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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
COVID-19 updates dominate IDWeek lineup
Two of the three late-breaking abstract sessions coming up this week at IDWeek 2021, an annual scientific meeting on infectious diseases, are filled with the most recent evidence on COVID-19 prevention and treatment.
Adarsh Bhimraj, MD, a vice chair of the conference, said in an interview that attendees will leave the virtual conference with an up-to-date view of what’s promising in the fight against COVID-19 globally and what questions are as yet unanswered.
Researchers will also present findings on promising new antibiotics in the pipeline, stewardship efforts, health disparities, telemedicine advances, and emerging pathogens, but at least a quarter of the program is devoted to COVID-19.
“It’s hard to ignore the elephant in the room,” Dr. Bhimraj said.
Vaccine distribution will be among the hot topics at the global conference, he said, in light of the recent decisions by the Food and Drug Administration and the Centers for Disease Control and Prevention to reserve boosters for those at greatest risk.
Although the United States and other high-resource countries are deciding who should get boosters, only 10% of the developing world has received even a single dose, he noted.
The conference will also present a worldwide view of scientific collaboration to address the COVID pandemic and pandemics yet to come, Dr. Bhimraj said.
He highlighted a talk on Oct. 2, to be delivered by South African human rights attorney and social justice activist Fatima Hassan, called “Global Vaccines and Preventive Care Inequities: Implications and Solutions Beyond the Pandemic.”
The session looks ahead to building systems to share resources and knowledge to end deadly outbreaks with an equitable approach.
“We live in a global village,” Dr. Bhimraj said. “It isn’t just the right thing to do, it’s the pragmatic thing to do.”
Controversies in non-COVID diseases
Controversies and new treatments are plentiful in other diseases as well.
- At an HIV session, arguments will be presented regarding the sustainability and practicalities of telemedicine in HIV. Speakers will argue for and against telemedicine as a permanent practice changer for the field.
- In a session on Oct. 1, panelists will discuss pros and cons of information published in preprints versus peer-reviewed journals and how to assess when research findings should lead to practice change.
- Also on Oct. 1, panelists in a symposium will discuss advantages and disadvantages of antifungal treatments for children who have received solid organ transplants.
- Antimicrobial stewardship continues to be a primary topic at IDWeek, this year with additional pandemic challenges. Sessions will address trends in use and diagnostic advances to help in prescribing.
- The pipeline for new antibiotics continues to face barriers regarding production and development. No new classes of antibiotics have been discovered since the 1980s. Pew has that there are too few drugs in development to meet current and anticipated need.
- This year’s program offers a symposium on private-public partnerships to help jump-start development.
- One of the most popular sessions returning this year is “Clinical Trials That Will Change Your Practice,” Dr. Bhimraj said. This year, that session will be reserved for non-COVID infectious disease research. Presenters will summarize the findings of top work published in the past year.
Around-the-world COVID view
Again this year, global experts will present a round-the-clock session called “Chasing the Sun” the day before the main sessions. It will include updates on COVID throughout the world. Barney Graham, MD, PhD, deputy director of the National Institutes of Health’s Vaccine Research Center, will kick off the program with an address on the future of vaccinology. This will be followed by updates on the state of the disease in Central and South America, Japan, Asia Pacific, India, and Africa.
Sandra Harwood, IDWeek conference secretariat, who proposed the idea for the first Chasing the Sun session last year, said in an interview that the updates will highlight particular COVID challenges experienced in various countries.
For example, leaders of India’s session will address why a potentially fatal fungal disease struck many COVID-19 patients in that country. Japan’s update will include how Olympic organizers planned for and dealt with the virus’s threat in Tokyo.
Ms. Harwood said that all the COVID sessions in Chasing the Sun and throughout the program will be free to clinicians inside and outside the conference, thanks to a grant from the CDC.
An address by CDC Director Rochelle Walensky, MD, MPH, on Sept. 30 will wrap up Chasing the Sun and launch the main IDWeek program.
A version of this article first appeared on Medscape.com.
Two of the three late-breaking abstract sessions coming up this week at IDWeek 2021, an annual scientific meeting on infectious diseases, are filled with the most recent evidence on COVID-19 prevention and treatment.
Adarsh Bhimraj, MD, a vice chair of the conference, said in an interview that attendees will leave the virtual conference with an up-to-date view of what’s promising in the fight against COVID-19 globally and what questions are as yet unanswered.
Researchers will also present findings on promising new antibiotics in the pipeline, stewardship efforts, health disparities, telemedicine advances, and emerging pathogens, but at least a quarter of the program is devoted to COVID-19.
“It’s hard to ignore the elephant in the room,” Dr. Bhimraj said.
Vaccine distribution will be among the hot topics at the global conference, he said, in light of the recent decisions by the Food and Drug Administration and the Centers for Disease Control and Prevention to reserve boosters for those at greatest risk.
Although the United States and other high-resource countries are deciding who should get boosters, only 10% of the developing world has received even a single dose, he noted.
The conference will also present a worldwide view of scientific collaboration to address the COVID pandemic and pandemics yet to come, Dr. Bhimraj said.
He highlighted a talk on Oct. 2, to be delivered by South African human rights attorney and social justice activist Fatima Hassan, called “Global Vaccines and Preventive Care Inequities: Implications and Solutions Beyond the Pandemic.”
The session looks ahead to building systems to share resources and knowledge to end deadly outbreaks with an equitable approach.
“We live in a global village,” Dr. Bhimraj said. “It isn’t just the right thing to do, it’s the pragmatic thing to do.”
Controversies in non-COVID diseases
Controversies and new treatments are plentiful in other diseases as well.
- At an HIV session, arguments will be presented regarding the sustainability and practicalities of telemedicine in HIV. Speakers will argue for and against telemedicine as a permanent practice changer for the field.
- In a session on Oct. 1, panelists will discuss pros and cons of information published in preprints versus peer-reviewed journals and how to assess when research findings should lead to practice change.
- Also on Oct. 1, panelists in a symposium will discuss advantages and disadvantages of antifungal treatments for children who have received solid organ transplants.
- Antimicrobial stewardship continues to be a primary topic at IDWeek, this year with additional pandemic challenges. Sessions will address trends in use and diagnostic advances to help in prescribing.
- The pipeline for new antibiotics continues to face barriers regarding production and development. No new classes of antibiotics have been discovered since the 1980s. Pew has that there are too few drugs in development to meet current and anticipated need.
- This year’s program offers a symposium on private-public partnerships to help jump-start development.
- One of the most popular sessions returning this year is “Clinical Trials That Will Change Your Practice,” Dr. Bhimraj said. This year, that session will be reserved for non-COVID infectious disease research. Presenters will summarize the findings of top work published in the past year.
Around-the-world COVID view
Again this year, global experts will present a round-the-clock session called “Chasing the Sun” the day before the main sessions. It will include updates on COVID throughout the world. Barney Graham, MD, PhD, deputy director of the National Institutes of Health’s Vaccine Research Center, will kick off the program with an address on the future of vaccinology. This will be followed by updates on the state of the disease in Central and South America, Japan, Asia Pacific, India, and Africa.
Sandra Harwood, IDWeek conference secretariat, who proposed the idea for the first Chasing the Sun session last year, said in an interview that the updates will highlight particular COVID challenges experienced in various countries.
For example, leaders of India’s session will address why a potentially fatal fungal disease struck many COVID-19 patients in that country. Japan’s update will include how Olympic organizers planned for and dealt with the virus’s threat in Tokyo.
Ms. Harwood said that all the COVID sessions in Chasing the Sun and throughout the program will be free to clinicians inside and outside the conference, thanks to a grant from the CDC.
An address by CDC Director Rochelle Walensky, MD, MPH, on Sept. 30 will wrap up Chasing the Sun and launch the main IDWeek program.
A version of this article first appeared on Medscape.com.
Two of the three late-breaking abstract sessions coming up this week at IDWeek 2021, an annual scientific meeting on infectious diseases, are filled with the most recent evidence on COVID-19 prevention and treatment.
Adarsh Bhimraj, MD, a vice chair of the conference, said in an interview that attendees will leave the virtual conference with an up-to-date view of what’s promising in the fight against COVID-19 globally and what questions are as yet unanswered.
Researchers will also present findings on promising new antibiotics in the pipeline, stewardship efforts, health disparities, telemedicine advances, and emerging pathogens, but at least a quarter of the program is devoted to COVID-19.
“It’s hard to ignore the elephant in the room,” Dr. Bhimraj said.
Vaccine distribution will be among the hot topics at the global conference, he said, in light of the recent decisions by the Food and Drug Administration and the Centers for Disease Control and Prevention to reserve boosters for those at greatest risk.
Although the United States and other high-resource countries are deciding who should get boosters, only 10% of the developing world has received even a single dose, he noted.
The conference will also present a worldwide view of scientific collaboration to address the COVID pandemic and pandemics yet to come, Dr. Bhimraj said.
He highlighted a talk on Oct. 2, to be delivered by South African human rights attorney and social justice activist Fatima Hassan, called “Global Vaccines and Preventive Care Inequities: Implications and Solutions Beyond the Pandemic.”
The session looks ahead to building systems to share resources and knowledge to end deadly outbreaks with an equitable approach.
“We live in a global village,” Dr. Bhimraj said. “It isn’t just the right thing to do, it’s the pragmatic thing to do.”
Controversies in non-COVID diseases
Controversies and new treatments are plentiful in other diseases as well.
- At an HIV session, arguments will be presented regarding the sustainability and practicalities of telemedicine in HIV. Speakers will argue for and against telemedicine as a permanent practice changer for the field.
- In a session on Oct. 1, panelists will discuss pros and cons of information published in preprints versus peer-reviewed journals and how to assess when research findings should lead to practice change.
- Also on Oct. 1, panelists in a symposium will discuss advantages and disadvantages of antifungal treatments for children who have received solid organ transplants.
- Antimicrobial stewardship continues to be a primary topic at IDWeek, this year with additional pandemic challenges. Sessions will address trends in use and diagnostic advances to help in prescribing.
- The pipeline for new antibiotics continues to face barriers regarding production and development. No new classes of antibiotics have been discovered since the 1980s. Pew has that there are too few drugs in development to meet current and anticipated need.
- This year’s program offers a symposium on private-public partnerships to help jump-start development.
- One of the most popular sessions returning this year is “Clinical Trials That Will Change Your Practice,” Dr. Bhimraj said. This year, that session will be reserved for non-COVID infectious disease research. Presenters will summarize the findings of top work published in the past year.
Around-the-world COVID view
Again this year, global experts will present a round-the-clock session called “Chasing the Sun” the day before the main sessions. It will include updates on COVID throughout the world. Barney Graham, MD, PhD, deputy director of the National Institutes of Health’s Vaccine Research Center, will kick off the program with an address on the future of vaccinology. This will be followed by updates on the state of the disease in Central and South America, Japan, Asia Pacific, India, and Africa.
