Conference Coverage

Violin and viola players can pay a price for the music they create: Many suffer from skin irritation and inflammation where the instruments touch their necks and upper bodies. Now, a new literature review offers insight into this common condition, known as “fiddler’s neck.”

Hill Street Studios/Stone/Getty Images

“These skin conditions are disfiguring, and they also carry so much psychological burden. Not only are these patients under constant pressure to perform at their maximum at all times, it really is troublesome when there is a barrier between you and performing art that you absolutely love,” lead author Henry Lim, an osteopathic medical student at the University of North Texas Health Science Center at Fort Worth, said in an interview.

The results of the literature review were presented in a poster at the Inaugural Symposium for Inflammatory Skin Disease.

Mr. Lim, who has a special interest in skin, said his own musical experience inspired the research. “Throughout my experience as a violinist, I faced many dermatologic issues because of my violin, and it affected my performance,” he said. “As time went on, I recognized that many other stringed instrumentalists were dealing with similar issues but chose to live with it because it came with the territory.”

One physician told Mr. Lim that he needed to quit in order to permanently treat his skin problems. He didn’t accept this answer and instead launched the literature review with colleagues Marshall Hall, MPH, also an osteopathic medical student with an interest in dermatology, and Sajid Surve, DO, codirector of the UNT Texas Center for Performing Arts Health.

Mr. Lim and colleagues evaluated 23 articles, which included case studies and literature reviews, about dermatitis in violinists, violists, cellists, bassists, guitarists and harpists. “Stringed instrumentalists are the highest at-risk population compared to performers who play other types of instruments,” Mr. Lim said.

The poster he presented at the meeting largely focuses on fiddler’s neck, which he defined as “simply dermatitis related to friction and allergic irritation from playing violin or viola.” Many people, he noted, are allergic to nickel, and the bracket that secures the violin’s chin rest “most often contains nickel. Even a very small concentration of nickel can cause massive reactions, and we found that the C string of a viola – the thickest, lowest-sounding string – contains a nickel concentration of up to 37%.”

Gold-coated strings are an alternative option, he said, but they’re more expensive.

Stringed instrumentalists may also be allergic to rosin applied to “bow hairs,” which is the hair – typically from horses – that is used to string bows, also described in the poster. “We found that there is an overall common allergy to the main ingredient called colophony,” Mr. Lim said. The legendary violin maker Antonio Stradivari “was rumored to have used colophony and another irritating ingredient called propolis in the wood varnish of his instruments. Because he was such a great influence on the art of violin crafting, his technique is still used in the modern era, which may be another contributing factor to the allergic reactions seen in stringed instrumentalists.”

(In the poster, the authors refer to one of the articles in the review, which described a violin maker allergic to colophony and propolis, who was treated with cetirizine, mild corticosteroids, and avoidance.)

What should dermatologists know about skin conditions in these musicians? Mr. Hall, one of the coauthors of the report, suggested they invite the patients to play their instruments during a visit. “The musicians may not understand that they are doing certain things with their movements, but looking from a clinical lens, we are able to see how their biomechanics and posture [are] contributing to their dermatitis,” he said.

Dr. Surve, the other coauthor, also suggested speaking to the patient’s teacher, coach, or mentor. “Keeping that person in the loop regarding what you are seeing and recommending will go a long way towards helping your patient,” he said. “If the teacher doesn’t understand or agree with what you’re trying to accomplish, they may try to undermine your plan of care. But if they are on board, they become a valuable tool for facilitating and reinforcing it.”

As for treatments, avoidance of the instruments is the most effective, but is simply not feasible for many musicians. “Certain interventions like creating a barrier between the musician and the instrument can reduce the risk of contact dermatitis without compromising the quality [of playing] as much,” Mr. Hall said. The poster reported that a handkerchief was used for this purpose in one case attributed to nickel sulfate in a 16-year-old .

Purchasing more expensive instrument materials to prevent reactions is another option, he said, and players can also purchase stands. But musicians may be resistant to any treatment that changes how the instruments sound or forces them to adjust the way they do things, he cautioned.

No funding for the study or author disclosures were reported.

Violin and viola players can pay a price for the music they create: Many suffer from skin irritation and inflammation where the instruments touch their necks and upper bodies. Now, a new literature review offers insight into this common condition, known as “fiddler’s neck.”

Hill Street Studios/Stone/Getty Images

“These skin conditions are disfiguring, and they also carry so much psychological burden. Not only are these patients under constant pressure to perform at their maximum at all times, it really is troublesome when there is a barrier between you and performing art that you absolutely love,” lead author Henry Lim, an osteopathic medical student at the University of North Texas Health Science Center at Fort Worth, said in an interview.

The results of the literature review were presented in a poster at the Inaugural Symposium for Inflammatory Skin Disease.

Mr. Lim, who has a special interest in skin, said his own musical experience inspired the research. “Throughout my experience as a violinist, I faced many dermatologic issues because of my violin, and it affected my performance,” he said. “As time went on, I recognized that many other stringed instrumentalists were dealing with similar issues but chose to live with it because it came with the territory.”

One physician told Mr. Lim that he needed to quit in order to permanently treat his skin problems. He didn’t accept this answer and instead launched the literature review with colleagues Marshall Hall, MPH, also an osteopathic medical student with an interest in dermatology, and Sajid Surve, DO, codirector of the UNT Texas Center for Performing Arts Health.

Mr. Lim and colleagues evaluated 23 articles, which included case studies and literature reviews, about dermatitis in violinists, violists, cellists, bassists, guitarists and harpists. “Stringed instrumentalists are the highest at-risk population compared to performers who play other types of instruments,” Mr. Lim said.

The poster he presented at the meeting largely focuses on fiddler’s neck, which he defined as “simply dermatitis related to friction and allergic irritation from playing violin or viola.” Many people, he noted, are allergic to nickel, and the bracket that secures the violin’s chin rest “most often contains nickel. Even a very small concentration of nickel can cause massive reactions, and we found that the C string of a viola – the thickest, lowest-sounding string – contains a nickel concentration of up to 37%.”

Gold-coated strings are an alternative option, he said, but they’re more expensive.

Stringed instrumentalists may also be allergic to rosin applied to “bow hairs,” which is the hair – typically from horses – that is used to string bows, also described in the poster. “We found that there is an overall common allergy to the main ingredient called colophony,” Mr. Lim said. The legendary violin maker Antonio Stradivari “was rumored to have used colophony and another irritating ingredient called propolis in the wood varnish of his instruments. Because he was such a great influence on the art of violin crafting, his technique is still used in the modern era, which may be another contributing factor to the allergic reactions seen in stringed instrumentalists.”

(In the poster, the authors refer to one of the articles in the review, which described a violin maker allergic to colophony and propolis, who was treated with cetirizine, mild corticosteroids, and avoidance.)

What should dermatologists know about skin conditions in these musicians? Mr. Hall, one of the coauthors of the report, suggested they invite the patients to play their instruments during a visit. “The musicians may not understand that they are doing certain things with their movements, but looking from a clinical lens, we are able to see how their biomechanics and posture [are] contributing to their dermatitis,” he said.

Dr. Surve, the other coauthor, also suggested speaking to the patient’s teacher, coach, or mentor. “Keeping that person in the loop regarding what you are seeing and recommending will go a long way towards helping your patient,” he said. “If the teacher doesn’t understand or agree with what you’re trying to accomplish, they may try to undermine your plan of care. But if they are on board, they become a valuable tool for facilitating and reinforcing it.”

As for treatments, avoidance of the instruments is the most effective, but is simply not feasible for many musicians. “Certain interventions like creating a barrier between the musician and the instrument can reduce the risk of contact dermatitis without compromising the quality [of playing] as much,” Mr. Hall said. The poster reported that a handkerchief was used for this purpose in one case attributed to nickel sulfate in a 16-year-old .

Purchasing more expensive instrument materials to prevent reactions is another option, he said, and players can also purchase stands. But musicians may be resistant to any treatment that changes how the instruments sound or forces them to adjust the way they do things, he cautioned.

No funding for the study or author disclosures were reported.

Violin and viola players can pay a price for the music they create: Many suffer from skin irritation and inflammation where the instruments touch their necks and upper bodies. Now, a new literature review offers insight into this common condition, known as “fiddler’s neck.”

Hill Street Studios/Stone/Getty Images

“These skin conditions are disfiguring, and they also carry so much psychological burden. Not only are these patients under constant pressure to perform at their maximum at all times, it really is troublesome when there is a barrier between you and performing art that you absolutely love,” lead author Henry Lim, an osteopathic medical student at the University of North Texas Health Science Center at Fort Worth, said in an interview.

The results of the literature review were presented in a poster at the Inaugural Symposium for Inflammatory Skin Disease.

Mr. Lim, who has a special interest in skin, said his own musical experience inspired the research. “Throughout my experience as a violinist, I faced many dermatologic issues because of my violin, and it affected my performance,” he said. “As time went on, I recognized that many other stringed instrumentalists were dealing with similar issues but chose to live with it because it came with the territory.”

