (RR, 0.770; P = .17), and males relative to females (RR, 0.651; P = .009).
“This gives us six factors to consider when you are thinking about stepping up to triple therapy and are trying to determine which patients would benefit the most,” Dr. Singh said.
Both the TRIMARIN and the TRIGGER trials were double blind and placebo controlled. In both, the experimental arm was a single inhaler triple therapy of the ICS beclomethasone, the LABA formoterol, and the LAMA glycopyrronium. The control arm was a single inhaler combination of beclomethasone and formoterol. All inhalers were used twice daily.
TRIMARIN, with 171 participating sites in 16 countries, randomized 1,155 patients to the triple-drug inhaler with a moderate dose of ICS (100 mcg) or to the ICS/LABA inhaler. In TRIGGER, with 221 sites in 17 countries, 1,437 patients were randomized to one of three arms. Both the triple-drug inhaler arm and the ICS/LABA arm contained a higher dose of ICS (200 mcg) than in TRIMARIN. In an open-label third arm, patients also received the higher dose of ICS plus LABA and a second inhaler with tiotropium. The formoterol dose in all arms of both studies was 6 mcg.
As reported at the ATS and now published in the Lancet, the reduction in exacerbations on single inhaler triple therapy relative to ICS/LABA was significant when the data were pooled (even though the reduction in the TRIGGER study fell short of statistical significance). The median improvement in lung function for single inhaler triple therapy relative to ICS/LABA was significant in both TRIMARIN (57 mL; P = .008) and TRIGGER (73 mL; P = .0025).
In discussing the new pooled analysis of response predictors in TRIMARIN/TRIGGER, the ERS-invited discussant, Celeste M. Porsbjerg, MD, Bispebjerg Hospital, Copenhagen, expressed particular interest in reversibility. A positive reversibility test to salbutamol was an entry criterion for both trials, but Dr. Porsbjerg pointed out that a greater response in those with the highest reversibility suggests these patients have a phenotype in which bronchodilation is a more important driver of disease than is inflammation.
While conceding that this was possible, Dr. Singh cautioned that he considers these predictors of response to be “exploratory.” He believes that the TRIMARIN/TRIGGER studies were not designed to tease out the relative importance of mechanisms of asthma in response to the assigned therapies. However, he believes the response predictor analysis is a step in this direction, which might be valuable for better individualizing therapy.
The studies were funded by Chiesi Farmaceutici. Dr. Singh reports no potential conflicts of interest.
Virchow JC et al. Lancet. 2019 Sep 30. doi. org/10.1016/S0140-6736(19)32215-9.
MADRID – Two newly published but previously reported phase 3 trials associated triple therapy in a single inhaler with a 23% reduction (P = .008) in asthma exacerbations relative to a two-drug inhaler, but fresh data from a prespecified analysis presented at the annual congress of the European Respiratory Society has identified those patients most likely to benefit.
“Six easily identifiable factors appear to be associated with the most prominent response to treatment and may help in the treatment step-up decision at the point of care,” reported Dave Singh, MD, professor in the division of infection, immunity, and respiratory medicine, University of Manchester (England).
The primary results of these trials were presented several months ago at the 2019 American Thoracic Society (ATS) meeting, but the full data were published on the day that Dr. Singh spoke at the ERS.
To identify predictors of response, the pooled analysis of TRIMARIN and TRIGGER was prespecified. Both of these trials, which were similarly designed, compared a single inhaler of inhaled corticosteroids (ICS), long-acting beta agonist (LABA), and long-acting muscarinic antagonist (LAMA) to a single ICS/LABA inhaler.
On the basis of risk for severe exacerbations, greater protection from triple therapy relative to a conventional ICS/LABA inhaler was identified for those with a high degree of reversibility (defined as greater than 400 mL) relative to those with a lower degree (RR, 0.729; P = .024), those with a body mass index less than 25 kg/m2 relative to a higher BMI (RR, 0.570; P = .005), those with only one exacerbation in the previous 12 months relative to those with more (RR, 0.731; P = .009), never-smokers relative to those with smoking history (RR, 0.764; P = .013), those younger than age 65 years relative to older (RR, 0.770; P = .17), and males relative to females (RR, 0.651; P = .009).
“This gives us six factors to consider when you are thinking about stepping up to triple therapy and are trying to determine which patients would benefit the most,” Dr. Singh said.
Both the TRIMARIN and the TRIGGER trials were double blind and placebo controlled. In both, the experimental arm was a single inhaler triple therapy of the ICS beclomethasone, the LABA formoterol, and the LAMA glycopyrronium. The control arm was a single inhaler combination of beclomethasone and formoterol. All inhalers were used twice daily.