Sandra Harwood, IDWeek conference secretariat, who proposed the idea for the first Chasing the Sun session last year, said in an interview that the updates will highlight particular COVID challenges experienced in various countries.
For example, leaders of India’s session will address why a potentially fatal fungal disease struck many COVID-19 patients in that country. Japan’s update will include how Olympic organizers planned for and dealt with the virus’s threat in Tokyo.
Ms. Harwood said that all the COVID sessions in Chasing the Sun and throughout the program will be free to clinicians inside and outside the conference, thanks to a grant from the CDC.
An address by CDC Director Rochelle Walensky, MD, MPH, on Sept. 30 will wrap up Chasing the Sun and launch the main IDWeek program.
A version of this article first appeared on Medscape.com.
First-in-class TYK inhibitor shows durable effect for psoriasis
of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.
From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).
“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.
The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.
For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).
By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.
By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.
The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.
When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.
On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.
Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.
“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.
In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.
Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.
In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.
The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.
“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.
Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.
“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.
“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.
The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.
From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).
“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.
The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.
For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).
By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.
By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.
The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.
When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.
On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.
Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.
“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.
In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.
Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.
In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.
The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.
“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.
Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.
“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.
“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.
The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.
From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).
“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.
The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.
For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).
By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.
By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.
The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.
When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.
On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.
Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.
“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.
In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.
Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.
In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.
The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.
“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.
Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.
“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.
“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.
The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
Management of pediatric food allergies evolving
The treatment of atopic dermatitis (AD) is undergoing a revolution thanks to biologics. Now, an allergist and a dietitian told pediatric dermatologists that the treatment of a related condition – food allergy – is also undergoing a dramatic transformation as the management approach evolves away from blanket avoidance of allergens.
“Over the past 15 years, we’ve seen a shift from a very passive approach where generally we just advised patients to avoid the things they’re allergic to,” said U.K. pediatric allergist Adam Fox, MBBS, MD, in a presentation at The World Congress of Pediatric Dermatology (WCPD) 2021 Annual Meeting. “Now, we have a much better understanding of how allergy develops and strategies to minimize the risk of allergy happening in the first place,” he said.
According to Carina Venter, PhD, RD, associate professor of pediatrics-allergy/immunology at the University of Colorado, Denver, who also spoke at the conference, an estimated 20% to 30% of patients with AD also have food allergies, and up to 90% of infants with cow’s milk allergy develop skin symptoms.
It may not be necessary for a breastfeeding mother to avoid food allergens if a child is allergic, said Dr. Fox, of Guy’s and St. Thomas’ NHS Foundation Trust, London. “A lot of parents will automatically assume that if their child has an egg or milk allergy, then it’s a good idea to completely eliminate that from their diet if they’re breastfeeding,” but it is “surprisingly uncommon” that this approach makes a difference, he said. “Less goes through the breast milk than people imagine,” he said.
He noted that eliminating foods from the breastfeeding mother’s diet may have negative consequences. “There’s always that risk that if you make life harder for the breastfeeding mom because they’re going to have to avoid all sorts of foods, they’ll be more likely to discontinue breastfeeding. You really need a compelling reason to stop the food.”
As for children themselves, Dr. Fox suggested that there’s often no connection between AD and food allergies. “What will commonly happen when you see and diagnose these kids is that their eczema has been quite significantly undertreated,” he said. “Once you just get them on the right [regimen], they don’t need to be cutting the food out of their diet. It’s just making their life unnecessarily harder.”
Dr. Venter said there may be little choice but to avoid a trigger food if a child develops AD with exposure. However, she noted, it’s important to understand that avoidance of certain foods could make the allergy – and AD – worse. “If you have a child or an adult with atopic dermatitis that’s not controlled by an optimal topical treatment, and you do consider avoidance, we need to be aware that development of more severe IgA-mediated symptoms can happen in a short period of time,” she said.
In a slide that Dr. Venter presented, the dilemma for physicians was expressed this way: “The potential benefit of food avoidance as a management strategy for some patients with AD must now be weighed against the strong evidence that unnecessarily avoiding a food in kids with AD increases the risk of developing anaphylaxis to that food.”
What should pediatric dermatologists do to balance the risks of allergen exposure to the risks that children will develop permanent allergies? Dr. Venter pointed to guidelines about AD that were developed by the U.K.’s National Institute for Health and Care Excellence. She also highlighted the International Milk Allergy in Primary Care recommendations.
She suggested considering creative ways to bypass complete avoidance and boost a child’s tolerance of allergens if possible. “If we’re going to keep a child with eczema on a mold-free diet for a longer period of time, is there perhaps a role for regularly introducing small amounts of yogurt or even small amounts of milk in the child’s diet to at least keep immune tolerance without necessarily aggravating eczema symptoms?”
Dr. Fox has consulted for DBV and Aimmune through his employer, NHS Trust. He serves as president of the British Society for Allergy and Clinical Immunology and as chair of the Allergy UK Health Advisory Board, both of which receive funding from drug companies. Dr. Venter has received support for allergy-related research from the National Peanut Board.
A version of this article first appeared on Medscape.com.
The treatment of atopic dermatitis (AD) is undergoing a revolution thanks to biologics. Now, an allergist and a dietitian told pediatric dermatologists that the treatment of a related condition – food allergy – is also undergoing a dramatic transformation as the management approach evolves away from blanket avoidance of allergens.
“Over the past 15 years, we’ve seen a shift from a very passive approach where generally we just advised patients to avoid the things they’re allergic to,” said U.K. pediatric allergist Adam Fox, MBBS, MD, in a presentation at The World Congress of Pediatric Dermatology (WCPD) 2021 Annual Meeting. “Now, we have a much better understanding of how allergy develops and strategies to minimize the risk of allergy happening in the first place,” he said.
According to Carina Venter, PhD, RD, associate professor of pediatrics-allergy/immunology at the University of Colorado, Denver, who also spoke at the conference, an estimated 20% to 30% of patients with AD also have food allergies, and up to 90% of infants with cow’s milk allergy develop skin symptoms.
It may not be necessary for a breastfeeding mother to avoid food allergens if a child is allergic, said Dr. Fox, of Guy’s and St. Thomas’ NHS Foundation Trust, London. “A lot of parents will automatically assume that if their child has an egg or milk allergy, then it’s a good idea to completely eliminate that from their diet if they’re breastfeeding,” but it is “surprisingly uncommon” that this approach makes a difference, he said. “Less goes through the breast milk than people imagine,” he said.
He noted that eliminating foods from the breastfeeding mother’s diet may have negative consequences. “There’s always that risk that if you make life harder for the breastfeeding mom because they’re going to have to avoid all sorts of foods, they’ll be more likely to discontinue breastfeeding. You really need a compelling reason to stop the food.”
As for children themselves, Dr. Fox suggested that there’s often no connection between AD and food allergies. “What will commonly happen when you see and diagnose these kids is that their eczema has been quite significantly undertreated,” he said. “Once you just get them on the right [regimen], they don’t need to be cutting the food out of their diet. It’s just making their life unnecessarily harder.”
Dr. Venter said there may be little choice but to avoid a trigger food if a child develops AD with exposure. However, she noted, it’s important to understand that avoidance of certain foods could make the allergy – and AD – worse. “If you have a child or an adult with atopic dermatitis that’s not controlled by an optimal topical treatment, and you do consider avoidance, we need to be aware that development of more severe IgA-mediated symptoms can happen in a short period of time,” she said.
In a slide that Dr. Venter presented, the dilemma for physicians was expressed this way: “The potential benefit of food avoidance as a management strategy for some patients with AD must now be weighed against the strong evidence that unnecessarily avoiding a food in kids with AD increases the risk of developing anaphylaxis to that food.”
What should pediatric dermatologists do to balance the risks of allergen exposure to the risks that children will develop permanent allergies? Dr. Venter pointed to guidelines about AD that were developed by the U.K.’s National Institute for Health and Care Excellence. She also highlighted the International Milk Allergy in Primary Care recommendations.
She suggested considering creative ways to bypass complete avoidance and boost a child’s tolerance of allergens if possible. “If we’re going to keep a child with eczema on a mold-free diet for a longer period of time, is there perhaps a role for regularly introducing small amounts of yogurt or even small amounts of milk in the child’s diet to at least keep immune tolerance without necessarily aggravating eczema symptoms?”
Dr. Fox has consulted for DBV and Aimmune through his employer, NHS Trust. He serves as president of the British Society for Allergy and Clinical Immunology and as chair of the Allergy UK Health Advisory Board, both of which receive funding from drug companies. Dr. Venter has received support for allergy-related research from the National Peanut Board.
A version of this article first appeared on Medscape.com.
The treatment of atopic dermatitis (AD) is undergoing a revolution thanks to biologics. Now, an allergist and a dietitian told pediatric dermatologists that the treatment of a related condition – food allergy – is also undergoing a dramatic transformation as the management approach evolves away from blanket avoidance of allergens.
“Over the past 15 years, we’ve seen a shift from a very passive approach where generally we just advised patients to avoid the things they’re allergic to,” said U.K. pediatric allergist Adam Fox, MBBS, MD, in a presentation at The World Congress of Pediatric Dermatology (WCPD) 2021 Annual Meeting. “Now, we have a much better understanding of how allergy develops and strategies to minimize the risk of allergy happening in the first place,” he said.
According to Carina Venter, PhD, RD, associate professor of pediatrics-allergy/immunology at the University of Colorado, Denver, who also spoke at the conference, an estimated 20% to 30% of patients with AD also have food allergies, and up to 90% of infants with cow’s milk allergy develop skin symptoms.
It may not be necessary for a breastfeeding mother to avoid food allergens if a child is allergic, said Dr. Fox, of Guy’s and St. Thomas’ NHS Foundation Trust, London. “A lot of parents will automatically assume that if their child has an egg or milk allergy, then it’s a good idea to completely eliminate that from their diet if they’re breastfeeding,” but it is “surprisingly uncommon” that this approach makes a difference, he said. “Less goes through the breast milk than people imagine,” he said.
He noted that eliminating foods from the breastfeeding mother’s diet may have negative consequences. “There’s always that risk that if you make life harder for the breastfeeding mom because they’re going to have to avoid all sorts of foods, they’ll be more likely to discontinue breastfeeding. You really need a compelling reason to stop the food.”
As for children themselves, Dr. Fox suggested that there’s often no connection between AD and food allergies. “What will commonly happen when you see and diagnose these kids is that their eczema has been quite significantly undertreated,” he said. “Once you just get them on the right [regimen], they don’t need to be cutting the food out of their diet. It’s just making their life unnecessarily harder.”
Dr. Venter said there may be little choice but to avoid a trigger food if a child develops AD with exposure. However, she noted, it’s important to understand that avoidance of certain foods could make the allergy – and AD – worse. “If you have a child or an adult with atopic dermatitis that’s not controlled by an optimal topical treatment, and you do consider avoidance, we need to be aware that development of more severe IgA-mediated symptoms can happen in a short period of time,” she said.