One physician told Mr. Lim that he needed to quit in order to permanently treat his skin problems. He didn’t accept this answer and instead launched the literature review with colleagues Marshall Hall, MPH, also an osteopathic medical student with an interest in dermatology, and Sajid Surve, DO, codirector of the UNT Texas Center for Performing Arts Health.

Mr. Lim and colleagues evaluated 23 articles, which included case studies and literature reviews, about dermatitis in violinists, violists, cellists, bassists, guitarists and harpists. “Stringed instrumentalists are the highest at-risk population compared to performers who play other types of instruments,” Mr. Lim said.

The poster he presented at the meeting largely focuses on fiddler’s neck, which he defined as “simply dermatitis related to friction and allergic irritation from playing violin or viola.” Many people, he noted, are allergic to nickel, and the bracket that secures the violin’s chin rest “most often contains nickel. Even a very small concentration of nickel can cause massive reactions, and we found that the C string of a viola – the thickest, lowest-sounding string – contains a nickel concentration of up to 37%.”

Gold-coated strings are an alternative option, he said, but they’re more expensive.

Stringed instrumentalists may also be allergic to rosin applied to “bow hairs,” which is the hair – typically from horses – that is used to string bows, also described in the poster. “We found that there is an overall common allergy to the main ingredient called colophony,” Mr. Lim said. The legendary violin maker Antonio Stradivari “was rumored to have used colophony and another irritating ingredient called propolis in the wood varnish of his instruments. Because he was such a great influence on the art of violin crafting, his technique is still used in the modern era, which may be another contributing factor to the allergic reactions seen in stringed instrumentalists.”

(In the poster, the authors refer to one of the articles in the review, which described a violin maker allergic to colophony and propolis, who was treated with cetirizine, mild corticosteroids, and avoidance.)

What should dermatologists know about skin conditions in these musicians? Mr. Hall, one of the coauthors of the report, suggested they invite the patients to play their instruments during a visit. “The musicians may not understand that they are doing certain things with their movements, but looking from a clinical lens, we are able to see how their biomechanics and posture [are] contributing to their dermatitis,” he said.

Dr. Surve, the other coauthor, also suggested speaking to the patient’s teacher, coach, or mentor. “Keeping that person in the loop regarding what you are seeing and recommending will go a long way towards helping your patient,” he said. “If the teacher doesn’t understand or agree with what you’re trying to accomplish, they may try to undermine your plan of care. But if they are on board, they become a valuable tool for facilitating and reinforcing it.”

As for treatments, avoidance of the instruments is the most effective, but is simply not feasible for many musicians. “Certain interventions like creating a barrier between the musician and the instrument can reduce the risk of contact dermatitis without compromising the quality [of playing] as much,” Mr. Hall said. The poster reported that a handkerchief was used for this purpose in one case attributed to nickel sulfate in a 16-year-old .

Purchasing more expensive instrument materials to prevent reactions is another option, he said, and players can also purchase stands. But musicians may be resistant to any treatment that changes how the instruments sound or forces them to adjust the way they do things, he cautioned.

No funding for the study or author disclosures were reported.

As physicians and patients anticipate the U.S. approval of oral Janus kinase 1/JAK2 inhibitors for atopic dermatitis (AD), how well they will work hinges on a host of factors, largely because of the heterogeneous nature of the disease.

“Atopic dermatitis patients have different complaints,” Jacob P. Thyssen, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Some of them have repeated infections. Some have psychiatric symptoms. Others have widespread eczema. When you talk about how well they work, it really depends on what aspects of AD, what subgroups of AD, and how well they work with comorbidities of AD.”

Baricitinib, a JAK1/JAK2 inhibitor in 2-mg and 4-mg tablets, is available in the European Union, and is under Food and Drug Administration review for AD in the United States. Two JAK1 inhibitors continue to be evaluated in AD clinical trials and are also under FDA review for AD: abrocitinib (100 mg and 200 mg) and upadacitinib (15 mg and 30 mg). None of these agents have been tested in head-to-head trials and only one (abrocitinib) has been compared with the interleukin-4 receptor–alpha antagonist dupilumab, which makes meaningful direct comparisons impossible. (Baricitinib and upadacitinib are approved for treating RA in the United States.)

In his informal assessment from clinical trial data of how these three JAK inhibitors compare with the biologic agents dupilumab and tralokinumab, with potency as an indication, Dr. Thyssen, professor of dermatology at the University of Copenhagen, observed that abrocitinib and dupilumab “are somewhere in the middle,” tralokinumab and baricitinib are “slightly weaker,” while upadacitinib is “very potent.” (Dupilumab is approved by the FDA for treating AD ages 6 and older, and tralokinumab, a fully human monoclonal antibody that binds to IL-13, is under FDA review for AD.)

However, he cautioned that making direct comparisons of these drugs is limited by differences in clinical trial designs, trial length, severity of disease at baseline, and demographics. “Placebo effects also differ between trials, and the speed of onset is different between JAK inhibitors and biologic agents. Because of this, efficacy can be difficult to assess over 12-16 weeks. That’s why long-term studies are necessary.”

It’s also tricky to compare safety signals with baricitinib, abrocitinib, and upadacitinib, “because some of them are JAK1 inhibitors; others are JAK1/JAK2 inhibitors,” he continued. “Even the molecules that inhibit JAK1 are different, so making a comparison between abrocitinib and upadacitinib requires studies that do this is in the best way and over a long period of time.”
 

Safety signals

Common safety signals in this drug class include nasopharyngitis, nausea, and headache. “Many of these are short lasting, meaning that patients will perhaps have a headache for a day or two and then it will be over,” said Dr. Thyssen, who is also a consultant dermatologist at Bispebjerg Hospital in Copenhagen. “This means that even though we see high proportions of safety signals, this is probably not going to limit the use of JAK inhibitors in most of our patients. Then we have an acne signal in higher proportions for abrocitinib and upadacitinib than for baricitinib, so perhaps this is related to the potency.”

There is also an increased risk for infections, including herpes zoster. “Is this a class effect?” he asked. “We see quite a bit for baricitinib, particularly when it’s used for rheumatoid arthritis. We also see it in AD patients, but we don’t know to what degree yet. We need the real-world evidence before we can make any conclusions.” Routine blood monitoring tests are also required in patients taking JAK inhibitors, because of the risk for leukopenia and effects on liver enzymes.

Then there’s the risk of deep vein thrombosis/pulmonary embolism. “This is mostly linked to baricitinib use, but is this a class effect or is it specific to baricitinib?” he asked. “We’ll have to wait and see, but I think overall, this is not something I have great fear of because we see that AD patients are young, usually with a normal [body mass index], at least in Europe. But we have to study this closely.”

From a clinical standpoint, JAK1/2 inhibitors work well on every measurable aspect of AD, he said, including eczema severity, itch, skin pain, sleep, and quality of life. “Based on conference abstracts and publications, they seem to work equally well independent of race, BMI, atopy status, age, and whether their AD is extrinsic or intrinsic,” Dr. Thyssen added. “One thing we haven’t learned from the companies is, what patients have the highest likelihood of getting a good treatment response? We don’t have good biomarkers yet, but anything the companies can do to help us identify the patients with the greatest chance of success would be so welcome.”

The best available data suggest that JAK inhibitors benefit AD patients with certain comorbidities, including inflammatory bowel disease (with upadacitinib), RA (with both baricitinib and upadacitinib), and alopecia areata (with baricitinib). “These drugs also have been shown to work well for the psychiatric symptoms of disease,” he said.

“As for patients with type 2 inflammation in the airways such as asthma and rhinitis, dupilumab works, but do the JAK inhibitors work? It’s possible from a mode of action standpoint, but we don’t know.” It also remains unclear how JAK inhibitors will fare in the treatment of chronic hand eczema and ocular surface disease, like allergic conjunctivitis, he said.

Despite the unknowns, Dr. Thyssen emphasized the promise that JAK inhibitors hold for AD patients. “We know they provide good AD control,” he said. “For some, like baricitinib, you may need to instruct the patient to use topical corticosteroids as well, but this does not seem to be necessary for upadacitinib and abrocitinib. You really have a single bullet here that will take away most of the problems for many patients, with very fast onset of action, which is important for our patients.”

Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.

dbrunk@mdedge.com

As physicians and patients anticipate the U.S. approval of oral Janus kinase 1/JAK2 inhibitors for atopic dermatitis (AD), how well they will work hinges on a host of factors, largely because of the heterogeneous nature of the disease.

“Atopic dermatitis patients have different complaints,” Jacob P. Thyssen, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Some of them have repeated infections. Some have psychiatric symptoms. Others have widespread eczema. When you talk about how well they work, it really depends on what aspects of AD, what subgroups of AD, and how well they work with comorbidities of AD.”

Baricitinib, a JAK1/JAK2 inhibitor in 2-mg and 4-mg tablets, is available in the European Union, and is under Food and Drug Administration review for AD in the United States. Two JAK1 inhibitors continue to be evaluated in AD clinical trials and are also under FDA review for AD: abrocitinib (100 mg and 200 mg) and upadacitinib (15 mg and 30 mg). None of these agents have been tested in head-to-head trials and only one (abrocitinib) has been compared with the interleukin-4 receptor–alpha antagonist dupilumab, which makes meaningful direct comparisons impossible. (Baricitinib and upadacitinib are approved for treating RA in the United States.)