TRIMARIN, with 171 participating sites in 16 countries, randomized 1,155 patients to the triple-drug inhaler with a moderate dose of ICS (100 mcg) or to the ICS/LABA inhaler. In TRIGGER, with 221 sites in 17 countries, 1,437 patients were randomized to one of three arms. Both the triple-drug inhaler arm and the ICS/LABA arm contained a higher dose of ICS (200 mcg) than in TRIMARIN. In an open-label third arm, patients also received the higher dose of ICS plus LABA and a second inhaler with tiotropium. The formoterol dose in all arms of both studies was 6 mcg.
As reported at the ATS and now published in the Lancet, the reduction in exacerbations on single inhaler triple therapy relative to ICS/LABA was significant when the data were pooled (even though the reduction in the TRIGGER study fell short of statistical significance). The median improvement in lung function for single inhaler triple therapy relative to ICS/LABA was significant in both TRIMARIN (57 mL; P = .008) and TRIGGER (73 mL; P = .0025).
In discussing the new pooled analysis of response predictors in TRIMARIN/TRIGGER, the ERS-invited discussant, Celeste M. Porsbjerg, MD, Bispebjerg Hospital, Copenhagen, expressed particular interest in reversibility. A positive reversibility test to salbutamol was an entry criterion for both trials, but Dr. Porsbjerg pointed out that a greater response in those with the highest reversibility suggests these patients have a phenotype in which bronchodilation is a more important driver of disease than is inflammation.
While conceding that this was possible, Dr. Singh cautioned that he considers these predictors of response to be “exploratory.” He believes that the TRIMARIN/TRIGGER studies were not designed to tease out the relative importance of mechanisms of asthma in response to the assigned therapies. However, he believes the response predictor analysis is a step in this direction, which might be valuable for better individualizing therapy.
The studies were funded by Chiesi Farmaceutici. Dr. Singh reports no potential conflicts of interest.
Virchow JC et al. Lancet. 2019 Sep 30. doi. org/10.1016/S0140-6736(19)32215-9.
REPORTING FROM ERS 2019
NIOSH Releases Virtual Toolkit for Emergency Responders
When first responders arrive at a scene where illicit drugs may be present, they could be at risk of dangerous exposure. They might inhale drugs; they can have contact through mucous membranes or through needlesticks.
A major concern is exposure to fentanyl or its analogues, which can lead to symptoms, including rapid onset of life-threatening respiratory depression. The exception is skin contact, which is not expected to have toxic effects if the visible contamination is removed promptly.
To help EMS providers and other responders protect themselves, the National Institute for Occupational Safety and Health (NIOSH) has released a new virtual toolkit with videos, infographics, and postcards based on NIOSH safety recommendations.
The resources highlight how best to assess the scene for hazards that may indicate the presence of illicit drugs and what to do—for example, use soap and water, not hand sanitizer (it doesn’t remove illicit drugs and may increase exposure), and don’t eat, drink, smoke, or use the bathroom in the affected area. The infographics also show how to decontaminate and prevent “take-home exposure” to protect responders’ families. The guidelines extend to procedures for protecting working dogs exposed to the drugs.
NIOSH notes that it has no occupational exposure data on fentanyl or its analogues for emergency responders. The recommendations are based on the reported toxicity and the chemical and physical properties of fentanyl and its analogues, NIOSH guidance for similar chemicals, recommendations from previous NIOSH health hazard evaluation reports, and “the basic principles of industrial hygiene.” As new research becomes available, NIOSH says, the recommendations will be updated.
The toolkit resources are shareable and available for disseminating via print, social media, text, and more. The kit is accessible at https://www.cdc.gov/niosh/topics/fentanyl/toolkit.html.
When first responders arrive at a scene where illicit drugs may be present, they could be at risk of dangerous exposure. They might inhale drugs; they can have contact through mucous membranes or through needlesticks.
A major concern is exposure to fentanyl or its analogues, which can lead to symptoms, including rapid onset of life-threatening respiratory depression. The exception is skin contact, which is not expected to have toxic effects if the visible contamination is removed promptly.
To help EMS providers and other responders protect themselves, the National Institute for Occupational Safety and Health (NIOSH) has released a new virtual toolkit with videos, infographics, and postcards based on NIOSH safety recommendations.
The resources highlight how best to assess the scene for hazards that may indicate the presence of illicit drugs and what to do—for example, use soap and water, not hand sanitizer (it doesn’t remove illicit drugs and may increase exposure), and don’t eat, drink, smoke, or use the bathroom in the affected area. The infographics also show how to decontaminate and prevent “take-home exposure” to protect responders’ families. The guidelines extend to procedures for protecting working dogs exposed to the drugs.
NIOSH notes that it has no occupational exposure data on fentanyl or its analogues for emergency responders. The recommendations are based on the reported toxicity and the chemical and physical properties of fentanyl and its analogues, NIOSH guidance for similar chemicals, recommendations from previous NIOSH health hazard evaluation reports, and “the basic principles of industrial hygiene.” As new research becomes available, NIOSH says, the recommendations will be updated.