In a slide that Dr. Venter presented, the dilemma for physicians was expressed this way: “The potential benefit of food avoidance as a management strategy for some patients with AD must now be weighed against the strong evidence that unnecessarily avoiding a food in kids with AD increases the risk of developing anaphylaxis to that food.”
What should pediatric dermatologists do to balance the risks of allergen exposure to the risks that children will develop permanent allergies? Dr. Venter pointed to guidelines about AD that were developed by the U.K.’s National Institute for Health and Care Excellence. She also highlighted the International Milk Allergy in Primary Care recommendations.
She suggested considering creative ways to bypass complete avoidance and boost a child’s tolerance of allergens if possible. “If we’re going to keep a child with eczema on a mold-free diet for a longer period of time, is there perhaps a role for regularly introducing small amounts of yogurt or even small amounts of milk in the child’s diet to at least keep immune tolerance without necessarily aggravating eczema symptoms?”
Dr. Fox has consulted for DBV and Aimmune through his employer, NHS Trust. He serves as president of the British Society for Allergy and Clinical Immunology and as chair of the Allergy UK Health Advisory Board, both of which receive funding from drug companies. Dr. Venter has received support for allergy-related research from the National Peanut Board.
A version of this article first appeared on Medscape.com.
What’s the best approach for dysplasia surveillance in IBD?
Chromoendoscopy
Chromoendoscopy is superior in both the detection and long-term management of dysplasia in IBD when compared to high-definition white-light examination. Chromoendoscopy not only enhances dysplasia detection but further improves the definition of these lesions which then facilitates endoscopic management.
Human beings have an innate visual perception limitation due to our inability to perceive depth in the red/green wavelength of light compared to the blue wavelength. All of the improvements in scope magnification and resolution bump up against this fact of our biology. Blue dye enhances our ability to perceive depth in this milieu and therefore detect and define flat lesions.
The superiority of chromoendoscopy when using standard definition colonoscopes has been demonstrated repeatedly and set the stage for the 2015 SCENIC international consensus statement and a seismic shift in our endoscopic management of dysplasia in patients with colitis. This evidence base remains relevant because only 77% of colonoscopies performed in the United States are performed using high-definition equipment. Nearly one-quarter of our patients lack access to the newer equipment and therefore without chromoendoscopy are being surveyed outside of current guidelines.
Since the SCENIC statement multiple studies comparing chromoendoscopy with newer higher resolution colonoscopes have been performed. The vast preponderance of evidence has shown either a trend toward superiority or the outright superiority of chromoendoscopy when compared with high-definition white-light examination in detection and long-term management of dysplasia.
Chromoendoscopy has allowed us to increase our visual vocabulary in describing dysplasia in the setting of colitis and, thus, open the door to further innovation and perhaps adoption of artificial intelligence going forward. Our ability to classify lesions encountered in colitis mucosa has become more precise with the expanded terminology the dye-enhanced high-definition view affords, with the Frankfurt Advanced Chromoendoscopic IBD Lesion Classification being the best and most detailed example.
It is no accident that advanced endoscopists have universally adopted chromoendoscopy for the management of dysplastic lesions whether by mucosal resection or submucosal dissection techniques. Chromoendoscopy is recommended by all society guidelines because of these inherent advantages.
Is high-definition white-light “good enough” for surveilling our patients with colitis? The overall incidence of CRC in IBD has been declining which makes each colonoscopy count more. We are performing up to 88 colonoscopies in patients with colitis to find a single cancer (compared to 8 in non-IBD surveillance patients). We need to be performing fewer and more precise chromoendoscopic examinations. We are otherwise failing to serve our IBD patients by performing too many negative procedures at too high a cost. Our patients deserve more than merely “good enough.”
James F. Marion, MD, is professor of medicine at the Icahn School of Medicine at Mount Sinai and director of education and outreach at The Susan and Leonard Feinstein Inflammatory Bowel Disease Center of The Mount Sinai Hospital, both in New York. He is on the advisory board for Janssen.
High-definition white light endoscopy
Longstanding ulcerative colitis and Crohn’s colitis increase the risk for developing colorectal cancer. The majority of neoplastic lesions are visible endoscopically, and therefore, dye spraying chromoendoscopy (DCE) may not be necessary for all inflammatory bowel disease (IBD) patients undergoing a routine dysplasia surveillance colonoscopy.
High-definition white light (HDWL) endoscopes have higher magnification capacities and pixel density than the standard definition (SD) systems and provide sharper images with fewer artifacts. Although DCE has been proven to be superior to SD, there have been no differences in detection of dysplasia for routine surveillance with use of HDWL compared to DCE.
The SCENIC guidelines key recommendation for optimizing detection and management of dysplasia in IBD is to use a HD colonoscope. Further, based on the recent ACG Practice Guidelines for Dysplasia Screening and Surveillance in 2019, HD colonoscopes are also recommended.
In a network meta-analysis of eight parallel-group randomized controlled trials (RCT), there was very low quality of evidence to support the use of DCE over HDWL. This was contrary to prior, non-RCT studies which suggested that both SD and HDWL were inferior to DCE. More recently, Iacucci and colleagues conducted a randomized noninferiority trial to determine detection rates of neoplastic lesions in IBD patients with longstanding colitis who had inactive disease and enrolled in HDWL, DCE, or virtual chromoendoscopy (VCE) groups. The conclusion was that VCE and HDWL was not inferior to DCE, and HDWL was sufficient in detection of all neoplastic lesions including dysplasia and adenocarcinoma. In another large multicenter, prospective RCT of nine tertiary hospitals in South Korea, the detection rates of colitis-associated dysplasia or all colorectal neoplasia were comparable in HDWL versus high-definition chromoendoscopy. Lastly, a meta-analysis of six RCTs concluded that, although DCE is superior to SD in identification of dysplasia, there was no benefit of DCE compared to HDWL.
In summary, HDWL colonoscopy should be the standard of care for routine dysplasia surveillance in IBD. DCE should be considered in patients who are found to have a dysplastic lesion by HDWL in order to better delineate the lesion margins, endoscopically resect or remove, and for future dysplasia surveillance colonoscopies in the higher-risk IBD patient. Overall, a close and careful examination of the entire colon with use of HDWL is sufficient in detection of dysplasia and for routine surveillance in IBD patients.
Anita Afzali, MD, MPH, AGAF, is medical director of the Inflammatory Bowel Disease Center and program director of the Advanced Inflammatory Bowel Disease Fellowship at Ohio State University in Hilliard, Ohio. She has no relevant conflicts of interest.
These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Chromoendoscopy
Chromoendoscopy is superior in both the detection and long-term management of dysplasia in IBD when compared to high-definition white-light examination. Chromoendoscopy not only enhances dysplasia detection but further improves the definition of these lesions which then facilitates endoscopic management.
Human beings have an innate visual perception limitation due to our inability to perceive depth in the red/green wavelength of light compared to the blue wavelength. All of the improvements in scope magnification and resolution bump up against this fact of our biology. Blue dye enhances our ability to perceive depth in this milieu and therefore detect and define flat lesions.
The superiority of chromoendoscopy when using standard definition colonoscopes has been demonstrated repeatedly and set the stage for the 2015 SCENIC international consensus statement and a seismic shift in our endoscopic management of dysplasia in patients with colitis. This evidence base remains relevant because only 77% of colonoscopies performed in the United States are performed using high-definition equipment. Nearly one-quarter of our patients lack access to the newer equipment and therefore without chromoendoscopy are being surveyed outside of current guidelines.
Since the SCENIC statement multiple studies comparing chromoendoscopy with newer higher resolution colonoscopes have been performed. The vast preponderance of evidence has shown either a trend toward superiority or the outright superiority of chromoendoscopy when compared with high-definition white-light examination in detection and long-term management of dysplasia.
Chromoendoscopy has allowed us to increase our visual vocabulary in describing dysplasia in the setting of colitis and, thus, open the door to further innovation and perhaps adoption of artificial intelligence going forward. Our ability to classify lesions encountered in colitis mucosa has become more precise with the expanded terminology the dye-enhanced high-definition view affords, with the Frankfurt Advanced Chromoendoscopic IBD Lesion Classification being the best and most detailed example.
It is no accident that advanced endoscopists have universally adopted chromoendoscopy for the management of dysplastic lesions whether by mucosal resection or submucosal dissection techniques. Chromoendoscopy is recommended by all society guidelines because of these inherent advantages.
Is high-definition white-light “good enough” for surveilling our patients with colitis? The overall incidence of CRC in IBD has been declining which makes each colonoscopy count more. We are performing up to 88 colonoscopies in patients with colitis to find a single cancer (compared to 8 in non-IBD surveillance patients). We need to be performing fewer and more precise chromoendoscopic examinations. We are otherwise failing to serve our IBD patients by performing too many negative procedures at too high a cost. Our patients deserve more than merely “good enough.”
James F. Marion, MD, is professor of medicine at the Icahn School of Medicine at Mount Sinai and director of education and outreach at The Susan and Leonard Feinstein Inflammatory Bowel Disease Center of The Mount Sinai Hospital, both in New York. He is on the advisory board for Janssen.
High-definition white light endoscopy
Longstanding ulcerative colitis and Crohn’s colitis increase the risk for developing colorectal cancer. The majority of neoplastic lesions are visible endoscopically, and therefore, dye spraying chromoendoscopy (DCE) may not be necessary for all inflammatory bowel disease (IBD) patients undergoing a routine dysplasia surveillance colonoscopy.
High-definition white light (HDWL) endoscopes have higher magnification capacities and pixel density than the standard definition (SD) systems and provide sharper images with fewer artifacts. Although DCE has been proven to be superior to SD, there have been no differences in detection of dysplasia for routine surveillance with use of HDWL compared to DCE.
The SCENIC guidelines key recommendation for optimizing detection and management of dysplasia in IBD is to use a HD colonoscope. Further, based on the recent ACG Practice Guidelines for Dysplasia Screening and Surveillance in 2019, HD colonoscopes are also recommended.
In a network meta-analysis of eight parallel-group randomized controlled trials (RCT), there was very low quality of evidence to support the use of DCE over HDWL. This was contrary to prior, non-RCT studies which suggested that both SD and HDWL were inferior to DCE. More recently, Iacucci and colleagues conducted a randomized noninferiority trial to determine detection rates of neoplastic lesions in IBD patients with longstanding colitis who had inactive disease and enrolled in HDWL, DCE, or virtual chromoendoscopy (VCE) groups. The conclusion was that VCE and HDWL was not inferior to DCE, and HDWL was sufficient in detection of all neoplastic lesions including dysplasia and adenocarcinoma. In another large multicenter, prospective RCT of nine tertiary hospitals in South Korea, the detection rates of colitis-associated dysplasia or all colorectal neoplasia were comparable in HDWL versus high-definition chromoendoscopy. Lastly, a meta-analysis of six RCTs concluded that, although DCE is superior to SD in identification of dysplasia, there was no benefit of DCE compared to HDWL.