In his informal assessment from clinical trial data of how these three JAK inhibitors compare with the biologic agents dupilumab and tralokinumab, with potency as an indication, Dr. Thyssen, professor of dermatology at the University of Copenhagen, observed that abrocitinib and dupilumab “are somewhere in the middle,” tralokinumab and baricitinib are “slightly weaker,” while upadacitinib is “very potent.” (Dupilumab is approved by the FDA for treating AD ages 6 and older, and tralokinumab, a fully human monoclonal antibody that binds to IL-13, is under FDA review for AD.)

However, he cautioned that making direct comparisons of these drugs is limited by differences in clinical trial designs, trial length, severity of disease at baseline, and demographics. “Placebo effects also differ between trials, and the speed of onset is different between JAK inhibitors and biologic agents. Because of this, efficacy can be difficult to assess over 12-16 weeks. That’s why long-term studies are necessary.”

It’s also tricky to compare safety signals with baricitinib, abrocitinib, and upadacitinib, “because some of them are JAK1 inhibitors; others are JAK1/JAK2 inhibitors,” he continued. “Even the molecules that inhibit JAK1 are different, so making a comparison between abrocitinib and upadacitinib requires studies that do this is in the best way and over a long period of time.”
 

Safety signals

Common safety signals in this drug class include nasopharyngitis, nausea, and headache. “Many of these are short lasting, meaning that patients will perhaps have a headache for a day or two and then it will be over,” said Dr. Thyssen, who is also a consultant dermatologist at Bispebjerg Hospital in Copenhagen. “This means that even though we see high proportions of safety signals, this is probably not going to limit the use of JAK inhibitors in most of our patients. Then we have an acne signal in higher proportions for abrocitinib and upadacitinib than for baricitinib, so perhaps this is related to the potency.”

There is also an increased risk for infections, including herpes zoster. “Is this a class effect?” he asked. “We see quite a bit for baricitinib, particularly when it’s used for rheumatoid arthritis. We also see it in AD patients, but we don’t know to what degree yet. We need the real-world evidence before we can make any conclusions.” Routine blood monitoring tests are also required in patients taking JAK inhibitors, because of the risk for leukopenia and effects on liver enzymes.

Then there’s the risk of deep vein thrombosis/pulmonary embolism. “This is mostly linked to baricitinib use, but is this a class effect or is it specific to baricitinib?” he asked. “We’ll have to wait and see, but I think overall, this is not something I have great fear of because we see that AD patients are young, usually with a normal [body mass index], at least in Europe. But we have to study this closely.”

From a clinical standpoint, JAK1/2 inhibitors work well on every measurable aspect of AD, he said, including eczema severity, itch, skin pain, sleep, and quality of life. “Based on conference abstracts and publications, they seem to work equally well independent of race, BMI, atopy status, age, and whether their AD is extrinsic or intrinsic,” Dr. Thyssen added. “One thing we haven’t learned from the companies is, what patients have the highest likelihood of getting a good treatment response? We don’t have good biomarkers yet, but anything the companies can do to help us identify the patients with the greatest chance of success would be so welcome.”

The best available data suggest that JAK inhibitors benefit AD patients with certain comorbidities, including inflammatory bowel disease (with upadacitinib), RA (with both baricitinib and upadacitinib), and alopecia areata (with baricitinib). “These drugs also have been shown to work well for the psychiatric symptoms of disease,” he said.

“As for patients with type 2 inflammation in the airways such as asthma and rhinitis, dupilumab works, but do the JAK inhibitors work? It’s possible from a mode of action standpoint, but we don’t know.” It also remains unclear how JAK inhibitors will fare in the treatment of chronic hand eczema and ocular surface disease, like allergic conjunctivitis, he said.

Despite the unknowns, Dr. Thyssen emphasized the promise that JAK inhibitors hold for AD patients. “We know they provide good AD control,” he said. “For some, like baricitinib, you may need to instruct the patient to use topical corticosteroids as well, but this does not seem to be necessary for upadacitinib and abrocitinib. You really have a single bullet here that will take away most of the problems for many patients, with very fast onset of action, which is important for our patients.”

Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.

dbrunk@mdedge.com

As physicians and patients anticipate the U.S. approval of oral Janus kinase 1/JAK2 inhibitors for atopic dermatitis (AD), how well they will work hinges on a host of factors, largely because of the heterogeneous nature of the disease.

“Atopic dermatitis patients have different complaints,” Jacob P. Thyssen, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Some of them have repeated infections. Some have psychiatric symptoms. Others have widespread eczema. When you talk about how well they work, it really depends on what aspects of AD, what subgroups of AD, and how well they work with comorbidities of AD.”

Baricitinib, a JAK1/JAK2 inhibitor in 2-mg and 4-mg tablets, is available in the European Union, and is under Food and Drug Administration review for AD in the United States. Two JAK1 inhibitors continue to be evaluated in AD clinical trials and are also under FDA review for AD: abrocitinib (100 mg and 200 mg) and upadacitinib (15 mg and 30 mg). None of these agents have been tested in head-to-head trials and only one (abrocitinib) has been compared with the interleukin-4 receptor–alpha antagonist dupilumab, which makes meaningful direct comparisons impossible. (Baricitinib and upadacitinib are approved for treating RA in the United States.)

In his informal assessment from clinical trial data of how these three JAK inhibitors compare with the biologic agents dupilumab and tralokinumab, with potency as an indication, Dr. Thyssen, professor of dermatology at the University of Copenhagen, observed that abrocitinib and dupilumab “are somewhere in the middle,” tralokinumab and baricitinib are “slightly weaker,” while upadacitinib is “very potent.” (Dupilumab is approved by the FDA for treating AD ages 6 and older, and tralokinumab, a fully human monoclonal antibody that binds to IL-13, is under FDA review for AD.)

However, he cautioned that making direct comparisons of these drugs is limited by differences in clinical trial designs, trial length, severity of disease at baseline, and demographics. “Placebo effects also differ between trials, and the speed of onset is different between JAK inhibitors and biologic agents. Because of this, efficacy can be difficult to assess over 12-16 weeks. That’s why long-term studies are necessary.”

It’s also tricky to compare safety signals with baricitinib, abrocitinib, and upadacitinib, “because some of them are JAK1 inhibitors; others are JAK1/JAK2 inhibitors,” he continued. “Even the molecules that inhibit JAK1 are different, so making a comparison between abrocitinib and upadacitinib requires studies that do this is in the best way and over a long period of time.”
 

Safety signals

Common safety signals in this drug class include nasopharyngitis, nausea, and headache. “Many of these are short lasting, meaning that patients will perhaps have a headache for a day or two and then it will be over,” said Dr. Thyssen, who is also a consultant dermatologist at Bispebjerg Hospital in Copenhagen. “This means that even though we see high proportions of safety signals, this is probably not going to limit the use of JAK inhibitors in most of our patients. Then we have an acne signal in higher proportions for abrocitinib and upadacitinib than for baricitinib, so perhaps this is related to the potency.”

There is also an increased risk for infections, including herpes zoster. “Is this a class effect?” he asked. “We see quite a bit for baricitinib, particularly when it’s used for rheumatoid arthritis. We also see it in AD patients, but we don’t know to what degree yet. We need the real-world evidence before we can make any conclusions.” Routine blood monitoring tests are also required in patients taking JAK inhibitors, because of the risk for leukopenia and effects on liver enzymes.

Then there’s the risk of deep vein thrombosis/pulmonary embolism. “This is mostly linked to baricitinib use, but is this a class effect or is it specific to baricitinib?” he asked. “We’ll have to wait and see, but I think overall, this is not something I have great fear of because we see that AD patients are young, usually with a normal [body mass index], at least in Europe. But we have to study this closely.”

From a clinical standpoint, JAK1/2 inhibitors work well on every measurable aspect of AD, he said, including eczema severity, itch, skin pain, sleep, and quality of life. “Based on conference abstracts and publications, they seem to work equally well independent of race, BMI, atopy status, age, and whether their AD is extrinsic or intrinsic,” Dr. Thyssen added. “One thing we haven’t learned from the companies is, what patients have the highest likelihood of getting a good treatment response? We don’t have good biomarkers yet, but anything the companies can do to help us identify the patients with the greatest chance of success would be so welcome.”

The best available data suggest that JAK inhibitors benefit AD patients with certain comorbidities, including inflammatory bowel disease (with upadacitinib), RA (with both baricitinib and upadacitinib), and alopecia areata (with baricitinib). “These drugs also have been shown to work well for the psychiatric symptoms of disease,” he said.

“As for patients with type 2 inflammation in the airways such as asthma and rhinitis, dupilumab works, but do the JAK inhibitors work? It’s possible from a mode of action standpoint, but we don’t know.” It also remains unclear how JAK inhibitors will fare in the treatment of chronic hand eczema and ocular surface disease, like allergic conjunctivitis, he said.

Despite the unknowns, Dr. Thyssen emphasized the promise that JAK inhibitors hold for AD patients. “We know they provide good AD control,” he said. “For some, like baricitinib, you may need to instruct the patient to use topical corticosteroids as well, but this does not seem to be necessary for upadacitinib and abrocitinib. You really have a single bullet here that will take away most of the problems for many patients, with very fast onset of action, which is important for our patients.”

Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.

dbrunk@mdedge.com

Evaluation of a large insurance claims database has provided some insight into how ICD-10 indoor tanning codes are being used in practice, according to a study presented at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

“Since indoor tanning ICD-10 codes were only recently universally implemented in 2015, and providers may still be using other codes that cover similar services, we think our data likely underestimate the number of encounters and sequelae associated with indoor tanning,” Alexandria M. Brown, BSA, of Baylor College of Medicine, Houston, said in her presentation. “We think increased usage of these indoor tanning exposure codes in coming years will strengthen this body of indoor tanning literature and data.”

Using insurance claims data on about 43 million patients from Truven Health MarketScan, Ms. Brown and colleagues analyzed patient encounters with ICD-10 indoor tanning codes W89.1, W89.1XXA, W89.1XXD, and W89.1XXS between 2016 and 2018 for about 43 million patients. Overall, there were 4,550 patient encounters where these codes had been recorded, with most (99%) occurring in an outpatient setting. The majority of providers at these encounters were dermatologists (72%). Patients were mostly women (85%); and most were ages 25-34 years (19.4%), 35-44 years (20.6%), 45-54 years (22.7%), and 55-64 years (19%). Almost 5% were 65 and over, 11.7% were ages 18-24, and 1.6% were under age 18.

The use of indoor tanning codes were most common in the Midwest (55 per 100,000 encounters with dermatologists), compared with 16 per 100,000 in the Northeast, 21 per 100,000 in the West, and 28 per 100,000 in the South. CPT codes for “destruction of a premalignant lesion” and “biopsy” were the most frequently used codes entered at visits where indoor tanning codes were also entered, and were present in 15.1% of encounters and 18.4% of encounters, respectively.

“This suggests that many of these encounters may have been for skin cancer surveillance and that indoor tanning exposure may have been coded as part of a patient’s skin cancer risk profile,” Ms. Brown noted.

The study shows how these codes are being used and could help determine health care use patterns for these patients as well as their comorbidities, behaviors, and risk factors, according to the authors, who believe this is the first study to look at the use of ICD-10 indoor tanning codes.

“Any effort to reduce indoor tanning requires knowledge of the population at risk. It has been shown that the ability to recognize and provide counseling to at-risk patients can improve sun protective behaviors and reduce indoor tanning,” Ms. Brown said. Claims databases can be a “valuable tool to better understand patients who have been exposed to indoor tanning and their associated risk factors, comorbidities, behaviors, and health care utilization.”

In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said the study was interesting and “provides some guidance with respect to who, when, and where in the U.S. to target educational initiatives on the harms of tanning beds.”

Dr. Friedman, who was not involved with the research, agreed with the authors’ assertion that their study was underestimating the use of indoor tanning beds. “Using a large database provides the means to better generalize one’s dataset; however in this case, it relies on proper coding by the practitioner,” or even using the code for tanning bed use at all.

“There also could be some inherent bias given most of the cases for which the code was used was for skin cancer surveillance, and therefore tanning bed use was top of mind,” he said.

While he believes this study may not be most efficient way of determining demographics of at-risk individuals using tanning beds, Dr. Friedman said the results “should serve as the impetus to develop public health campaigns around this information, following which research can be conducted to evaluate if the intervention had an impact.”

Ms. Brown and Dr. Friedman reported no relevant financial disclosures.

Evaluation of a large insurance claims database has provided some insight into how ICD-10 indoor tanning codes are being used in practice, according to a study presented at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

“Since indoor tanning ICD-10 codes were only recently universally implemented in 2015, and providers may still be using other codes that cover similar services, we think our data likely underestimate the number of encounters and sequelae associated with indoor tanning,” Alexandria M. Brown, BSA, of Baylor College of Medicine, Houston, said in her presentation. “We think increased usage of these indoor tanning exposure codes in coming years will strengthen this body of indoor tanning literature and data.”

Using insurance claims data on about 43 million patients from Truven Health MarketScan, Ms. Brown and colleagues analyzed patient encounters with ICD-10 indoor tanning codes W89.1, W89.1XXA, W89.1XXD, and W89.1XXS between 2016 and 2018 for about 43 million patients. Overall, there were 4,550 patient encounters where these codes had been recorded, with most (99%) occurring in an outpatient setting. The majority of providers at these encounters were dermatologists (72%). Patients were mostly women (85%); and most were ages 25-34 years (19.4%), 35-44 years (20.6%), 45-54 years (22.7%), and 55-64 years (19%). Almost 5% were 65 and over, 11.7% were ages 18-24, and 1.6% were under age 18.

The use of indoor tanning codes were most common in the Midwest (55 per 100,000 encounters with dermatologists), compared with 16 per 100,000 in the Northeast, 21 per 100,000 in the West, and 28 per 100,000 in the South. CPT codes for “destruction of a premalignant lesion” and “biopsy” were the most frequently used codes entered at visits where indoor tanning codes were also entered, and were present in 15.1% of encounters and 18.4% of encounters, respectively.

“This suggests that many of these encounters may have been for skin cancer surveillance and that indoor tanning exposure may have been coded as part of a patient’s skin cancer risk profile,” Ms. Brown noted.

The study shows how these codes are being used and could help determine health care use patterns for these patients as well as their comorbidities, behaviors, and risk factors, according to the authors, who believe this is the first study to look at the use of ICD-10 indoor tanning codes.

“Any effort to reduce indoor tanning requires knowledge of the population at risk. It has been shown that the ability to recognize and provide counseling to at-risk patients can improve sun protective behaviors and reduce indoor tanning,” Ms. Brown said. Claims databases can be a “valuable tool to better understand patients who have been exposed to indoor tanning and their associated risk factors, comorbidities, behaviors, and health care utilization.”

In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said the study was interesting and “provides some guidance with respect to who, when, and where in the U.S. to target educational initiatives on the harms of tanning beds.”

Dr. Friedman, who was not involved with the research, agreed with the authors’ assertion that their study was underestimating the use of indoor tanning beds. “Using a large database provides the means to better generalize one’s dataset; however in this case, it relies on proper coding by the practitioner,” or even using the code for tanning bed use at all.

“There also could be some inherent bias given most of the cases for which the code was used was for skin cancer surveillance, and therefore tanning bed use was top of mind,” he said.

While he believes this study may not be most efficient way of determining demographics of at-risk individuals using tanning beds, Dr. Friedman said the results “should serve as the impetus to develop public health campaigns around this information, following which research can be conducted to evaluate if the intervention had an impact.”

Ms. Brown and Dr. Friedman reported no relevant financial disclosures.

Evaluation of a large insurance claims database has provided some insight into how ICD-10 indoor tanning codes are being used in practice, according to a study presented at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

“Since indoor tanning ICD-10 codes were only recently universally implemented in 2015, and providers may still be using other codes that cover similar services, we think our data likely underestimate the number of encounters and sequelae associated with indoor tanning,” Alexandria M. Brown, BSA, of Baylor College of Medicine, Houston, said in her presentation. “We think increased usage of these indoor tanning exposure codes in coming years will strengthen this body of indoor tanning literature and data.”

Using insurance claims data on about 43 million patients from Truven Health MarketScan, Ms. Brown and colleagues analyzed patient encounters with ICD-10 indoor tanning codes W89.1, W89.1XXA, W89.1XXD, and W89.1XXS between 2016 and 2018 for about 43 million patients. Overall, there were 4,550 patient encounters where these codes had been recorded, with most (99%) occurring in an outpatient setting. The majority of providers at these encounters were dermatologists (72%). Patients were mostly women (85%); and most were ages 25-34 years (19.4%), 35-44 years (20.6%), 45-54 years (22.7%), and 55-64 years (19%). Almost 5% were 65 and over, 11.7% were ages 18-24, and 1.6% were under age 18.

The use of indoor tanning codes were most common in the Midwest (55 per 100,000 encounters with dermatologists), compared with 16 per 100,000 in the Northeast, 21 per 100,000 in the West, and 28 per 100,000 in the South. CPT codes for “destruction of a premalignant lesion” and “biopsy” were the most frequently used codes entered at visits where indoor tanning codes were also entered, and were present in 15.1% of encounters and 18.4% of encounters, respectively.

“This suggests that many of these encounters may have been for skin cancer surveillance and that indoor tanning exposure may have been coded as part of a patient’s skin cancer risk profile,” Ms. Brown noted.

The study shows how these codes are being used and could help determine health care use patterns for these patients as well as their comorbidities, behaviors, and risk factors, according to the authors, who believe this is the first study to look at the use of ICD-10 indoor tanning codes.

“Any effort to reduce indoor tanning requires knowledge of the population at risk. It has been shown that the ability to recognize and provide counseling to at-risk patients can improve sun protective behaviors and reduce indoor tanning,” Ms. Brown said. Claims databases can be a “valuable tool to better understand patients who have been exposed to indoor tanning and their associated risk factors, comorbidities, behaviors, and health care utilization.”

In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said the study was interesting and “provides some guidance with respect to who, when, and where in the U.S. to target educational initiatives on the harms of tanning beds.”