The toolkit resources are shareable and available for disseminating via print, social media, text, and more. The kit is accessible at https://www.cdc.gov/niosh/topics/fentanyl/toolkit.html.
When first responders arrive at a scene where illicit drugs may be present, they could be at risk of dangerous exposure. They might inhale drugs; they can have contact through mucous membranes or through needlesticks.
A major concern is exposure to fentanyl or its analogues, which can lead to symptoms, including rapid onset of life-threatening respiratory depression. The exception is skin contact, which is not expected to have toxic effects if the visible contamination is removed promptly.
To help EMS providers and other responders protect themselves, the National Institute for Occupational Safety and Health (NIOSH) has released a new virtual toolkit with videos, infographics, and postcards based on NIOSH safety recommendations.
The resources highlight how best to assess the scene for hazards that may indicate the presence of illicit drugs and what to do—for example, use soap and water, not hand sanitizer (it doesn’t remove illicit drugs and may increase exposure), and don’t eat, drink, smoke, or use the bathroom in the affected area. The infographics also show how to decontaminate and prevent “take-home exposure” to protect responders’ families. The guidelines extend to procedures for protecting working dogs exposed to the drugs.
NIOSH notes that it has no occupational exposure data on fentanyl or its analogues for emergency responders. The recommendations are based on the reported toxicity and the chemical and physical properties of fentanyl and its analogues, NIOSH guidance for similar chemicals, recommendations from previous NIOSH health hazard evaluation reports, and “the basic principles of industrial hygiene.” As new research becomes available, NIOSH says, the recommendations will be updated.
The toolkit resources are shareable and available for disseminating via print, social media, text, and more. The kit is accessible at https://www.cdc.gov/niosh/topics/fentanyl/toolkit.html.
Multicenter trial backs pirfenidone for unclassifiable interstitial lung disease
MADRID – according to results of a late breaker, placebo-controlled, multinational trial presented at the annual congress of the European Respiratory Society.
For preservation of lung function as monitored with forced vital capacity (FVC), pirfenidone provided a large and highly statistically significant advantage over placebo in a phase 2 trial that randomized 253 uILD patients to 2,403 mg pirfenidone or placebo, according to Toby M. Maher, MD, head of the Fibrosis Research Group for the National Heart and Lung Institute, Imperial College, London.
At 24 weeks, FVC lung function declined by just 17.8 mL in the pirfenidone group vs. 113 mL in the placebo group (P = .002). The results, published simultaneously with Dr. Maher’s ERS presentation in The Lancet Respiratory Medicine, are particularly encouraging because there are no currently approved treatments for uILD, according to Dr. Maher.
However, the data from this study, even though it was double blind and involved 70 participating centers in 14 countries, come with an asterisk. The significant FVC advantage was documented with in-hospital measurements, but this was a secondary, not the primary, endpoint. Measurements with hand-held spirometry, which was the primary endpoint, proved to be uninterpretable due to intra-individual variability.
“We had hoped that daily home spirometry would give us more information of the patient’s trajectory over time,” said Dr. Maher, who blames himself for selecting hand-held device measurements as the primary endpoint. In the end, the variability in the home hand-held spirometry data prevented the planned statistical testing.
“There were issues with the hand-held devices we had not anticipated,” Dr. Maher reported. However, hospital-based measurement, which has long been the “regulatory standard” in ILD trials “supports the conclusion that pirfenidone was effective.”
The conclusion is also supported by other secondary outcomes and analyses. For example, the categorical declines in FVC of greater than 5% (37.0% vs. 58.7%; P = .001) and greater than 10% (14.2% vs. 27.9%; P = .011) both favored pirfenidone. There were no between-group differences in progression-free survival at 24 weeks, but events were low in both study arms over this time period.
There was evidence of functional benefit for pirfenidone relative to placebo, such as a smaller decline in the 6-minute walk test (–2 vs. –26.7 M, P = .04). Treatment favoring pirfenidone over placebo was observed across subgroups defined by age, gender, baseline lung function, and presence or absence of interstitial pneumonia with autoimmune features.
Pirfenidone was generally well tolerated with side effects similar to those reported in other studies. The rate of treatment-related discontinuation was 12.6% on pirfenidone versus 0.8% on placebo. The most frequent adverse events, all of which were more common in the pirfenidone group, were gastrointestinal complaints (47.2% vs. 25.8%), rash (10.2% vs. 7.3%), and dizziness (7.9% vs. 0.8%). Rates of photosensitivity were higher in the experimental arm (7.9% vs. 1.8%), but low relative to previous studies, potentially because of greater emphasis on sun protection, Dr. Maher reported.