In summary, HDWL colonoscopy should be the standard of care for routine dysplasia surveillance in IBD. DCE should be considered in patients who are found to have a dysplastic lesion by HDWL in order to better delineate the lesion margins, endoscopically resect or remove, and for future dysplasia surveillance colonoscopies in the higher-risk IBD patient. Overall, a close and careful examination of the entire colon with use of HDWL is sufficient in detection of dysplasia and for routine surveillance in IBD patients.
Anita Afzali, MD, MPH, AGAF, is medical director of the Inflammatory Bowel Disease Center and program director of the Advanced Inflammatory Bowel Disease Fellowship at Ohio State University in Hilliard, Ohio. She has no relevant conflicts of interest.
These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Chromoendoscopy
Chromoendoscopy is superior in both the detection and long-term management of dysplasia in IBD when compared to high-definition white-light examination. Chromoendoscopy not only enhances dysplasia detection but further improves the definition of these lesions which then facilitates endoscopic management.
Human beings have an innate visual perception limitation due to our inability to perceive depth in the red/green wavelength of light compared to the blue wavelength. All of the improvements in scope magnification and resolution bump up against this fact of our biology. Blue dye enhances our ability to perceive depth in this milieu and therefore detect and define flat lesions.
The superiority of chromoendoscopy when using standard definition colonoscopes has been demonstrated repeatedly and set the stage for the 2015 SCENIC international consensus statement and a seismic shift in our endoscopic management of dysplasia in patients with colitis. This evidence base remains relevant because only 77% of colonoscopies performed in the United States are performed using high-definition equipment. Nearly one-quarter of our patients lack access to the newer equipment and therefore without chromoendoscopy are being surveyed outside of current guidelines.
Since the SCENIC statement multiple studies comparing chromoendoscopy with newer higher resolution colonoscopes have been performed. The vast preponderance of evidence has shown either a trend toward superiority or the outright superiority of chromoendoscopy when compared with high-definition white-light examination in detection and long-term management of dysplasia.
Chromoendoscopy has allowed us to increase our visual vocabulary in describing dysplasia in the setting of colitis and, thus, open the door to further innovation and perhaps adoption of artificial intelligence going forward. Our ability to classify lesions encountered in colitis mucosa has become more precise with the expanded terminology the dye-enhanced high-definition view affords, with the Frankfurt Advanced Chromoendoscopic IBD Lesion Classification being the best and most detailed example.
It is no accident that advanced endoscopists have universally adopted chromoendoscopy for the management of dysplastic lesions whether by mucosal resection or submucosal dissection techniques. Chromoendoscopy is recommended by all society guidelines because of these inherent advantages.
Is high-definition white-light “good enough” for surveilling our patients with colitis? The overall incidence of CRC in IBD has been declining which makes each colonoscopy count more. We are performing up to 88 colonoscopies in patients with colitis to find a single cancer (compared to 8 in non-IBD surveillance patients). We need to be performing fewer and more precise chromoendoscopic examinations. We are otherwise failing to serve our IBD patients by performing too many negative procedures at too high a cost. Our patients deserve more than merely “good enough.”
James F. Marion, MD, is professor of medicine at the Icahn School of Medicine at Mount Sinai and director of education and outreach at The Susan and Leonard Feinstein Inflammatory Bowel Disease Center of The Mount Sinai Hospital, both in New York. He is on the advisory board for Janssen.
High-definition white light endoscopy
Longstanding ulcerative colitis and Crohn’s colitis increase the risk for developing colorectal cancer. The majority of neoplastic lesions are visible endoscopically, and therefore, dye spraying chromoendoscopy (DCE) may not be necessary for all inflammatory bowel disease (IBD) patients undergoing a routine dysplasia surveillance colonoscopy.
High-definition white light (HDWL) endoscopes have higher magnification capacities and pixel density than the standard definition (SD) systems and provide sharper images with fewer artifacts. Although DCE has been proven to be superior to SD, there have been no differences in detection of dysplasia for routine surveillance with use of HDWL compared to DCE.
The SCENIC guidelines key recommendation for optimizing detection and management of dysplasia in IBD is to use a HD colonoscope. Further, based on the recent ACG Practice Guidelines for Dysplasia Screening and Surveillance in 2019, HD colonoscopes are also recommended.
In a network meta-analysis of eight parallel-group randomized controlled trials (RCT), there was very low quality of evidence to support the use of DCE over HDWL. This was contrary to prior, non-RCT studies which suggested that both SD and HDWL were inferior to DCE. More recently, Iacucci and colleagues conducted a randomized noninferiority trial to determine detection rates of neoplastic lesions in IBD patients with longstanding colitis who had inactive disease and enrolled in HDWL, DCE, or virtual chromoendoscopy (VCE) groups. The conclusion was that VCE and HDWL was not inferior to DCE, and HDWL was sufficient in detection of all neoplastic lesions including dysplasia and adenocarcinoma. In another large multicenter, prospective RCT of nine tertiary hospitals in South Korea, the detection rates of colitis-associated dysplasia or all colorectal neoplasia were comparable in HDWL versus high-definition chromoendoscopy. Lastly, a meta-analysis of six RCTs concluded that, although DCE is superior to SD in identification of dysplasia, there was no benefit of DCE compared to HDWL.
In summary, HDWL colonoscopy should be the standard of care for routine dysplasia surveillance in IBD. DCE should be considered in patients who are found to have a dysplastic lesion by HDWL in order to better delineate the lesion margins, endoscopically resect or remove, and for future dysplasia surveillance colonoscopies in the higher-risk IBD patient. Overall, a close and careful examination of the entire colon with use of HDWL is sufficient in detection of dysplasia and for routine surveillance in IBD patients.
Anita Afzali, MD, MPH, AGAF, is medical director of the Inflammatory Bowel Disease Center and program director of the Advanced Inflammatory Bowel Disease Fellowship at Ohio State University in Hilliard, Ohio. She has no relevant conflicts of interest.
These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Retinopathy risk higher in young-onset T2D, more so in men
Men diagnosed with type 2 diabetes (T2D) by the age of 40 years appear significantly more likely to develop retinopathy than men who are diagnosed at an older age, Norwegian researchers report.
In a cross-sectional study of about 10,000 people, men with young-onset T2D were 72% more likely than men aged 50 years or older to have retinopathy.
While an increased retinopathy risk was also seen in women with young-onset T2D versus older women at first, this difference was not significant after adjusting for various confounding factors.
The effect of young-onset diabetes on retinopathy seems to be gender specific, Katrina Tibballs, MD, of the department of general practice at the University of Oslo, reported at the annual meeting of the European Association for the Study of Diabetes.
“In the unadjusted analysis, the odds ratio for retinopathy was substantially higher in both [young-onset] men [odds ratio, 3.0] and women [OR, 2.46], compared with those 50 or older at diabetes diagnosis,” Dr. Tibballs said.
That relationship was not substantially altered after adjustment for variables such as level of education, country background, gender, and body mass index, with adjusted ORs of 2.56 and 2.55 for men and women, respectively.
However, further adjustment to include current age, duration of diabetes, and blood lipids and glycated hemoglobin levels, led to the difference no longer holding for women (OR, 1.34; 95% confidence interval, 0.95-1.89) as it did for men (OR 1.72; 95% CI, 1.29-2.29).
First data in Norwegian population
Cross-sectional data on more than 10,000 people with T2D were used for the analysis. These came from the ROSA4 study, a general practice study conducted across Norway in 2014.
Just over 10% of the study population used in the analysis was under the age of 40 years at diagnosis of T2D; 21% were aged between 40 and 49 years, and 69% were at least 50 years old.
The mean age of those with young-onset T2D, defined as a diagnosis before the age of 40 years, was 33 years. These individuals had a longer disease duration than those in the other age groups (11.4 vs. 10.0 vs. 7.8 years).
“Looking at clinical characteristics, we say that individuals [with young-onset T2D] have a higher level of hemoglobin A1c than those with diabetes onset later in life,” Dr. Tibballs said.
“This is despite a substantially higher proportion [being] treated with insulin and fewer on lifestyle interventions alone.”
Gender differences were seen in A1c levels, with men with young-onset T2D having consistently higher levels than women, with levels increasing with diabetes duration.
Rise in retinopathy faster in men than in women
Dr. Tibballs reported that, not only did the prevalence of retinopathy rise faster in those of a younger age, but it also rose more quickly in men with young-onset T2D than it in their female counterparts.
“Comparing that [young-onset diabetes] and later-onset diabetes in men and women separately, we see a clearly higher prevalence of retinopathy with increasing diabetes duration for [young-onset] men,” she said.
In women, on the other hand, there was “no clear indication of a higher retinopathy prevalence in [young-onset diabetes], except in those with the longest diabetes duration.”
So, what do the results mean for practice? First, they confirm prior work showing that there is a strong association between retinopathy and age at diagnosis of T2D. Second, they suggest that this is despite intensive glucose-lowering treatment.
She speculated that men with young-onset T2D may have had a delayed diagnosis when compared with women and individuals with later onset diabetes, Dr. Tibballs said.
“This may in turn lead to delayed onset of glucose-lowering treatment, allowing for more time with high glycemic exposure and increased risk of acquiring complications, such as retinopathy at the time of diagnosis, or in the first years after,” said Dr. Tibballs.
These are cross-sectional data, “so we can’t say anything about whether this treatment is sufficient, but it is obviously not reducing HbA1c levels as much as we would like” added Dr. Tibballs, who is a primary care physician and PhD student.
The study was supported by The Norwegian Research Fund for General Practice. Dr. Tibballs had no conflicts of interest to disclose.
Men diagnosed with type 2 diabetes (T2D) by the age of 40 years appear significantly more likely to develop retinopathy than men who are diagnosed at an older age, Norwegian researchers report.
In a cross-sectional study of about 10,000 people, men with young-onset T2D were 72% more likely than men aged 50 years or older to have retinopathy.
While an increased retinopathy risk was also seen in women with young-onset T2D versus older women at first, this difference was not significant after adjusting for various confounding factors.
The effect of young-onset diabetes on retinopathy seems to be gender specific, Katrina Tibballs, MD, of the department of general practice at the University of Oslo, reported at the annual meeting of the European Association for the Study of Diabetes.
“In the unadjusted analysis, the odds ratio for retinopathy was substantially higher in both [young-onset] men [odds ratio, 3.0] and women [OR, 2.46], compared with those 50 or older at diabetes diagnosis,” Dr. Tibballs said.
That relationship was not substantially altered after adjustment for variables such as level of education, country background, gender, and body mass index, with adjusted ORs of 2.56 and 2.55 for men and women, respectively.
However, further adjustment to include current age, duration of diabetes, and blood lipids and glycated hemoglobin levels, led to the difference no longer holding for women (OR, 1.34; 95% confidence interval, 0.95-1.89) as it did for men (OR 1.72; 95% CI, 1.29-2.29).