Dr. Friedman, who was not involved with the research, agreed with the authors’ assertion that their study was underestimating the use of indoor tanning beds. “Using a large database provides the means to better generalize one’s dataset; however in this case, it relies on proper coding by the practitioner,” or even using the code for tanning bed use at all.

“There also could be some inherent bias given most of the cases for which the code was used was for skin cancer surveillance, and therefore tanning bed use was top of mind,” he said.

While he believes this study may not be most efficient way of determining demographics of at-risk individuals using tanning beds, Dr. Friedman said the results “should serve as the impetus to develop public health campaigns around this information, following which research can be conducted to evaluate if the intervention had an impact.”

Ms. Brown and Dr. Friedman reported no relevant financial disclosures.

Liraglutide and insulin glargine outperformed glimepiride and sitagliptin as single add-on agents to metformin for treating patients with type 2 diabetes in a multicenter U.S. trial that randomized just over 5,000 patients.

The GRADE trial ran for roughly 5 years at 36 U.S. centers and was designed to answer the question of which is the best second-line agent for patients with type 2 diabetes already taking metformin. Results were reported at the virtual American Diabetes Association (ADA) 81st Scientific Sessions. 

The comparison included two oral medications – the sulfonylurea glimepiride and dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin – and two injectable medications – insulin glargine and glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide.

The primary endpoint was change in A1c level and overall glycemic control. Secondary endpoints include changes in weight, as well as cardiovascular, renal, gastrointestinal, and other complications.

For the primary endpoint – keeping A1c levels below 7% – liraglutide and the basal insulin glargine both did this best and were almost equivalent.

During the average 5-year follow-up, the rates of patients progressing to a confirmed A1c of 7% or higher were 67% among patients randomized to insulin glargine, 68% maintained on liraglutide, 72% taking the sulfonylurea glimepiride, and 77% taking sitagliptin, reported John M. Lachin, ScD, a biostatistician at George Washington University, Washington.
 

Too soon for take-aways, or are the data already obsolete?

“The ultimate goal of GRADE is to help clinicians select the therapies that will work best for individual patients, as diabetes care is not a one-size-fits all approach,” noted David M. Nathan, MD, chair of the study and director of the Diabetes Center at Massachusetts General Hospital, in an ADA press release.

Dr. Nathan, as well as several other members of the GRADE trial steering committee who presented results, repeatedly cautioned that the findings were preliminary because they represent 90% of outcomes, with the remaining 10% still to be adjudicated.

“We undertook this study to fill a gap in the guidelines,” said investigator Deborah J. Wexler, MD, clinical director of the Diabetes Center at Massachusetts General Hospital in Boston. “I would like to have all the results in ... before I comment on how the guidelines should change.”

“The metabolic data are solid, but the cardiovascular disease data are preliminary,” warned Dr. Nathan.

But that didn’t stop some from drawing their own conclusions, with Julio Rosenstock, MD, who comoderated the session but was not involved with the study, giving his own opinion.

“A pleasant surprise was the performance of basal insulin,” he said, calling the findings “a vindication” for basal insulin as a treatment for the types of patients with type 2 diabetes that enrolled in the study.

Steven E. Kahn, MB, ChB, another GRADE co-investigator agreed. “Based on the results, guidelines should say that you add insulin early on,” he observed.

A generic basal insulin and a generic sulfonylurea are both reasonable options, after metformin, for patients with limited resources, added Dr. Kahn, an endocrinologist and professor at the University of Washington, Seattle.

Dr. Rosenstock, director of the Dallas Diabetes Research Center, also saw the results as an indictment of agents in the DDP-4 inhibitor class, such as sitagliptin.

The DPP-4 inhibitors generate $9 billion a year, he said, wondering whether it “is justifiable to put them on the same level as other agents?”

Meanwhile the assigned discussant, David R. Matthews, DPhil, a professor of diabetes medicine at the University of Oxford, England – while congratulating the investigators on certain aspects of the study – said it ultimately fell short because it didn’t include an arm with an SGLT2 inhibitor.

“We should kick the authors for missing out on SGLT2 inhibitors,” Dr. Matthews said. “The omission means that the GRADE data are already obsolescent.”

In reply, Dr. Nathan admitted “we feel bad we did not include” an SGLT2 inhibitor, but he vigorously defended the dilemma faced by the trial’s organizers.

Oral SGLT2 inhibitors were not “well-established drugs” for type 2 diabetes when enrollment launched in 2013, and the researchers were wary of including what could turn out to be a problematic agent soon after controversy over the safety of agents in the thiazolidinedione drug class (such as rosiglitazone), he explained.

They also realized that adding a fifth drug to the study would necessitate doubling enrollment size, which would have undercut the funding plans already in place.

Dr. Matthews also derided GRADE as being underpowered to adequately address the impact of the tested agents on major adverse cardiovascular events (MACE) and hospitalizations for heart failure and too U.S.-centric to be generalizable elsewhere.
 

A study with lots of data

The roughly 5,000 patients enrolled in GRADE were an average age of 57 years old, 64% were men, 66% were White, and 20% were Black. They had had type 2 diabetes, on average, for 4.2 years. Mean body mass index at entry was about 34 kg/m², average A1c was 7.5%, and average estimated glomerular filtration rate was 95 mL/min/1.73m². The trial included a 6-12 week run-in period during which background metformin treatment was optimized and led to average A1c levels less than 7%.

Patients were then randomized to one of the four agents as add-on treatment.

Both liraglutide and insulin glargine performed well on many of the numerous metrics in the data-rich trial, largely funded by two branches of the National Institutes of Health, with commercial involvement limited to free supplies of the study drugs.

The secondary metabolic outcome, of disease progressing to a confirmed A1c of 7.5%, was reached by 39% of patients taking insulin glargine, significantly lower than the rate of 46% among patients taking liraglutide, and that rate, in turn, was significantly below the 50% rate among patients taking glimepiride and the 55% rate of those taking sitagliptin.

Mean doses of the second-line agents after 4 years of treatment were 38.3 units/day for glargine, 3.5 mg/day for glimepiride, 1.3 mg/day for subcutaneous liraglutide, and 82.9 mg/day for sitagliptin. 

A trio of cardiovascular outcomes showed one significant benefit of liraglutide over the other three drugs for the endpoint of any cardiovascular event, which included not only major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, or stroke), but also several other event types, including heart failure requiring hospitalization, unstable angina requiring hospitalization, revascularization or any arterial repairs, stent thrombosis, or transient ischemic attack.

For the endpoint of any cardiovascular event, the rate was 5.8% for patients taking liraglutide, significantly less than the rate of 7.6% of those taking insulin glargine, 8.0% for glimepiride, and 8.6% for sitagliptin, reported John B. Buse, MD, PhD, professor, chief of endocrinology, and director of the Diabetes Center at the University of North Carolina at Chapel Hill.

For each of the other two main cardiovascular endpoints – MACE and hospitalization for heart failure – liraglutide had a numeric advantage over the other three drugs but failed to reach significance. 

Patients taking liraglutide also had a smaller but not significantly different point estimate for all-cause death, at 2.1%, compared with 3.1%-3.4% in the other three groups.

And, Dr. Nathan emphasized, the cardiovascular disease data are still considered preliminary.

Liraglutide scored a pair of additional outcome victories. Its use resulted in a significantly lower rate of patients who progressed during follow-up to either needing antihypertensive medications or having their blood pressure rise above 140/90 mm Hg compared with the other three drugs. (At baseline, average blood pressure for all patients was 128/77 mm Hg.)

And after 4 years, patients taking liraglutide lost an average of about 4 kg (8.8 lb) from their baseline weight (which averaged about 100 kg [220 lb]), roughly the same as patients taking sitagliptin but significantly better than with glimepiride or insulin glargine. Patients taking glargine gained a small amount of weight on average during their first couple of years of treatment, roughly 1 kg, but returned to around their baseline weight by the end of 4 years.
 

Four drugs performed equally well for some outcomes

Finally, the four drugs had similar results for some outcomes. This included their effects on renal function, distal sensory polyneuropathy, and low-density lipoprotein (LDL) cholesterol.

The four agents also had roughly similar safety profiles, with rates of serious adverse events all falling within the tight range of 33%-37%.

But the rate of severe hypoglycemic episodes that required assistance to treat showed significant separation, ranging from 2.3% for glimepiride, 1.4% for glargine, 0.9% for liraglutide, and 0.7% for sitagliptin. Gastrointestinal symptoms occurred in about 50% of patients in three of the treatment groups but were significantly higher in those taking liraglutide, affecting 60%.

GRADE received no commercial funding. Dr. Wexler has reported serving on data monitoring committees for Novo Nordisk. Dr. Buse has reported being a consultant for and holding stock in numerous companies. Dr. Rosenstock has reported being an advisor or consultant to Applied Therapeutics, Boehringer Ingelheim, Hanmi Pharmaceutical, Intarcia Therapeutics, Lilly, Novo Nordisk, Oramed, and Sanofi and has received research support from numerous companies. Dr. Kahn has reported being an advisor to or speaker on behalf of Bayer, Boehringer Ingelheim, Casma Therapeutics, Intarcia Therapeutics, Lilly, Merck, Novo Nordisk, Pfizer, and Third Rock Ventures. Dr. Matthews has reported receiving lecture and advisor fees from Merck, Novartis, Novo Nordisk, Sanofi Aventis, and Servier. Dr. Lachin and Dr. Nathan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Liraglutide and insulin glargine outperformed glimepiride and sitagliptin as single add-on agents to metformin for treating patients with type 2 diabetes in a multicenter U.S. trial that randomized just over 5,000 patients.