About 10%-15% of patients with ILD have an unclassifiable type, he noted. Although it is possible for uILD to be a missed diagnosis of an established ILD type, Dr. Maher reported that participating centers for this study were specifically selected for their expertise in ILD. He noted that more than 45% of patients were deemed uILD on the basis of biopsy.
The ERS-invited discussant of this trial, Martin Kolb, MD, professor of respirology, McMaster University, Hamilton, Ont., called the data “strong.” He suggested the data are particularly encouraging in the context of the lack of approved therapies for uILD.
Despite the fact that benefit of pirfenidone was not established on the primary endpoint, Dr. Maher contended that this is a positive study that can be used to design future investigations. “When we use the normal standard endpoint for the study, we see a clear benefit of pirfenidone over placebo.”
Dr. Maher reported no potential conflicts of interest.
SOURCE: Maher TM et al. Lancet Respir Med. 2019 Sep 29. doi: 10.1016/S2213-2600(19)30341-8.
MADRID – according to results of a late breaker, placebo-controlled, multinational trial presented at the annual congress of the European Respiratory Society.
For preservation of lung function as monitored with forced vital capacity (FVC), pirfenidone provided a large and highly statistically significant advantage over placebo in a phase 2 trial that randomized 253 uILD patients to 2,403 mg pirfenidone or placebo, according to Toby M. Maher, MD, head of the Fibrosis Research Group for the National Heart and Lung Institute, Imperial College, London.
At 24 weeks, FVC lung function declined by just 17.8 mL in the pirfenidone group vs. 113 mL in the placebo group (P = .002). The results, published simultaneously with Dr. Maher’s ERS presentation in The Lancet Respiratory Medicine, are particularly encouraging because there are no currently approved treatments for uILD, according to Dr. Maher.
However, the data from this study, even though it was double blind and involved 70 participating centers in 14 countries, come with an asterisk. The significant FVC advantage was documented with in-hospital measurements, but this was a secondary, not the primary, endpoint. Measurements with hand-held spirometry, which was the primary endpoint, proved to be uninterpretable due to intra-individual variability.
“We had hoped that daily home spirometry would give us more information of the patient’s trajectory over time,” said Dr. Maher, who blames himself for selecting hand-held device measurements as the primary endpoint. In the end, the variability in the home hand-held spirometry data prevented the planned statistical testing.
“There were issues with the hand-held devices we had not anticipated,” Dr. Maher reported. However, hospital-based measurement, which has long been the “regulatory standard” in ILD trials “supports the conclusion that pirfenidone was effective.”
The conclusion is also supported by other secondary outcomes and analyses. For example, the categorical declines in FVC of greater than 5% (37.0% vs. 58.7%; P = .001) and greater than 10% (14.2% vs. 27.9%; P = .011) both favored pirfenidone. There were no between-group differences in progression-free survival at 24 weeks, but events were low in both study arms over this time period.
There was evidence of functional benefit for pirfenidone relative to placebo, such as a smaller decline in the 6-minute walk test (–2 vs. –26.7 M, P = .04). Treatment favoring pirfenidone over placebo was observed across subgroups defined by age, gender, baseline lung function, and presence or absence of interstitial pneumonia with autoimmune features.
Pirfenidone was generally well tolerated with side effects similar to those reported in other studies. The rate of treatment-related discontinuation was 12.6% on pirfenidone versus 0.8% on placebo. The most frequent adverse events, all of which were more common in the pirfenidone group, were gastrointestinal complaints (47.2% vs. 25.8%), rash (10.2% vs. 7.3%), and dizziness (7.9% vs. 0.8%). Rates of photosensitivity were higher in the experimental arm (7.9% vs. 1.8%), but low relative to previous studies, potentially because of greater emphasis on sun protection, Dr. Maher reported.
About 10%-15% of patients with ILD have an unclassifiable type, he noted. Although it is possible for uILD to be a missed diagnosis of an established ILD type, Dr. Maher reported that participating centers for this study were specifically selected for their expertise in ILD. He noted that more than 45% of patients were deemed uILD on the basis of biopsy.
The ERS-invited discussant of this trial, Martin Kolb, MD, professor of respirology, McMaster University, Hamilton, Ont., called the data “strong.” He suggested the data are particularly encouraging in the context of the lack of approved therapies for uILD.
Despite the fact that benefit of pirfenidone was not established on the primary endpoint, Dr. Maher contended that this is a positive study that can be used to design future investigations. “When we use the normal standard endpoint for the study, we see a clear benefit of pirfenidone over placebo.”
Dr. Maher reported no potential conflicts of interest.
SOURCE: Maher TM et al. Lancet Respir Med. 2019 Sep 29. doi: 10.1016/S2213-2600(19)30341-8.
MADRID – according to results of a late breaker, placebo-controlled, multinational trial presented at the annual congress of the European Respiratory Society.