First data in Norwegian population
Cross-sectional data on more than 10,000 people with T2D were used for the analysis. These came from the ROSA4 study, a general practice study conducted across Norway in 2014.
Just over 10% of the study population used in the analysis was under the age of 40 years at diagnosis of T2D; 21% were aged between 40 and 49 years, and 69% were at least 50 years old.
The mean age of those with young-onset T2D, defined as a diagnosis before the age of 40 years, was 33 years. These individuals had a longer disease duration than those in the other age groups (11.4 vs. 10.0 vs. 7.8 years).
“Looking at clinical characteristics, we say that individuals [with young-onset T2D] have a higher level of hemoglobin A1c than those with diabetes onset later in life,” Dr. Tibballs said.
“This is despite a substantially higher proportion [being] treated with insulin and fewer on lifestyle interventions alone.”
Gender differences were seen in A1c levels, with men with young-onset T2D having consistently higher levels than women, with levels increasing with diabetes duration.
Rise in retinopathy faster in men than in women
Dr. Tibballs reported that, not only did the prevalence of retinopathy rise faster in those of a younger age, but it also rose more quickly in men with young-onset T2D than it in their female counterparts.
“Comparing that [young-onset diabetes] and later-onset diabetes in men and women separately, we see a clearly higher prevalence of retinopathy with increasing diabetes duration for [young-onset] men,” she said.
In women, on the other hand, there was “no clear indication of a higher retinopathy prevalence in [young-onset diabetes], except in those with the longest diabetes duration.”
So, what do the results mean for practice? First, they confirm prior work showing that there is a strong association between retinopathy and age at diagnosis of T2D. Second, they suggest that this is despite intensive glucose-lowering treatment.
She speculated that men with young-onset T2D may have had a delayed diagnosis when compared with women and individuals with later onset diabetes, Dr. Tibballs said.
“This may in turn lead to delayed onset of glucose-lowering treatment, allowing for more time with high glycemic exposure and increased risk of acquiring complications, such as retinopathy at the time of diagnosis, or in the first years after,” said Dr. Tibballs.
These are cross-sectional data, “so we can’t say anything about whether this treatment is sufficient, but it is obviously not reducing HbA1c levels as much as we would like” added Dr. Tibballs, who is a primary care physician and PhD student.
The study was supported by The Norwegian Research Fund for General Practice. Dr. Tibballs had no conflicts of interest to disclose.
Men diagnosed with type 2 diabetes (T2D) by the age of 40 years appear significantly more likely to develop retinopathy than men who are diagnosed at an older age, Norwegian researchers report.
In a cross-sectional study of about 10,000 people, men with young-onset T2D were 72% more likely than men aged 50 years or older to have retinopathy.
While an increased retinopathy risk was also seen in women with young-onset T2D versus older women at first, this difference was not significant after adjusting for various confounding factors.
The effect of young-onset diabetes on retinopathy seems to be gender specific, Katrina Tibballs, MD, of the department of general practice at the University of Oslo, reported at the annual meeting of the European Association for the Study of Diabetes.
“In the unadjusted analysis, the odds ratio for retinopathy was substantially higher in both [young-onset] men [odds ratio, 3.0] and women [OR, 2.46], compared with those 50 or older at diabetes diagnosis,” Dr. Tibballs said.
That relationship was not substantially altered after adjustment for variables such as level of education, country background, gender, and body mass index, with adjusted ORs of 2.56 and 2.55 for men and women, respectively.
However, further adjustment to include current age, duration of diabetes, and blood lipids and glycated hemoglobin levels, led to the difference no longer holding for women (OR, 1.34; 95% confidence interval, 0.95-1.89) as it did for men (OR 1.72; 95% CI, 1.29-2.29).
First data in Norwegian population
Cross-sectional data on more than 10,000 people with T2D were used for the analysis. These came from the ROSA4 study, a general practice study conducted across Norway in 2014.
Just over 10% of the study population used in the analysis was under the age of 40 years at diagnosis of T2D; 21% were aged between 40 and 49 years, and 69% were at least 50 years old.
The mean age of those with young-onset T2D, defined as a diagnosis before the age of 40 years, was 33 years. These individuals had a longer disease duration than those in the other age groups (11.4 vs. 10.0 vs. 7.8 years).
“Looking at clinical characteristics, we say that individuals [with young-onset T2D] have a higher level of hemoglobin A1c than those with diabetes onset later in life,” Dr. Tibballs said.
“This is despite a substantially higher proportion [being] treated with insulin and fewer on lifestyle interventions alone.”
Gender differences were seen in A1c levels, with men with young-onset T2D having consistently higher levels than women, with levels increasing with diabetes duration.
Rise in retinopathy faster in men than in women
Dr. Tibballs reported that, not only did the prevalence of retinopathy rise faster in those of a younger age, but it also rose more quickly in men with young-onset T2D than it in their female counterparts.
“Comparing that [young-onset diabetes] and later-onset diabetes in men and women separately, we see a clearly higher prevalence of retinopathy with increasing diabetes duration for [young-onset] men,” she said.
In women, on the other hand, there was “no clear indication of a higher retinopathy prevalence in [young-onset diabetes], except in those with the longest diabetes duration.”
So, what do the results mean for practice? First, they confirm prior work showing that there is a strong association between retinopathy and age at diagnosis of T2D. Second, they suggest that this is despite intensive glucose-lowering treatment.
She speculated that men with young-onset T2D may have had a delayed diagnosis when compared with women and individuals with later onset diabetes, Dr. Tibballs said.
“This may in turn lead to delayed onset of glucose-lowering treatment, allowing for more time with high glycemic exposure and increased risk of acquiring complications, such as retinopathy at the time of diagnosis, or in the first years after,” said Dr. Tibballs.
These are cross-sectional data, “so we can’t say anything about whether this treatment is sufficient, but it is obviously not reducing HbA1c levels as much as we would like” added Dr. Tibballs, who is a primary care physician and PhD student.
The study was supported by The Norwegian Research Fund for General Practice. Dr. Tibballs had no conflicts of interest to disclose.
FROM EASD 2021
Genetic testing for colon cancer: Who, when, and how
Gastroenterologists should be skilled in recognition of patients with inherited risk of colorectal neoplasia. Fay Kastrinos, MD, presented a 49-year-old female who had more than 10 cumulative adenomas and a cecal adenocarcinoma on two colonoscopies, the first of which was performed for evaluation of rectal bleeding. Carol Burke, MD, reviewed the differential diagnosis of adenomatous polyposis (defined as >10 cumulative adenomas).
Germline syndromes include familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and a number of rare germline syndromes. Lynch syndrome should be considered especially for carriers of pathogenic variants in MSH6 who can present with a polyposis phenotype, as well as in children with constitutional mismatch repair deficiency syndrome. Finally, polyposis can be due to smoking, familial clustering, or previous abdominal radiation called therapy-associated polyposis. Polyposis without a known cause is referred to as colonic polyposis of unknown etiology (CPUE).
Dr. Kastrinos reviewed the patient’s three-generation family history of a brother and mother with “polyps” and second-degree relatives with endometrial and colon cancer. Niloy Jewel Samadder, MD, presented on the role of taking a comprehensive family history, tumor tests for Lynch syndrome, selection of genetic test type, and risks, benefits, and alternatives of genetic testing. Dr. Samadder reviewed indications for germline genetic testing for colorectal neoplasia of which the patient met two criteria, namely colorectal cancer under age 50 and 10 or more cumulative adenomas.
The final section was presented by this author on multigene panel testing, in which multiple genes are sequenced simultaneously. This patient’s panel showed two pathogenic variants in the MUTYH gene consistent with MAP, a recessive polyposis syndrome typically with 10s-100 cumulative adenomas. The test also showed a variant of uncertain significance (VUS) which is not clinically actionable. Providers counseling patients on multigene panel testing should discuss the possibility of VUS results (especially in individuals of non-European descent), moderate penetrant genes for which management recommendations are uncertain, or unexpected findings in genes not associated with colonic neoplasia. Studies have shown that the prevalence of finding an inherited syndrome is increased at younger ages of disease onset.
Dr. Kastrinos summarized key points from the session, including hereditary colorectal cancer syndromes are not rare, red flags for inherited syndromes, include early onset colorectal neoplasia and/or numerous relatives with colorectal and other extra-colonic cancer, extended family history assessment is recommended, and genetic risk assessment and genetic testing with multigene panels is a process and should be personalized. The question and answer session was lively with discussion of cost as well as direct-to-consumer genetic testing.
Sonia Kupfer, MD, AGAF, is an associate professor in the section of gastroenterology, hepatology, and nutrition at the University of Chicago. She has no financial conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Gastroenterologists should be skilled in recognition of patients with inherited risk of colorectal neoplasia. Fay Kastrinos, MD, presented a 49-year-old female who had more than 10 cumulative adenomas and a cecal adenocarcinoma on two colonoscopies, the first of which was performed for evaluation of rectal bleeding. Carol Burke, MD, reviewed the differential diagnosis of adenomatous polyposis (defined as >10 cumulative adenomas).
Germline syndromes include familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and a number of rare germline syndromes. Lynch syndrome should be considered especially for carriers of pathogenic variants in MSH6 who can present with a polyposis phenotype, as well as in children with constitutional mismatch repair deficiency syndrome. Finally, polyposis can be due to smoking, familial clustering, or previous abdominal radiation called therapy-associated polyposis. Polyposis without a known cause is referred to as colonic polyposis of unknown etiology (CPUE).
Dr. Kastrinos reviewed the patient’s three-generation family history of a brother and mother with “polyps” and second-degree relatives with endometrial and colon cancer. Niloy Jewel Samadder, MD, presented on the role of taking a comprehensive family history, tumor tests for Lynch syndrome, selection of genetic test type, and risks, benefits, and alternatives of genetic testing. Dr. Samadder reviewed indications for germline genetic testing for colorectal neoplasia of which the patient met two criteria, namely colorectal cancer under age 50 and 10 or more cumulative adenomas.
The final section was presented by this author on multigene panel testing, in which multiple genes are sequenced simultaneously. This patient’s panel showed two pathogenic variants in the MUTYH gene consistent with MAP, a recessive polyposis syndrome typically with 10s-100 cumulative adenomas. The test also showed a variant of uncertain significance (VUS) which is not clinically actionable. Providers counseling patients on multigene panel testing should discuss the possibility of VUS results (especially in individuals of non-European descent), moderate penetrant genes for which management recommendations are uncertain, or unexpected findings in genes not associated with colonic neoplasia. Studies have shown that the prevalence of finding an inherited syndrome is increased at younger ages of disease onset.
Dr. Kastrinos summarized key points from the session, including hereditary colorectal cancer syndromes are not rare, red flags for inherited syndromes, include early onset colorectal neoplasia and/or numerous relatives with colorectal and other extra-colonic cancer, extended family history assessment is recommended, and genetic risk assessment and genetic testing with multigene panels is a process and should be personalized. The question and answer session was lively with discussion of cost as well as direct-to-consumer genetic testing.