The GRADE trial ran for roughly 5 years at 36 U.S. centers and was designed to answer the question of which is the best second-line agent for patients with type 2 diabetes already taking metformin. Results were reported at the virtual American Diabetes Association (ADA) 81st Scientific Sessions. 

The comparison included two oral medications – the sulfonylurea glimepiride and dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin – and two injectable medications – insulin glargine and glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide.

The primary endpoint was change in A1c level and overall glycemic control. Secondary endpoints include changes in weight, as well as cardiovascular, renal, gastrointestinal, and other complications.

For the primary endpoint – keeping A1c levels below 7% – liraglutide and the basal insulin glargine both did this best and were almost equivalent.

During the average 5-year follow-up, the rates of patients progressing to a confirmed A1c of 7% or higher were 67% among patients randomized to insulin glargine, 68% maintained on liraglutide, 72% taking the sulfonylurea glimepiride, and 77% taking sitagliptin, reported John M. Lachin, ScD, a biostatistician at George Washington University, Washington.
 

Too soon for take-aways, or are the data already obsolete?

“The ultimate goal of GRADE is to help clinicians select the therapies that will work best for individual patients, as diabetes care is not a one-size-fits all approach,” noted David M. Nathan, MD, chair of the study and director of the Diabetes Center at Massachusetts General Hospital, in an ADA press release.

Dr. Nathan, as well as several other members of the GRADE trial steering committee who presented results, repeatedly cautioned that the findings were preliminary because they represent 90% of outcomes, with the remaining 10% still to be adjudicated.

“We undertook this study to fill a gap in the guidelines,” said investigator Deborah J. Wexler, MD, clinical director of the Diabetes Center at Massachusetts General Hospital in Boston. “I would like to have all the results in ... before I comment on how the guidelines should change.”

“The metabolic data are solid, but the cardiovascular disease data are preliminary,” warned Dr. Nathan.

But that didn’t stop some from drawing their own conclusions, with Julio Rosenstock, MD, who comoderated the session but was not involved with the study, giving his own opinion.

“A pleasant surprise was the performance of basal insulin,” he said, calling the findings “a vindication” for basal insulin as a treatment for the types of patients with type 2 diabetes that enrolled in the study.

Steven E. Kahn, MB, ChB, another GRADE co-investigator agreed. “Based on the results, guidelines should say that you add insulin early on,” he observed.

A generic basal insulin and a generic sulfonylurea are both reasonable options, after metformin, for patients with limited resources, added Dr. Kahn, an endocrinologist and professor at the University of Washington, Seattle.

Dr. Rosenstock, director of the Dallas Diabetes Research Center, also saw the results as an indictment of agents in the DDP-4 inhibitor class, such as sitagliptin.

The DPP-4 inhibitors generate $9 billion a year, he said, wondering whether it “is justifiable to put them on the same level as other agents?”

Meanwhile the assigned discussant, David R. Matthews, DPhil, a professor of diabetes medicine at the University of Oxford, England – while congratulating the investigators on certain aspects of the study – said it ultimately fell short because it didn’t include an arm with an SGLT2 inhibitor.

“We should kick the authors for missing out on SGLT2 inhibitors,” Dr. Matthews said. “The omission means that the GRADE data are already obsolescent.”

In reply, Dr. Nathan admitted “we feel bad we did not include” an SGLT2 inhibitor, but he vigorously defended the dilemma faced by the trial’s organizers.

Oral SGLT2 inhibitors were not “well-established drugs” for type 2 diabetes when enrollment launched in 2013, and the researchers were wary of including what could turn out to be a problematic agent soon after controversy over the safety of agents in the thiazolidinedione drug class (such as rosiglitazone), he explained.

They also realized that adding a fifth drug to the study would necessitate doubling enrollment size, which would have undercut the funding plans already in place.

Dr. Matthews also derided GRADE as being underpowered to adequately address the impact of the tested agents on major adverse cardiovascular events (MACE) and hospitalizations for heart failure and too U.S.-centric to be generalizable elsewhere.
 

A study with lots of data

The roughly 5,000 patients enrolled in GRADE were an average age of 57 years old, 64% were men, 66% were White, and 20% were Black. They had had type 2 diabetes, on average, for 4.2 years. Mean body mass index at entry was about 34 kg/m², average A1c was 7.5%, and average estimated glomerular filtration rate was 95 mL/min/1.73m². The trial included a 6-12 week run-in period during which background metformin treatment was optimized and led to average A1c levels less than 7%.

Patients were then randomized to one of the four agents as add-on treatment.

Both liraglutide and insulin glargine performed well on many of the numerous metrics in the data-rich trial, largely funded by two branches of the National Institutes of Health, with commercial involvement limited to free supplies of the study drugs.

The secondary metabolic outcome, of disease progressing to a confirmed A1c of 7.5%, was reached by 39% of patients taking insulin glargine, significantly lower than the rate of 46% among patients taking liraglutide, and that rate, in turn, was significantly below the 50% rate among patients taking glimepiride and the 55% rate of those taking sitagliptin.

Mean doses of the second-line agents after 4 years of treatment were 38.3 units/day for glargine, 3.5 mg/day for glimepiride, 1.3 mg/day for subcutaneous liraglutide, and 82.9 mg/day for sitagliptin. 

A trio of cardiovascular outcomes showed one significant benefit of liraglutide over the other three drugs for the endpoint of any cardiovascular event, which included not only major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, or stroke), but also several other event types, including heart failure requiring hospitalization, unstable angina requiring hospitalization, revascularization or any arterial repairs, stent thrombosis, or transient ischemic attack.

For the endpoint of any cardiovascular event, the rate was 5.8% for patients taking liraglutide, significantly less than the rate of 7.6% of those taking insulin glargine, 8.0% for glimepiride, and 8.6% for sitagliptin, reported John B. Buse, MD, PhD, professor, chief of endocrinology, and director of the Diabetes Center at the University of North Carolina at Chapel Hill.

For each of the other two main cardiovascular endpoints – MACE and hospitalization for heart failure – liraglutide had a numeric advantage over the other three drugs but failed to reach significance. 

Patients taking liraglutide also had a smaller but not significantly different point estimate for all-cause death, at 2.1%, compared with 3.1%-3.4% in the other three groups.

And, Dr. Nathan emphasized, the cardiovascular disease data are still considered preliminary.

Liraglutide scored a pair of additional outcome victories. Its use resulted in a significantly lower rate of patients who progressed during follow-up to either needing antihypertensive medications or having their blood pressure rise above 140/90 mm Hg compared with the other three drugs. (At baseline, average blood pressure for all patients was 128/77 mm Hg.)

And after 4 years, patients taking liraglutide lost an average of about 4 kg (8.8 lb) from their baseline weight (which averaged about 100 kg [220 lb]), roughly the same as patients taking sitagliptin but significantly better than with glimepiride or insulin glargine. Patients taking glargine gained a small amount of weight on average during their first couple of years of treatment, roughly 1 kg, but returned to around their baseline weight by the end of 4 years.
 

Four drugs performed equally well for some outcomes

Finally, the four drugs had similar results for some outcomes. This included their effects on renal function, distal sensory polyneuropathy, and low-density lipoprotein (LDL) cholesterol.

The four agents also had roughly similar safety profiles, with rates of serious adverse events all falling within the tight range of 33%-37%.

But the rate of severe hypoglycemic episodes that required assistance to treat showed significant separation, ranging from 2.3% for glimepiride, 1.4% for glargine, 0.9% for liraglutide, and 0.7% for sitagliptin. Gastrointestinal symptoms occurred in about 50% of patients in three of the treatment groups but were significantly higher in those taking liraglutide, affecting 60%.

GRADE received no commercial funding. Dr. Wexler has reported serving on data monitoring committees for Novo Nordisk. Dr. Buse has reported being a consultant for and holding stock in numerous companies. Dr. Rosenstock has reported being an advisor or consultant to Applied Therapeutics, Boehringer Ingelheim, Hanmi Pharmaceutical, Intarcia Therapeutics, Lilly, Novo Nordisk, Oramed, and Sanofi and has received research support from numerous companies. Dr. Kahn has reported being an advisor to or speaker on behalf of Bayer, Boehringer Ingelheim, Casma Therapeutics, Intarcia Therapeutics, Lilly, Merck, Novo Nordisk, Pfizer, and Third Rock Ventures. Dr. Matthews has reported receiving lecture and advisor fees from Merck, Novartis, Novo Nordisk, Sanofi Aventis, and Servier. Dr. Lachin and Dr. Nathan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Liraglutide and insulin glargine outperformed glimepiride and sitagliptin as single add-on agents to metformin for treating patients with type 2 diabetes in a multicenter U.S. trial that randomized just over 5,000 patients.