For preservation of lung function as monitored with forced vital capacity (FVC), pirfenidone provided a large and highly statistically significant advantage over placebo in a phase 2 trial that randomized 253 uILD patients to 2,403 mg pirfenidone or placebo, according to Toby M. Maher, MD, head of the Fibrosis Research Group for the National Heart and Lung Institute, Imperial College, London.
At 24 weeks, FVC lung function declined by just 17.8 mL in the pirfenidone group vs. 113 mL in the placebo group (P = .002). The results, published simultaneously with Dr. Maher’s ERS presentation in The Lancet Respiratory Medicine, are particularly encouraging because there are no currently approved treatments for uILD, according to Dr. Maher.
However, the data from this study, even though it was double blind and involved 70 participating centers in 14 countries, come with an asterisk. The significant FVC advantage was documented with in-hospital measurements, but this was a secondary, not the primary, endpoint. Measurements with hand-held spirometry, which was the primary endpoint, proved to be uninterpretable due to intra-individual variability.
“We had hoped that daily home spirometry would give us more information of the patient’s trajectory over time,” said Dr. Maher, who blames himself for selecting hand-held device measurements as the primary endpoint. In the end, the variability in the home hand-held spirometry data prevented the planned statistical testing.
“There were issues with the hand-held devices we had not anticipated,” Dr. Maher reported. However, hospital-based measurement, which has long been the “regulatory standard” in ILD trials “supports the conclusion that pirfenidone was effective.”
The conclusion is also supported by other secondary outcomes and analyses. For example, the categorical declines in FVC of greater than 5% (37.0% vs. 58.7%; P = .001) and greater than 10% (14.2% vs. 27.9%; P = .011) both favored pirfenidone. There were no between-group differences in progression-free survival at 24 weeks, but events were low in both study arms over this time period.
There was evidence of functional benefit for pirfenidone relative to placebo, such as a smaller decline in the 6-minute walk test (–2 vs. –26.7 M, P = .04). Treatment favoring pirfenidone over placebo was observed across subgroups defined by age, gender, baseline lung function, and presence or absence of interstitial pneumonia with autoimmune features.
Pirfenidone was generally well tolerated with side effects similar to those reported in other studies. The rate of treatment-related discontinuation was 12.6% on pirfenidone versus 0.8% on placebo. The most frequent adverse events, all of which were more common in the pirfenidone group, were gastrointestinal complaints (47.2% vs. 25.8%), rash (10.2% vs. 7.3%), and dizziness (7.9% vs. 0.8%). Rates of photosensitivity were higher in the experimental arm (7.9% vs. 1.8%), but low relative to previous studies, potentially because of greater emphasis on sun protection, Dr. Maher reported.
About 10%-15% of patients with ILD have an unclassifiable type, he noted. Although it is possible for uILD to be a missed diagnosis of an established ILD type, Dr. Maher reported that participating centers for this study were specifically selected for their expertise in ILD. He noted that more than 45% of patients were deemed uILD on the basis of biopsy.
The ERS-invited discussant of this trial, Martin Kolb, MD, professor of respirology, McMaster University, Hamilton, Ont., called the data “strong.” He suggested the data are particularly encouraging in the context of the lack of approved therapies for uILD.
Despite the fact that benefit of pirfenidone was not established on the primary endpoint, Dr. Maher contended that this is a positive study that can be used to design future investigations. “When we use the normal standard endpoint for the study, we see a clear benefit of pirfenidone over placebo.”
Dr. Maher reported no potential conflicts of interest.
SOURCE: Maher TM et al. Lancet Respir Med. 2019 Sep 29. doi: 10.1016/S2213-2600(19)30341-8.
REPORTING FROM ERS 2019
VA Health Care Facilities Enter a New Smoke-Free Era
The updated smoking policy goes into effect for employees, patients, visitors, volunteers, contractors, and vendors, whether they smoke cigarettes, cigars, pipes, or even electronic and vaping devices, and whenever they are on the grounds of VA health care facilities, including parking areas.
The new policy comes after the VA reviewed research on second- and thirdhand smoke and best practices in the health care industry. “There is no risk-free level of exposure to tobacco smoke,” the VA’s Smokefree website says. Overwhelming evidence shows exposure to secondhand smoke has significant medical risks. Moreover, a growing body of evidence shows exposure to thirdhand smoke (residual nicotine and other chemicals left on indoor surfaces) also is a health hazard. The residue is thought to react with indoor pollutants to create a toxic mix that clings long after smoking has stopped and cannot be eliminated by opening windows, or using fans, or other means of clearing rooms.
“We are not alone in recognizing the importance of creating a smoke-free campus,” said VA Secretary Robert Wilkie. He notes that as of 2014, 4000 health care facilities and 4 national health care systems in the US have implemented smoke-free grounds.