Sonia Kupfer, MD, AGAF, is an associate professor in the section of gastroenterology, hepatology, and nutrition at the University of Chicago. She has no financial conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Gastroenterologists should be skilled in recognition of patients with inherited risk of colorectal neoplasia. Fay Kastrinos, MD, presented a 49-year-old female who had more than 10 cumulative adenomas and a cecal adenocarcinoma on two colonoscopies, the first of which was performed for evaluation of rectal bleeding. Carol Burke, MD, reviewed the differential diagnosis of adenomatous polyposis (defined as >10 cumulative adenomas).
Germline syndromes include familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and a number of rare germline syndromes. Lynch syndrome should be considered especially for carriers of pathogenic variants in MSH6 who can present with a polyposis phenotype, as well as in children with constitutional mismatch repair deficiency syndrome. Finally, polyposis can be due to smoking, familial clustering, or previous abdominal radiation called therapy-associated polyposis. Polyposis without a known cause is referred to as colonic polyposis of unknown etiology (CPUE).
Dr. Kastrinos reviewed the patient’s three-generation family history of a brother and mother with “polyps” and second-degree relatives with endometrial and colon cancer. Niloy Jewel Samadder, MD, presented on the role of taking a comprehensive family history, tumor tests for Lynch syndrome, selection of genetic test type, and risks, benefits, and alternatives of genetic testing. Dr. Samadder reviewed indications for germline genetic testing for colorectal neoplasia of which the patient met two criteria, namely colorectal cancer under age 50 and 10 or more cumulative adenomas.
The final section was presented by this author on multigene panel testing, in which multiple genes are sequenced simultaneously. This patient’s panel showed two pathogenic variants in the MUTYH gene consistent with MAP, a recessive polyposis syndrome typically with 10s-100 cumulative adenomas. The test also showed a variant of uncertain significance (VUS) which is not clinically actionable. Providers counseling patients on multigene panel testing should discuss the possibility of VUS results (especially in individuals of non-European descent), moderate penetrant genes for which management recommendations are uncertain, or unexpected findings in genes not associated with colonic neoplasia. Studies have shown that the prevalence of finding an inherited syndrome is increased at younger ages of disease onset.
Dr. Kastrinos summarized key points from the session, including hereditary colorectal cancer syndromes are not rare, red flags for inherited syndromes, include early onset colorectal neoplasia and/or numerous relatives with colorectal and other extra-colonic cancer, extended family history assessment is recommended, and genetic risk assessment and genetic testing with multigene panels is a process and should be personalized. The question and answer session was lively with discussion of cost as well as direct-to-consumer genetic testing.
Sonia Kupfer, MD, AGAF, is an associate professor in the section of gastroenterology, hepatology, and nutrition at the University of Chicago. She has no financial conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Extraesophageal symptoms of GERD
Patients often present with symptoms that are not classic for reflux such as chronic cough, worsening asthma, sore throat, or globus.
In the upper GI section of the postgraduate course program, Rena Yadlapati, MD, and C. Prakash Gyawali, MD, MRCP, educated us about optimal strategies for diagnosis and treatment of this difficult group of patients. Dr. Gyawali reminded us of risk stratification of patients into those with high or low likelihood of reflux as contributing etiology for patients with suspected extraesophageal reflux. Dr. Yadlapti reviewed the utility of the HASBEER score in stratifying patients into these two risk categories. Patients with known reflux at baseline and/or if they have classic symptoms of reflux in addition to extraesophageal symptoms may be at higher likelihood of having abnormal esophageal acid exposure than those without classic heartburn and/or regurgitation. The low-risk group may then benefit from diagnostic testing off PPI therapy (either impedance/pH monitoring or wireless pH testing), whereas those in the high-risk group for reflux may undergo impedance pH testing on PPI therapy to ensure control of reflux while on therapy.
Dr. Yadlapati also updated the audience about lack of robust data to suggest clinical utility for oropharyngeal pH test or salivary pepsin assay testing. It was generally agreed on that the majority of patients who do not respond to aggressive acid suppressive therapy likely do not have reflux related extraesophageal symptoms and alternative etiologies may be at play.
Finally, both investigators outlined the importance of neuromodulation in those whose symptoms may be due to “irritable larynx.” They emphasized the role of tricyclics as well as gabapentin as off label uses for patients who have normal reflux testing and continue to have chronic cough or globus sensation.
Michael F. Vaezi, MD, PhD, MSc, is an associate chief and a clinical director of the division of gastroenterology, hepatology, and nutrition and director of the Clinical Research and Center for Esophageal Disorders at Vanderbilt University, Nashville, Tenn. He reports consulting for Phathom, Ironwood, Diversatek, Isothrive, and Medtronic. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Patients often present with symptoms that are not classic for reflux such as chronic cough, worsening asthma, sore throat, or globus.
In the upper GI section of the postgraduate course program, Rena Yadlapati, MD, and C. Prakash Gyawali, MD, MRCP, educated us about optimal strategies for diagnosis and treatment of this difficult group of patients. Dr. Gyawali reminded us of risk stratification of patients into those with high or low likelihood of reflux as contributing etiology for patients with suspected extraesophageal reflux. Dr. Yadlapti reviewed the utility of the HASBEER score in stratifying patients into these two risk categories. Patients with known reflux at baseline and/or if they have classic symptoms of reflux in addition to extraesophageal symptoms may be at higher likelihood of having abnormal esophageal acid exposure than those without classic heartburn and/or regurgitation. The low-risk group may then benefit from diagnostic testing off PPI therapy (either impedance/pH monitoring or wireless pH testing), whereas those in the high-risk group for reflux may undergo impedance pH testing on PPI therapy to ensure control of reflux while on therapy.
Dr. Yadlapati also updated the audience about lack of robust data to suggest clinical utility for oropharyngeal pH test or salivary pepsin assay testing. It was generally agreed on that the majority of patients who do not respond to aggressive acid suppressive therapy likely do not have reflux related extraesophageal symptoms and alternative etiologies may be at play.
Finally, both investigators outlined the importance of neuromodulation in those whose symptoms may be due to “irritable larynx.” They emphasized the role of tricyclics as well as gabapentin as off label uses for patients who have normal reflux testing and continue to have chronic cough or globus sensation.
Michael F. Vaezi, MD, PhD, MSc, is an associate chief and a clinical director of the division of gastroenterology, hepatology, and nutrition and director of the Clinical Research and Center for Esophageal Disorders at Vanderbilt University, Nashville, Tenn. He reports consulting for Phathom, Ironwood, Diversatek, Isothrive, and Medtronic. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Patients often present with symptoms that are not classic for reflux such as chronic cough, worsening asthma, sore throat, or globus.
In the upper GI section of the postgraduate course program, Rena Yadlapati, MD, and C. Prakash Gyawali, MD, MRCP, educated us about optimal strategies for diagnosis and treatment of this difficult group of patients. Dr. Gyawali reminded us of risk stratification of patients into those with high or low likelihood of reflux as contributing etiology for patients with suspected extraesophageal reflux. Dr. Yadlapti reviewed the utility of the HASBEER score in stratifying patients into these two risk categories. Patients with known reflux at baseline and/or if they have classic symptoms of reflux in addition to extraesophageal symptoms may be at higher likelihood of having abnormal esophageal acid exposure than those without classic heartburn and/or regurgitation. The low-risk group may then benefit from diagnostic testing off PPI therapy (either impedance/pH monitoring or wireless pH testing), whereas those in the high-risk group for reflux may undergo impedance pH testing on PPI therapy to ensure control of reflux while on therapy.
Dr. Yadlapati also updated the audience about lack of robust data to suggest clinical utility for oropharyngeal pH test or salivary pepsin assay testing. It was generally agreed on that the majority of patients who do not respond to aggressive acid suppressive therapy likely do not have reflux related extraesophageal symptoms and alternative etiologies may be at play.
Finally, both investigators outlined the importance of neuromodulation in those whose symptoms may be due to “irritable larynx.” They emphasized the role of tricyclics as well as gabapentin as off label uses for patients who have normal reflux testing and continue to have chronic cough or globus sensation.
Michael F. Vaezi, MD, PhD, MSc, is an associate chief and a clinical director of the division of gastroenterology, hepatology, and nutrition and director of the Clinical Research and Center for Esophageal Disorders at Vanderbilt University, Nashville, Tenn. He reports consulting for Phathom, Ironwood, Diversatek, Isothrive, and Medtronic. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Could the osteoporosis drug alendronate ward off diabetes?
A nationwide, retrospective, case-control study of older adults in Denmark suggests that the bisphosphonate alendronate that is widely used to treat osteoporosis may protect against new-onset type 2 diabetes. But these preliminary findings need to be confirmed in a randomized controlled trial, experts said.
The registry study showed that from 2008 to 2018, among individuals in Denmark age 50 and older (with a mean age of 67), those who were taking alendronate were 36% less likely to have new-onset type 2 diabetes than age- and sex-matched individuals who were not taking the drug, after controlling for multiple risk factors.
The results also suggest that longer alendronate use and higher compliance might be more protective.
Rikke Viggers, MD, a PhD student in the department of clinical medicine, Aalborg (Denmark) University, presented the findings during an oral session at the annual meeting of the European Association for the Study of Diabetes.
“Excitingly, our research suggests that alendronate, an inexpensive medicine widely used to treat osteoporosis, may also protect against type 2 diabetes,” Dr. Viggers summarized in a press release issued by the EASD.
“Type 2 diabetes is a serious lifelong condition that can lead to other serious health issues such as stroke, heart disease, blindness, and limb amputation,” she noted, “and anything that prevents or even delays it will also reduce a person’s risk of all these other conditions.”
“We believe that doctors should consider this when prescribing osteoporosis drugs to those with prediabetes or at high risk of type 2 diabetes,” she added.
Preliminary results, need for RCT
However, these are preliminary results, Dr. Viggers cautioned during the oral presentation and in an email. “This is a registry-based study,” she stressed, “and we cannot conclude causality.”
“We do not know if this effect [of decreased risk of developing diabetes among people taking alendronate] is ‘real’ and what the mechanisms are.”
“It could be a direct effect on peripheral tissues, for example, muscle and adipose tissue,” Dr. Viggers speculated, “or an indirect effect through bone metabolites that may impact glucose metabolism.”
The group is now conducting a randomized controlled trial in patients with diabetes and osteopenia or osteoporosis to examine the relationship between alendronate and insulin sensitivity, bone indices, and glycemic control.
They also aim to investigate whether alendronate is the optimal antiosteoporotic therapy for patients with type 2 diabetes. Preliminary results suggest that other bisphosphonates have similar effects.