The GRADE trial ran for roughly 5 years at 36 U.S. centers and was designed to answer the question of which is the best second-line agent for patients with type 2 diabetes already taking metformin. Results were reported at the virtual American Diabetes Association (ADA) 81st Scientific Sessions. 

The comparison included two oral medications – the sulfonylurea glimepiride and dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin – and two injectable medications – insulin glargine and glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide.

The primary endpoint was change in A1c level and overall glycemic control. Secondary endpoints include changes in weight, as well as cardiovascular, renal, gastrointestinal, and other complications.

For the primary endpoint – keeping A1c levels below 7% – liraglutide and the basal insulin glargine both did this best and were almost equivalent.

During the average 5-year follow-up, the rates of patients progressing to a confirmed A1c of 7% or higher were 67% among patients randomized to insulin glargine, 68% maintained on liraglutide, 72% taking the sulfonylurea glimepiride, and 77% taking sitagliptin, reported John M. Lachin, ScD, a biostatistician at George Washington University, Washington.
 

Too soon for take-aways, or are the data already obsolete?

“The ultimate goal of GRADE is to help clinicians select the therapies that will work best for individual patients, as diabetes care is not a one-size-fits all approach,” noted David M. Nathan, MD, chair of the study and director of the Diabetes Center at Massachusetts General Hospital, in an ADA press release.

Dr. Nathan, as well as several other members of the GRADE trial steering committee who presented results, repeatedly cautioned that the findings were preliminary because they represent 90% of outcomes, with the remaining 10% still to be adjudicated.

“We undertook this study to fill a gap in the guidelines,” said investigator Deborah J. Wexler, MD, clinical director of the Diabetes Center at Massachusetts General Hospital in Boston. “I would like to have all the results in ... before I comment on how the guidelines should change.”

“The metabolic data are solid, but the cardiovascular disease data are preliminary,” warned Dr. Nathan.

But that didn’t stop some from drawing their own conclusions, with Julio Rosenstock, MD, who comoderated the session but was not involved with the study, giving his own opinion.

“A pleasant surprise was the performance of basal insulin,” he said, calling the findings “a vindication” for basal insulin as a treatment for the types of patients with type 2 diabetes that enrolled in the study.

Steven E. Kahn, MB, ChB, another GRADE co-investigator agreed. “Based on the results, guidelines should say that you add insulin early on,” he observed.

A generic basal insulin and a generic sulfonylurea are both reasonable options, after metformin, for patients with limited resources, added Dr. Kahn, an endocrinologist and professor at the University of Washington, Seattle.

Dr. Rosenstock, director of the Dallas Diabetes Research Center, also saw the results as an indictment of agents in the DDP-4 inhibitor class, such as sitagliptin.

The DPP-4 inhibitors generate $9 billion a year, he said, wondering whether it “is justifiable to put them on the same level as other agents?”

Meanwhile the assigned discussant, David R. Matthews, DPhil, a professor of diabetes medicine at the University of Oxford, England – while congratulating the investigators on certain aspects of the study – said it ultimately fell short because it didn’t include an arm with an SGLT2 inhibitor.

“We should kick the authors for missing out on SGLT2 inhibitors,” Dr. Matthews said. “The omission means that the GRADE data are already obsolescent.”

In reply, Dr. Nathan admitted “we feel bad we did not include” an SGLT2 inhibitor, but he vigorously defended the dilemma faced by the trial’s organizers.

Oral SGLT2 inhibitors were not “well-established drugs” for type 2 diabetes when enrollment launched in 2013, and the researchers were wary of including what could turn out to be a problematic agent soon after controversy over the safety of agents in the thiazolidinedione drug class (such as rosiglitazone), he explained.

They also realized that adding a fifth drug to the study would necessitate doubling enrollment size, which would have undercut the funding plans already in place.

Dr. Matthews also derided GRADE as being underpowered to adequately address the impact of the tested agents on major adverse cardiovascular events (MACE) and hospitalizations for heart failure and too U.S.-centric to be generalizable elsewhere.
 

A study with lots of data

The roughly 5,000 patients enrolled in GRADE were an average age of 57 years old, 64% were men, 66% were White, and 20% were Black. They had had type 2 diabetes, on average, for 4.2 years. Mean body mass index at entry was about 34 kg/m², average A1c was 7.5%, and average estimated glomerular filtration rate was 95 mL/min/1.73m². The trial included a 6-12 week run-in period during which background metformin treatment was optimized and led to average A1c levels less than 7%.

Patients were then randomized to one of the four agents as add-on treatment.

Both liraglutide and insulin glargine performed well on many of the numerous metrics in the data-rich trial, largely funded by two branches of the National Institutes of Health, with commercial involvement limited to free supplies of the study drugs.

The secondary metabolic outcome, of disease progressing to a confirmed A1c of 7.5%, was reached by 39% of patients taking insulin glargine, significantly lower than the rate of 46% among patients taking liraglutide, and that rate, in turn, was significantly below the 50% rate among patients taking glimepiride and the 55% rate of those taking sitagliptin.

Mean doses of the second-line agents after 4 years of treatment were 38.3 units/day for glargine, 3.5 mg/day for glimepiride, 1.3 mg/day for subcutaneous liraglutide, and 82.9 mg/day for sitagliptin. 

A trio of cardiovascular outcomes showed one significant benefit of liraglutide over the other three drugs for the endpoint of any cardiovascular event, which included not only major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, or stroke), but also several other event types, including heart failure requiring hospitalization, unstable angina requiring hospitalization, revascularization or any arterial repairs, stent thrombosis, or transient ischemic attack.

For the endpoint of any cardiovascular event, the rate was 5.8% for patients taking liraglutide, significantly less than the rate of 7.6% of those taking insulin glargine, 8.0% for glimepiride, and 8.6% for sitagliptin, reported John B. Buse, MD, PhD, professor, chief of endocrinology, and director of the Diabetes Center at the University of North Carolina at Chapel Hill.

For each of the other two main cardiovascular endpoints – MACE and hospitalization for heart failure – liraglutide had a numeric advantage over the other three drugs but failed to reach significance. 

Patients taking liraglutide also had a smaller but not significantly different point estimate for all-cause death, at 2.1%, compared with 3.1%-3.4% in the other three groups.

And, Dr. Nathan emphasized, the cardiovascular disease data are still considered preliminary.

Liraglutide scored a pair of additional outcome victories. Its use resulted in a significantly lower rate of patients who progressed during follow-up to either needing antihypertensive medications or having their blood pressure rise above 140/90 mm Hg compared with the other three drugs. (At baseline, average blood pressure for all patients was 128/77 mm Hg.)

And after 4 years, patients taking liraglutide lost an average of about 4 kg (8.8 lb) from their baseline weight (which averaged about 100 kg [220 lb]), roughly the same as patients taking sitagliptin but significantly better than with glimepiride or insulin glargine. Patients taking glargine gained a small amount of weight on average during their first couple of years of treatment, roughly 1 kg, but returned to around their baseline weight by the end of 4 years.
 

Four drugs performed equally well for some outcomes

Finally, the four drugs had similar results for some outcomes. This included their effects on renal function, distal sensory polyneuropathy, and low-density lipoprotein (LDL) cholesterol.

The four agents also had roughly similar safety profiles, with rates of serious adverse events all falling within the tight range of 33%-37%.

But the rate of severe hypoglycemic episodes that required assistance to treat showed significant separation, ranging from 2.3% for glimepiride, 1.4% for glargine, 0.9% for liraglutide, and 0.7% for sitagliptin. Gastrointestinal symptoms occurred in about 50% of patients in three of the treatment groups but were significantly higher in those taking liraglutide, affecting 60%.

GRADE received no commercial funding. Dr. Wexler has reported serving on data monitoring committees for Novo Nordisk. Dr. Buse has reported being a consultant for and holding stock in numerous companies. Dr. Rosenstock has reported being an advisor or consultant to Applied Therapeutics, Boehringer Ingelheim, Hanmi Pharmaceutical, Intarcia Therapeutics, Lilly, Novo Nordisk, Oramed, and Sanofi and has received research support from numerous companies. Dr. Kahn has reported being an advisor to or speaker on behalf of Bayer, Boehringer Ingelheim, Casma Therapeutics, Intarcia Therapeutics, Lilly, Merck, Novo Nordisk, Pfizer, and Third Rock Ventures. Dr. Matthews has reported receiving lecture and advisor fees from Merck, Novartis, Novo Nordisk, Sanofi Aventis, and Servier. Dr. Lachin and Dr. Nathan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women who have even mild sleep apnea should be treated for their sleep-disordered breathing given what is known about associated risks for hypertensive disorders of pregnancy and gestational diabetes, Carolyn M. D’Ambrosio, MS, MD, FCCP, said at the virtual annual meeting of the Associated Professional Sleep Societies.

“This is the current standard of care,” Dr. D’Ambrosio said. “Although guidelines on this issue are not hard and fast, I’d say that knowing what we know about the risk of adverse [maternal] outcomes, we should all try to treat these problems as soon as they’re identified” and then repeat polysomnography or home sleep testing 3-6 months post partum to “be sure the sleep-disordered breathing has resolved.”