National Association of Government employees will begin implementing the policy as of October 1, and have until January 1, 2020, to fully comply. Smoking shelters will be closed, although each facility will independently determine the disposition of smoking areas and shelters.
The new policy does not mean anyone has to quit smoking but to encourage quitting, the VA offers resources, including www.publichealth.va.gov/smoking/quit/index.asp. More tips and tools are available at the Smokefree Veteran website: https://veterans.smokefree.gov. SmokefreeVET is a text-messaging program (https://veterans.smokefree.gov/tools-tips-vet/smokefreevet) that provides 24/7 support to help veterans quit for good. Employees can contact their facility for resources.
The policies are available at https://www.va.gov/health/smokefree.
The updated smoking policy goes into effect for employees, patients, visitors, volunteers, contractors, and vendors, whether they smoke cigarettes, cigars, pipes, or even electronic and vaping devices, and whenever they are on the grounds of VA health care facilities, including parking areas.
The new policy comes after the VA reviewed research on second- and thirdhand smoke and best practices in the health care industry. “There is no risk-free level of exposure to tobacco smoke,” the VA’s Smokefree website says. Overwhelming evidence shows exposure to secondhand smoke has significant medical risks. Moreover, a growing body of evidence shows exposure to thirdhand smoke (residual nicotine and other chemicals left on indoor surfaces) also is a health hazard. The residue is thought to react with indoor pollutants to create a toxic mix that clings long after smoking has stopped and cannot be eliminated by opening windows, or using fans, or other means of clearing rooms.
“We are not alone in recognizing the importance of creating a smoke-free campus,” said VA Secretary Robert Wilkie. He notes that as of 2014, 4000 health care facilities and 4 national health care systems in the US have implemented smoke-free grounds.
National Association of Government employees will begin implementing the policy as of October 1, and have until January 1, 2020, to fully comply. Smoking shelters will be closed, although each facility will independently determine the disposition of smoking areas and shelters.
The new policy does not mean anyone has to quit smoking but to encourage quitting, the VA offers resources, including www.publichealth.va.gov/smoking/quit/index.asp. More tips and tools are available at the Smokefree Veteran website: https://veterans.smokefree.gov. SmokefreeVET is a text-messaging program (https://veterans.smokefree.gov/tools-tips-vet/smokefreevet) that provides 24/7 support to help veterans quit for good. Employees can contact their facility for resources.
The policies are available at https://www.va.gov/health/smokefree.
The updated smoking policy goes into effect for employees, patients, visitors, volunteers, contractors, and vendors, whether they smoke cigarettes, cigars, pipes, or even electronic and vaping devices, and whenever they are on the grounds of VA health care facilities, including parking areas.
The new policy comes after the VA reviewed research on second- and thirdhand smoke and best practices in the health care industry. “There is no risk-free level of exposure to tobacco smoke,” the VA’s Smokefree website says. Overwhelming evidence shows exposure to secondhand smoke has significant medical risks. Moreover, a growing body of evidence shows exposure to thirdhand smoke (residual nicotine and other chemicals left on indoor surfaces) also is a health hazard. The residue is thought to react with indoor pollutants to create a toxic mix that clings long after smoking has stopped and cannot be eliminated by opening windows, or using fans, or other means of clearing rooms.
“We are not alone in recognizing the importance of creating a smoke-free campus,” said VA Secretary Robert Wilkie. He notes that as of 2014, 4000 health care facilities and 4 national health care systems in the US have implemented smoke-free grounds.
National Association of Government employees will begin implementing the policy as of October 1, and have until January 1, 2020, to fully comply. Smoking shelters will be closed, although each facility will independently determine the disposition of smoking areas and shelters.
The new policy does not mean anyone has to quit smoking but to encourage quitting, the VA offers resources, including www.publichealth.va.gov/smoking/quit/index.asp. More tips and tools are available at the Smokefree Veteran website: https://veterans.smokefree.gov. SmokefreeVET is a text-messaging program (https://veterans.smokefree.gov/tools-tips-vet/smokefreevet) that provides 24/7 support to help veterans quit for good. Employees can contact their facility for resources.
The policies are available at https://www.va.gov/health/smokefree.
Lefamulin found noninferior to moxifloxacin for bacterial pneumonia
Persistent high rates of bacterial resistance to current treatments have created the need for more options, especially for the treatment of community-acquired bacterial pneumonia (CABP), which remains a leading cause of hospitalization and death in the United States, wrote Elizabeth Alexander, MD, of Nabriva Therapeutics in King of Prussia, Penn., and colleagues. Lefamulin, “the first pleuromutilin antibiotic approved for intravenous and oral use in humans,” has demonstrated activity against many CABP-causing pathogens, including some not susceptible to other classes of antimicrobials, they noted.