“Alendronate decreases bone turnover and may not be beneficial in healthy bones,” Dr. Viggers noted. “However, as far as I know, potential other side effects have not been tested in healthy bones,” so further research is needed.
Invited to comment, Charles P. Vega, MD, who presented a case and a crowd-sourced opinion about deprescribing bisphosphonates, noted that type 2 diabetes is most often diagnosed between age 40 and 60, although a few cases are diagnosed after age 65, and the study by Dr. Viggers and colleagues suggests that alendronate might help lower the risk of diabetes onset in these older adults.
“This is an interesting retrospective analysis,” said Dr. Vega, health sciences clinical professor, family medicine, University of California, Irvine, but like the study authors, he cautioned that “it should be verified with other data.”
“A meta-analysis from clinical trials of bisphosphonates which followed blood glucose levels would be helpful,” he said.
Current registry study findings
Glucose homeostasis has been linked to bone metabolism, Dr. Viggers said, and bisphosphonates were associated with increased insulin sensitivity and decreased risk of diabetes risk in two registry studies from Denmark and Taiwan.
The researchers aimed to investigate if the risk of developing type 2 diabetes was altered by previous use of alendronate.
Using data from the national Danish Patient Registry, they identified 163,588 individuals age 50 and older newly diagnosed with type 2 diabetes in 2008-2018.
They matched each patient with three individuals of the same gender and age range who did not have diabetes, for a total of 490,764 controls.
Roughly two-thirds of participants were in their 50s or 60s, a quarter were in their 70s, and 10% were 80 or older. About half of participants were women (45%).
Compared to the patients with new-onset type 2 diabetes, the control participants were healthier: they were less likely to have obesity (6% vs. 17%) and had a lower mean Charlson Comorbidity Index (0.38 vs. 0.88).
Using data from the national Danish Health Service Prescription Registry, the researchers identified individuals who filled prescriptions for alendronate in 2008-2018.
After controlling for heavy smoking, alcohol abuse, obesity, pancreatitis, hyperthyroidism, hypothyroidism, glucocorticoid use, marital status, household income, and Charlson Comorbidity Index, people taking alendronate were less likely to have new-onset diabetes than those not taking this drug (odds ratio, 0.64; 95% confidence interval, 0.62-0.66).
The odds of developing type 2 diabetes were even lower among those who took alendronate for 8 years or more versus never-users (OR, 0.47; 95% CI, 0.40-0.56), after controlling for the same variables.
Session Chair Zhila Semnani-Azad, a PhD student in nutritional science, University of Toronto, wanted to know if the researchers accounted for physical activity and vitamin D use. Dr. Viggers replied that the registries did not have this information.
The study was funded by a Steno Collaborative Project grant from the Novo Nordisk Foundation, Denmark. Dr. Viggers has disclosed receiving a grant from the foundation. Dr. Vega has disclosed serving as a consultant for Johnson & Johnson.
A version of this article first appeared on Medscape.com.
A nationwide, retrospective, case-control study of older adults in Denmark suggests that the bisphosphonate alendronate that is widely used to treat osteoporosis may protect against new-onset type 2 diabetes. But these preliminary findings need to be confirmed in a randomized controlled trial, experts said.
The registry study showed that from 2008 to 2018, among individuals in Denmark age 50 and older (with a mean age of 67), those who were taking alendronate were 36% less likely to have new-onset type 2 diabetes than age- and sex-matched individuals who were not taking the drug, after controlling for multiple risk factors.
The results also suggest that longer alendronate use and higher compliance might be more protective.
Rikke Viggers, MD, a PhD student in the department of clinical medicine, Aalborg (Denmark) University, presented the findings during an oral session at the annual meeting of the European Association for the Study of Diabetes.
“Excitingly, our research suggests that alendronate, an inexpensive medicine widely used to treat osteoporosis, may also protect against type 2 diabetes,” Dr. Viggers summarized in a press release issued by the EASD.
“Type 2 diabetes is a serious lifelong condition that can lead to other serious health issues such as stroke, heart disease, blindness, and limb amputation,” she noted, “and anything that prevents or even delays it will also reduce a person’s risk of all these other conditions.”
“We believe that doctors should consider this when prescribing osteoporosis drugs to those with prediabetes or at high risk of type 2 diabetes,” she added.
Preliminary results, need for RCT
However, these are preliminary results, Dr. Viggers cautioned during the oral presentation and in an email. “This is a registry-based study,” she stressed, “and we cannot conclude causality.”
“We do not know if this effect [of decreased risk of developing diabetes among people taking alendronate] is ‘real’ and what the mechanisms are.”
“It could be a direct effect on peripheral tissues, for example, muscle and adipose tissue,” Dr. Viggers speculated, “or an indirect effect through bone metabolites that may impact glucose metabolism.”
The group is now conducting a randomized controlled trial in patients with diabetes and osteopenia or osteoporosis to examine the relationship between alendronate and insulin sensitivity, bone indices, and glycemic control.
They also aim to investigate whether alendronate is the optimal antiosteoporotic therapy for patients with type 2 diabetes. Preliminary results suggest that other bisphosphonates have similar effects.
“Alendronate decreases bone turnover and may not be beneficial in healthy bones,” Dr. Viggers noted. “However, as far as I know, potential other side effects have not been tested in healthy bones,” so further research is needed.
Invited to comment, Charles P. Vega, MD, who presented a case and a crowd-sourced opinion about deprescribing bisphosphonates, noted that type 2 diabetes is most often diagnosed between age 40 and 60, although a few cases are diagnosed after age 65, and the study by Dr. Viggers and colleagues suggests that alendronate might help lower the risk of diabetes onset in these older adults.
“This is an interesting retrospective analysis,” said Dr. Vega, health sciences clinical professor, family medicine, University of California, Irvine, but like the study authors, he cautioned that “it should be verified with other data.”
“A meta-analysis from clinical trials of bisphosphonates which followed blood glucose levels would be helpful,” he said.
Current registry study findings
Glucose homeostasis has been linked to bone metabolism, Dr. Viggers said, and bisphosphonates were associated with increased insulin sensitivity and decreased risk of diabetes risk in two registry studies from Denmark and Taiwan.
The researchers aimed to investigate if the risk of developing type 2 diabetes was altered by previous use of alendronate.
Using data from the national Danish Patient Registry, they identified 163,588 individuals age 50 and older newly diagnosed with type 2 diabetes in 2008-2018.
They matched each patient with three individuals of the same gender and age range who did not have diabetes, for a total of 490,764 controls.
Roughly two-thirds of participants were in their 50s or 60s, a quarter were in their 70s, and 10% were 80 or older. About half of participants were women (45%).
Compared to the patients with new-onset type 2 diabetes, the control participants were healthier: they were less likely to have obesity (6% vs. 17%) and had a lower mean Charlson Comorbidity Index (0.38 vs. 0.88).
Using data from the national Danish Health Service Prescription Registry, the researchers identified individuals who filled prescriptions for alendronate in 2008-2018.
After controlling for heavy smoking, alcohol abuse, obesity, pancreatitis, hyperthyroidism, hypothyroidism, glucocorticoid use, marital status, household income, and Charlson Comorbidity Index, people taking alendronate were less likely to have new-onset diabetes than those not taking this drug (odds ratio, 0.64; 95% confidence interval, 0.62-0.66).
The odds of developing type 2 diabetes were even lower among those who took alendronate for 8 years or more versus never-users (OR, 0.47; 95% CI, 0.40-0.56), after controlling for the same variables.
Session Chair Zhila Semnani-Azad, a PhD student in nutritional science, University of Toronto, wanted to know if the researchers accounted for physical activity and vitamin D use. Dr. Viggers replied that the registries did not have this information.
The study was funded by a Steno Collaborative Project grant from the Novo Nordisk Foundation, Denmark. Dr. Viggers has disclosed receiving a grant from the foundation. Dr. Vega has disclosed serving as a consultant for Johnson & Johnson.
A version of this article first appeared on Medscape.com.
A nationwide, retrospective, case-control study of older adults in Denmark suggests that the bisphosphonate alendronate that is widely used to treat osteoporosis may protect against new-onset type 2 diabetes. But these preliminary findings need to be confirmed in a randomized controlled trial, experts said.
The registry study showed that from 2008 to 2018, among individuals in Denmark age 50 and older (with a mean age of 67), those who were taking alendronate were 36% less likely to have new-onset type 2 diabetes than age- and sex-matched individuals who were not taking the drug, after controlling for multiple risk factors.
The results also suggest that longer alendronate use and higher compliance might be more protective.
Rikke Viggers, MD, a PhD student in the department of clinical medicine, Aalborg (Denmark) University, presented the findings during an oral session at the annual meeting of the European Association for the Study of Diabetes.
“Excitingly, our research suggests that alendronate, an inexpensive medicine widely used to treat osteoporosis, may also protect against type 2 diabetes,” Dr. Viggers summarized in a press release issued by the EASD.
“Type 2 diabetes is a serious lifelong condition that can lead to other serious health issues such as stroke, heart disease, blindness, and limb amputation,” she noted, “and anything that prevents or even delays it will also reduce a person’s risk of all these other conditions.”
“We believe that doctors should consider this when prescribing osteoporosis drugs to those with prediabetes or at high risk of type 2 diabetes,” she added.
Preliminary results, need for RCT
However, these are preliminary results, Dr. Viggers cautioned during the oral presentation and in an email. “This is a registry-based study,” she stressed, “and we cannot conclude causality.”
“We do not know if this effect [of decreased risk of developing diabetes among people taking alendronate] is ‘real’ and what the mechanisms are.”
“It could be a direct effect on peripheral tissues, for example, muscle and adipose tissue,” Dr. Viggers speculated, “or an indirect effect through bone metabolites that may impact glucose metabolism.”
The group is now conducting a randomized controlled trial in patients with diabetes and osteopenia or osteoporosis to examine the relationship between alendronate and insulin sensitivity, bone indices, and glycemic control.
They also aim to investigate whether alendronate is the optimal antiosteoporotic therapy for patients with type 2 diabetes. Preliminary results suggest that other bisphosphonates have similar effects.
“Alendronate decreases bone turnover and may not be beneficial in healthy bones,” Dr. Viggers noted. “However, as far as I know, potential other side effects have not been tested in healthy bones,” so further research is needed.
Invited to comment, Charles P. Vega, MD, who presented a case and a crowd-sourced opinion about deprescribing bisphosphonates, noted that type 2 diabetes is most often diagnosed between age 40 and 60, although a few cases are diagnosed after age 65, and the study by Dr. Viggers and colleagues suggests that alendronate might help lower the risk of diabetes onset in these older adults.
“This is an interesting retrospective analysis,” said Dr. Vega, health sciences clinical professor, family medicine, University of California, Irvine, but like the study authors, he cautioned that “it should be verified with other data.”
“A meta-analysis from clinical trials of bisphosphonates which followed blood glucose levels would be helpful,” he said.