Findings of Lefamulin Evaluation Against Pneumonia 2 (LEAP2) were published in JAMA. In this study, the researchers randomized 370 patients to 600 mg of oral lefamulin every 12 hours for 5 days and 368 patients to 400 mg of oral moxifloxacin every 24 hours for 7 days.
Early clinical response rates at 96 hours were 90.8% for both medications (difference of 0.1%). In addition, the rates of clinical response success were similar between the groups in both the modified intent-to-treat population (87.5% with lefamulin and 89.1% with moxifloxacin) and the clinically evaluable population (89.7% with lefamulin and 93.6% with moxifloxacin).
Gastrointestinal issues of diarrhea and nausea were the two most frequently reported treatment-emergent adverse events in both groups. Both conditions occurred more often in the lefamulin group, compared with the moxifloxacin group, but the differences were not significant (12.2% vs. 1.1% and 5.2% vs. 1.9%, respectively).
The study findings were limited by several factors including strict exclusion criteria that may limit the generalizability of the results, as well as a lack of testing for viral copathogens, low recovery of resistant pathogens, and possible misclassification of patient ethnicity, the researchers noted.
However, the results were strengthened by the randomized design, inclusion of patients with more severe CABP, and low rate of discontinuation, they said. The data support previous studies of lefamulin. Its lack of cross-resistance to other drug classes, coverage of typical and atypical CABP pathogens, and options for both oral and intravenous use suggest that it “may provide an alternative approach for the treatment of vulnerable patients,” the researchers said.
The study was supported by Nabriva Therapeutics. Dr. Alexander and several coauthors are employees of Nabriva Therapeutics and own stock in the company.
SOURCE: Alexander E et al. JAMA. 2019 Sep 27. doi:10.1001/jama.2019.15468.
“The development and approval of a new antibiotic is a rare occurrence and a reason to celebrate” given the scientific, regulatory, and economic challenges to antibiotic development, wrote Preeti N. Malani, MD, in an accompanying editorial. Lefamulin in both oral and intravenous forms was approved by the Food and Drug Administration in August 2019 for the treatment of community-acquired bacterial pneumonia, Dr. Malani said.
Lefamulin will likely be an expensive option. According to a manufacturer press release, lefamulin may cost $205/day for intravenous treatment and $275/day for oral treatment. “This is severalfold more than moxifloxacin or levofloxacin, which are the most commonly prescribed fluoroquinolones for CABP [community-acquired bacterial pneumonia],” said Dr. Malani. However, the addition of lefamulin to the array of antibiotics is important because of the persistent burden of bacterial pneumonia as an indication for antibiotic use, Dr. Malani emphasized.
Dr. Malani is affiliated with the University of Michigan, Ann Arbor, and serves as an associate editor of JAMA, but had no financial conflicts to disclose. These remarks were taken from an accompanying editorial (JAMA. 2019 Sep 27. doi:10.1001/jama.2019.16215).
“The development and approval of a new antibiotic is a rare occurrence and a reason to celebrate” given the scientific, regulatory, and economic challenges to antibiotic development, wrote Preeti N. Malani, MD, in an accompanying editorial. Lefamulin in both oral and intravenous forms was approved by the Food and Drug Administration in August 2019 for the treatment of community-acquired bacterial pneumonia, Dr. Malani said.
Lefamulin will likely be an expensive option. According to a manufacturer press release, lefamulin may cost $205/day for intravenous treatment and $275/day for oral treatment. “This is severalfold more than moxifloxacin or levofloxacin, which are the most commonly prescribed fluoroquinolones for CABP [community-acquired bacterial pneumonia],” said Dr. Malani. However, the addition of lefamulin to the array of antibiotics is important because of the persistent burden of bacterial pneumonia as an indication for antibiotic use, Dr. Malani emphasized.
Dr. Malani is affiliated with the University of Michigan, Ann Arbor, and serves as an associate editor of JAMA, but had no financial conflicts to disclose. These remarks were taken from an accompanying editorial (JAMA. 2019 Sep 27. doi:10.1001/jama.2019.16215).
“The development and approval of a new antibiotic is a rare occurrence and a reason to celebrate” given the scientific, regulatory, and economic challenges to antibiotic development, wrote Preeti N. Malani, MD, in an accompanying editorial. Lefamulin in both oral and intravenous forms was approved by the Food and Drug Administration in August 2019 for the treatment of community-acquired bacterial pneumonia, Dr. Malani said.
Lefamulin will likely be an expensive option. According to a manufacturer press release, lefamulin may cost $205/day for intravenous treatment and $275/day for oral treatment. “This is severalfold more than moxifloxacin or levofloxacin, which are the most commonly prescribed fluoroquinolones for CABP [community-acquired bacterial pneumonia],” said Dr. Malani. However, the addition of lefamulin to the array of antibiotics is important because of the persistent burden of bacterial pneumonia as an indication for antibiotic use, Dr. Malani emphasized.
Dr. Malani is affiliated with the University of Michigan, Ann Arbor, and serves as an associate editor of JAMA, but had no financial conflicts to disclose. These remarks were taken from an accompanying editorial (JAMA. 2019 Sep 27. doi:10.1001/jama.2019.16215).
Persistent high rates of bacterial resistance to current treatments have created the need for more options, especially for the treatment of community-acquired bacterial pneumonia (CABP), which remains a leading cause of hospitalization and death in the United States, wrote Elizabeth Alexander, MD, of Nabriva Therapeutics in King of Prussia, Penn., and colleagues. Lefamulin, “the first pleuromutilin antibiotic approved for intravenous and oral use in humans,” has demonstrated activity against many CABP-causing pathogens, including some not susceptible to other classes of antimicrobials, they noted.
Findings of Lefamulin Evaluation Against Pneumonia 2 (LEAP2) were published in JAMA. In this study, the researchers randomized 370 patients to 600 mg of oral lefamulin every 12 hours for 5 days and 368 patients to 400 mg of oral moxifloxacin every 24 hours for 7 days.
Early clinical response rates at 96 hours were 90.8% for both medications (difference of 0.1%). In addition, the rates of clinical response success were similar between the groups in both the modified intent-to-treat population (87.5% with lefamulin and 89.1% with moxifloxacin) and the clinically evaluable population (89.7% with lefamulin and 93.6% with moxifloxacin).
Gastrointestinal issues of diarrhea and nausea were the two most frequently reported treatment-emergent adverse events in both groups. Both conditions occurred more often in the lefamulin group, compared with the moxifloxacin group, but the differences were not significant (12.2% vs. 1.1% and 5.2% vs. 1.9%, respectively).
The study findings were limited by several factors including strict exclusion criteria that may limit the generalizability of the results, as well as a lack of testing for viral copathogens, low recovery of resistant pathogens, and possible misclassification of patient ethnicity, the researchers noted.
However, the results were strengthened by the randomized design, inclusion of patients with more severe CABP, and low rate of discontinuation, they said. The data support previous studies of lefamulin. Its lack of cross-resistance to other drug classes, coverage of typical and atypical CABP pathogens, and options for both oral and intravenous use suggest that it “may provide an alternative approach for the treatment of vulnerable patients,” the researchers said.
The study was supported by Nabriva Therapeutics. Dr. Alexander and several coauthors are employees of Nabriva Therapeutics and own stock in the company.
SOURCE: Alexander E et al. JAMA. 2019 Sep 27. doi:10.1001/jama.2019.15468.
Persistent high rates of bacterial resistance to current treatments have created the need for more options, especially for the treatment of community-acquired bacterial pneumonia (CABP), which remains a leading cause of hospitalization and death in the United States, wrote Elizabeth Alexander, MD, of Nabriva Therapeutics in King of Prussia, Penn., and colleagues. Lefamulin, “the first pleuromutilin antibiotic approved for intravenous and oral use in humans,” has demonstrated activity against many CABP-causing pathogens, including some not susceptible to other classes of antimicrobials, they noted.
Findings of Lefamulin Evaluation Against Pneumonia 2 (LEAP2) were published in JAMA. In this study, the researchers randomized 370 patients to 600 mg of oral lefamulin every 12 hours for 5 days and 368 patients to 400 mg of oral moxifloxacin every 24 hours for 7 days.
Early clinical response rates at 96 hours were 90.8% for both medications (difference of 0.1%). In addition, the rates of clinical response success were similar between the groups in both the modified intent-to-treat population (87.5% with lefamulin and 89.1% with moxifloxacin) and the clinically evaluable population (89.7% with lefamulin and 93.6% with moxifloxacin).
Gastrointestinal issues of diarrhea and nausea were the two most frequently reported treatment-emergent adverse events in both groups. Both conditions occurred more often in the lefamulin group, compared with the moxifloxacin group, but the differences were not significant (12.2% vs. 1.1% and 5.2% vs. 1.9%, respectively).
The study findings were limited by several factors including strict exclusion criteria that may limit the generalizability of the results, as well as a lack of testing for viral copathogens, low recovery of resistant pathogens, and possible misclassification of patient ethnicity, the researchers noted.
However, the results were strengthened by the randomized design, inclusion of patients with more severe CABP, and low rate of discontinuation, they said. The data support previous studies of lefamulin. Its lack of cross-resistance to other drug classes, coverage of typical and atypical CABP pathogens, and options for both oral and intravenous use suggest that it “may provide an alternative approach for the treatment of vulnerable patients,” the researchers said.
The study was supported by Nabriva Therapeutics. Dr. Alexander and several coauthors are employees of Nabriva Therapeutics and own stock in the company.
SOURCE: Alexander E et al. JAMA. 2019 Sep 27. doi:10.1001/jama.2019.15468.
FROM JAMA