Current registry study findings
Glucose homeostasis has been linked to bone metabolism, Dr. Viggers said, and bisphosphonates were associated with increased insulin sensitivity and decreased risk of diabetes risk in two registry studies from Denmark and Taiwan.
The researchers aimed to investigate if the risk of developing type 2 diabetes was altered by previous use of alendronate.
Using data from the national Danish Patient Registry, they identified 163,588 individuals age 50 and older newly diagnosed with type 2 diabetes in 2008-2018.
They matched each patient with three individuals of the same gender and age range who did not have diabetes, for a total of 490,764 controls.
Roughly two-thirds of participants were in their 50s or 60s, a quarter were in their 70s, and 10% were 80 or older. About half of participants were women (45%).
Compared to the patients with new-onset type 2 diabetes, the control participants were healthier: they were less likely to have obesity (6% vs. 17%) and had a lower mean Charlson Comorbidity Index (0.38 vs. 0.88).
Using data from the national Danish Health Service Prescription Registry, the researchers identified individuals who filled prescriptions for alendronate in 2008-2018.
After controlling for heavy smoking, alcohol abuse, obesity, pancreatitis, hyperthyroidism, hypothyroidism, glucocorticoid use, marital status, household income, and Charlson Comorbidity Index, people taking alendronate were less likely to have new-onset diabetes than those not taking this drug (odds ratio, 0.64; 95% confidence interval, 0.62-0.66).
The odds of developing type 2 diabetes were even lower among those who took alendronate for 8 years or more versus never-users (OR, 0.47; 95% CI, 0.40-0.56), after controlling for the same variables.
Session Chair Zhila Semnani-Azad, a PhD student in nutritional science, University of Toronto, wanted to know if the researchers accounted for physical activity and vitamin D use. Dr. Viggers replied that the registries did not have this information.
The study was funded by a Steno Collaborative Project grant from the Novo Nordisk Foundation, Denmark. Dr. Viggers has disclosed receiving a grant from the foundation. Dr. Vega has disclosed serving as a consultant for Johnson & Johnson.
A version of this article first appeared on Medscape.com.
FROM EASD 2021
Military sexual trauma tied to risk for hypertension
a new study suggests.
“Understanding a patient’s trauma history is invaluable for treating the whole person,” Allison E. Gaffey, PhD, Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, told this news organization.
“Assessing men and women’s history of trauma, including sexual trauma, is critical for recognizing nontraditional factors that contribute to their cardiovascular risk and to gain a more comprehensive understanding of their mental and physical health,” Dr. Gaffey added.
She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Lasting impact on physical health
Dr. Gaffey and colleagues analyzed data from the VA for roughly 1.2 million veterans (mean age, 30.2 years; 12% female) who were discharged from the military after Sept. 30, 2001, and who received health care services at VA medical centers from 2001 to 2017.
All were screened for sexual harassment and assault, known as military sexual trauma (MST), when they first began receiving VA care.
During 16 years of follow-up, 33,881 veterans screened positive for MST (65% women), and 307,332 developed hypertension (15% women).
Overall, MST was associated with a 30% increase in risk for incident hypertension in unadjusted models (hazard ratio, 1.30; 95% confidence interval, 1.28-1.33; P < .001).
After adjustment for demographic characteristics, lifestyle factors, cardiovascular comorbidities, PTSD, anxiety, and depression, MST remained significantly associated with hypertension (adjusted HR, 1.10; 95% CI, 1.08-1.12; P < .001).
When women and men were examined separately, the link between MST and risk for hypertension remained for both groups, but was slightly stronger among women.
“Sexual trauma has been associated with autonomic dysfunction, inflammation, and dysregulation in the hypothalamic pituitary adrenal axis and renin-angiotensin-aldosterone system, which could lead to elevations in BP over time,” Dr. Gaffey told this news organization.
“These findings show that even many years after being discharged from military service, exposure to military sexual trauma can continue to significantly influence veterans’ physical health,” she added.
Dr. Gaffey said it will be important to determine if early treatment of MST improves hypertension risk, particularly among those showing elevated blood pressure or stage 1 hypertension.
Social determinants of health
Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee, said the findings in this study are “in line with what we know about the impact of social determinants of health on high blood pressure.”
“There are studies that suggest that things that we historically don’t look at as risk factors for hypertension – lifelong racism, crime, mental health status – do in fact predict your risk of developing hypertension,” Dr. Lawrence, from Spectrum Health in Benton Harbor, Mich., told this news organization.
“It’s not just your genetics that will determine your health, and there are a lot of things that will affect your blood pressure. Your blood pressure is really just a barometer of everything that’s going on in your life and some of the things that have gone on in your life in the past,” added Dr. Lawrence, who wasn’t involved in the study.
Funding for the study was provided by the Department of Veterans Affairs. Dr. Gaffey and Dr. Lawrence have no relevant disclosures.
A version of this article first appeared on Medscape.com.
a new study suggests.
“Understanding a patient’s trauma history is invaluable for treating the whole person,” Allison E. Gaffey, PhD, Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, told this news organization.
“Assessing men and women’s history of trauma, including sexual trauma, is critical for recognizing nontraditional factors that contribute to their cardiovascular risk and to gain a more comprehensive understanding of their mental and physical health,” Dr. Gaffey added.
She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Lasting impact on physical health
Dr. Gaffey and colleagues analyzed data from the VA for roughly 1.2 million veterans (mean age, 30.2 years; 12% female) who were discharged from the military after Sept. 30, 2001, and who received health care services at VA medical centers from 2001 to 2017.
All were screened for sexual harassment and assault, known as military sexual trauma (MST), when they first began receiving VA care.
During 16 years of follow-up, 33,881 veterans screened positive for MST (65% women), and 307,332 developed hypertension (15% women).
Overall, MST was associated with a 30% increase in risk for incident hypertension in unadjusted models (hazard ratio, 1.30; 95% confidence interval, 1.28-1.33; P < .001).
After adjustment for demographic characteristics, lifestyle factors, cardiovascular comorbidities, PTSD, anxiety, and depression, MST remained significantly associated with hypertension (adjusted HR, 1.10; 95% CI, 1.08-1.12; P < .001).
When women and men were examined separately, the link between MST and risk for hypertension remained for both groups, but was slightly stronger among women.
“Sexual trauma has been associated with autonomic dysfunction, inflammation, and dysregulation in the hypothalamic pituitary adrenal axis and renin-angiotensin-aldosterone system, which could lead to elevations in BP over time,” Dr. Gaffey told this news organization.
“These findings show that even many years after being discharged from military service, exposure to military sexual trauma can continue to significantly influence veterans’ physical health,” she added.
Dr. Gaffey said it will be important to determine if early treatment of MST improves hypertension risk, particularly among those showing elevated blood pressure or stage 1 hypertension.
Social determinants of health
Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee, said the findings in this study are “in line with what we know about the impact of social determinants of health on high blood pressure.”
“There are studies that suggest that things that we historically don’t look at as risk factors for hypertension – lifelong racism, crime, mental health status – do in fact predict your risk of developing hypertension,” Dr. Lawrence, from Spectrum Health in Benton Harbor, Mich., told this news organization.
“It’s not just your genetics that will determine your health, and there are a lot of things that will affect your blood pressure. Your blood pressure is really just a barometer of everything that’s going on in your life and some of the things that have gone on in your life in the past,” added Dr. Lawrence, who wasn’t involved in the study.
Funding for the study was provided by the Department of Veterans Affairs. Dr. Gaffey and Dr. Lawrence have no relevant disclosures.
A version of this article first appeared on Medscape.com.
a new study suggests.
“Understanding a patient’s trauma history is invaluable for treating the whole person,” Allison E. Gaffey, PhD, Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, told this news organization.
“Assessing men and women’s history of trauma, including sexual trauma, is critical for recognizing nontraditional factors that contribute to their cardiovascular risk and to gain a more comprehensive understanding of their mental and physical health,” Dr. Gaffey added.
She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Lasting impact on physical health
Dr. Gaffey and colleagues analyzed data from the VA for roughly 1.2 million veterans (mean age, 30.2 years; 12% female) who were discharged from the military after Sept. 30, 2001, and who received health care services at VA medical centers from 2001 to 2017.
All were screened for sexual harassment and assault, known as military sexual trauma (MST), when they first began receiving VA care.
During 16 years of follow-up, 33,881 veterans screened positive for MST (65% women), and 307,332 developed hypertension (15% women).
Overall, MST was associated with a 30% increase in risk for incident hypertension in unadjusted models (hazard ratio, 1.30; 95% confidence interval, 1.28-1.33; P < .001).
After adjustment for demographic characteristics, lifestyle factors, cardiovascular comorbidities, PTSD, anxiety, and depression, MST remained significantly associated with hypertension (adjusted HR, 1.10; 95% CI, 1.08-1.12; P < .001).
When women and men were examined separately, the link between MST and risk for hypertension remained for both groups, but was slightly stronger among women.
“Sexual trauma has been associated with autonomic dysfunction, inflammation, and dysregulation in the hypothalamic pituitary adrenal axis and renin-angiotensin-aldosterone system, which could lead to elevations in BP over time,” Dr. Gaffey told this news organization.
“These findings show that even many years after being discharged from military service, exposure to military sexual trauma can continue to significantly influence veterans’ physical health,” she added.
Dr. Gaffey said it will be important to determine if early treatment of MST improves hypertension risk, particularly among those showing elevated blood pressure or stage 1 hypertension.
Social determinants of health
Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee, said the findings in this study are “in line with what we know about the impact of social determinants of health on high blood pressure.”
“There are studies that suggest that things that we historically don’t look at as risk factors for hypertension – lifelong racism, crime, mental health status – do in fact predict your risk of developing hypertension,” Dr. Lawrence, from Spectrum Health in Benton Harbor, Mich., told this news organization.
“It’s not just your genetics that will determine your health, and there are a lot of things that will affect your blood pressure. Your blood pressure is really just a barometer of everything that’s going on in your life and some of the things that have gone on in your life in the past,” added Dr. Lawrence, who wasn’t involved in the study.
Funding for the study was provided by the Department of Veterans Affairs. Dr. Gaffey and Dr. Lawrence have no relevant disclosures.
A version of this article first appeared on Medscape.com.
Novel trastuzumab duocarmazine significantly improved survival in advanced HER2-positive breast cancer
Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.
Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.
While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.
“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”
Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
Two or more prior therapies for metastatic breast cancer
TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.
Longer PFS with trastuzumab duocarmazine
Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).
A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
Ocular toxicity
Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.
Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.
Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.
TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.
Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.
Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.
While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.
“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”
Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
Two or more prior therapies for metastatic breast cancer
TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.
Longer PFS with trastuzumab duocarmazine
Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).
A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
Ocular toxicity
Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.
Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.
Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.
TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.
Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.
Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.
While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.
“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”
Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
Two or more prior therapies for metastatic breast cancer
TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.
Longer PFS with trastuzumab duocarmazine
Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).
A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
Ocular toxicity
Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.
Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.
Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.
TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.
FROM ESMO 2021