Estimates of obstructive sleep apnea (OSA) prevalence range from approximately 9% in the first trimester to 20% in the third trimester. Yet recognizing the significance of OSA in pregnant women and identifying women for testing remains a major challenge. “Most women won’t [report sleep problems] because it’s pretty much common folklore that you don’t sleep well when you’re pregnant,” said Dr. D’Ambrosio, associate professor of medicine at Harvard Medical School, Boston, and current past-chair of the Women’s Lung Health Network for CHEST.

Many obstetricians and obstetrics providers, meanwhile, do not adequately screen. Typical screening tools like the Epworth Sleepiness Scale have low sensitivity and specificity during pregnancy, which means that inquiries about sleepiness, snoring, and disruptions in sleep are important, as is attention to potential risks for OSA posed by obesity, chronic hypertension, and neck circumference.

Only about a quarter of women in the United States snore during pregnancy, she noted. Snoring prevalence does increase as pregnancy progresses, reaching up to almost 50% in during the third trimester in some studies.

A four-variable screening tool reported almost 10 years ago for pregnant women is reliable for gauging risk, Dr. D’Ambrosio said. The model considers self-reported frequent snoring (more than three times/week), chronic hypertension, advanced maternal age, and a pregestational body mass index of at least 30 kg/m². “If these [factors] are present, the patient is at significant risk for OSA and should be strongly considered for testing,” she said.

Home sleep apnea testing (HSAT) is validated for pregnant women but “it can underestimate,” she said. “If you get a negative result and [have clinical suspicion], then don’t stop there.”

And considering that the prevalence of OSA – at all levels of severity – increases as pregnancy progresses, it’s important to continue talking about sleep with patients who have frequent snoring, for instance, but negative sleep test results early in pregnancy. “They could develop [OSA] as time goes on,” she said.
 

Associated risk factors

Independent associations between sleep-disordered breathing and adverse maternal outcomes were demonstrated in a prospective cohort study published several years ago of 3,705 women who underwent HSAT in early and mid-pregnancy. The adjusted odds ratios for preeclampsia when sleep-disordered breathing (an apnea-hypopnea index of ≥5) was present early in pregnancy and in mid-pregnancy were 1.94 and 1.95, respectively.

For hypertensive disorders of pregnancy more broadly, the ORs were 1.46 and 1.73, and for gestational diabetes, the ORs were 3.47 and 2.79.

“Faced with the question about why it’s important to diagnosis and treat OSA [during pregnancy] since the pregnancy will be over in a few months, I go to this study,” Dr. D’Ambrosio said. “Waiting until the end of pregnancy is not safe. There are increased risks of very serious conditions if sleep apnea is there and it’s not treated.”

Another study demonstrating a link between OSA and maternal outcomes looked over 1.5 million deliveries in the United States and found a significantly higher prevalence of gestational diabetes (OR, 2.08), gestational hypertension (OR, 1.77), preeclampsia (OR, 2.07), and eclampsia (OR, 2.70) in pregnant women with OSA than without, after adjusting for maternal obesity. Associations remained significant after adjusting for a more comprehensive list of covariates.

Multiple potential casual pathways are at play, Dr. D’Ambrosio said. Short sleep duration decreases leptin and increases ghrelin levels, for instance, and sleep fragmentation activates the HPA axis and increases cortisol. Intermittent hypoxemia affects sympathetic activity, and intrathoracic pressure swings cause increased oxidative stress and systemic inflammation.

The resulting endothelial dysfunction, glucose dysfunction, and dyslipidemia can drive the adverse maternal outcomes documented in these studies, she said, noting that the adverse outcomes can have long-term cardiovascular consequences.

Continuous positive airway pressure therapy is well tolerated in pregnancy, and given pregnancy’s continual weight change, auto-titrating CPAP may be the best option, she said.

There is “some limited data that treatment improves maternal outcomes, and we’re still working on trying to get better data and more solid recommendations,” Dr. D’Ambrosio said. There currently are no guidelines covering the diagnosis and management of OSA during pregnancy.

“We’ve come a long way ... but we still have more to do,” she said. “We have a long way to go to getting [OSA in pregnant women] well recognized, with screening techniques and diagnosis.”

Asked after the meeting about Dr. D’Ambrosio’s messages, Anita Rajagopal, MD, said that OSA screening during pregnancy needs to be improved through more collaboration “with our ob.gyn. and primary care colleagues.”

Too often, she said, “the signs and symptoms of OSA in pregnancy are written off as ‘just harmless snoring’ while in fact the patient has treatable sleep disordered breathing with potential adverse effects.” Dr. Rajagopal is department medical director for sleep medicine at Community Physician Network and medical director of the Community Health Network Sleep-Wake Disorders Center, both in Indianapolis.

Dr. D’Ambrosio reported that she has no potential conflicts of interest related to the material she presented, and Dr. Rajagopal stated she has no potential conflicts of interest.

Pregnant women who have even mild sleep apnea should be treated for their sleep-disordered breathing given what is known about associated risks for hypertensive disorders of pregnancy and gestational diabetes, Carolyn M. D’Ambrosio, MS, MD, FCCP, said at the virtual annual meeting of the Associated Professional Sleep Societies.

“This is the current standard of care,” Dr. D’Ambrosio said. “Although guidelines on this issue are not hard and fast, I’d say that knowing what we know about the risk of adverse [maternal] outcomes, we should all try to treat these problems as soon as they’re identified” and then repeat polysomnography or home sleep testing 3-6 months post partum to “be sure the sleep-disordered breathing has resolved.”

Estimates of obstructive sleep apnea (OSA) prevalence range from approximately 9% in the first trimester to 20% in the third trimester. Yet recognizing the significance of OSA in pregnant women and identifying women for testing remains a major challenge. “Most women won’t [report sleep problems] because it’s pretty much common folklore that you don’t sleep well when you’re pregnant,” said Dr. D’Ambrosio, associate professor of medicine at Harvard Medical School, Boston, and current past-chair of the Women’s Lung Health Network for CHEST.

Many obstetricians and obstetrics providers, meanwhile, do not adequately screen. Typical screening tools like the Epworth Sleepiness Scale have low sensitivity and specificity during pregnancy, which means that inquiries about sleepiness, snoring, and disruptions in sleep are important, as is attention to potential risks for OSA posed by obesity, chronic hypertension, and neck circumference.

Only about a quarter of women in the United States snore during pregnancy, she noted. Snoring prevalence does increase as pregnancy progresses, reaching up to almost 50% in during the third trimester in some studies.

A four-variable screening tool reported almost 10 years ago for pregnant women is reliable for gauging risk, Dr. D’Ambrosio said. The model considers self-reported frequent snoring (more than three times/week), chronic hypertension, advanced maternal age, and a pregestational body mass index of at least 30 kg/m². “If these [factors] are present, the patient is at significant risk for OSA and should be strongly considered for testing,” she said.

Home sleep apnea testing (HSAT) is validated for pregnant women but “it can underestimate,” she said. “If you get a negative result and [have clinical suspicion], then don’t stop there.”

And considering that the prevalence of OSA – at all levels of severity – increases as pregnancy progresses, it’s important to continue talking about sleep with patients who have frequent snoring, for instance, but negative sleep test results early in pregnancy. “They could develop [OSA] as time goes on,” she said.
 

Associated risk factors

Independent associations between sleep-disordered breathing and adverse maternal outcomes were demonstrated in a prospective cohort study published several years ago of 3,705 women who underwent HSAT in early and mid-pregnancy. The adjusted odds ratios for preeclampsia when sleep-disordered breathing (an apnea-hypopnea index of ≥5) was present early in pregnancy and in mid-pregnancy were 1.94 and 1.95, respectively.

For hypertensive disorders of pregnancy more broadly, the ORs were 1.46 and 1.73, and for gestational diabetes, the ORs were 3.47 and 2.79.

“Faced with the question about why it’s important to diagnosis and treat OSA [during pregnancy] since the pregnancy will be over in a few months, I go to this study,” Dr. D’Ambrosio said. “Waiting until the end of pregnancy is not safe. There are increased risks of very serious conditions if sleep apnea is there and it’s not treated.”

Another study demonstrating a link between OSA and maternal outcomes looked over 1.5 million deliveries in the United States and found a significantly higher prevalence of gestational diabetes (OR, 2.08), gestational hypertension (OR, 1.77), preeclampsia (OR, 2.07), and eclampsia (OR, 2.70) in pregnant women with OSA than without, after adjusting for maternal obesity. Associations remained significant after adjusting for a more comprehensive list of covariates.

Multiple potential casual pathways are at play, Dr. D’Ambrosio said. Short sleep duration decreases leptin and increases ghrelin levels, for instance, and sleep fragmentation activates the HPA axis and increases cortisol. Intermittent hypoxemia affects sympathetic activity, and intrathoracic pressure swings cause increased oxidative stress and systemic inflammation.

The resulting endothelial dysfunction, glucose dysfunction, and dyslipidemia can drive the adverse maternal outcomes documented in these studies, she said, noting that the adverse outcomes can have long-term cardiovascular consequences.

Continuous positive airway pressure therapy is well tolerated in pregnancy, and given pregnancy’s continual weight change, auto-titrating CPAP may be the best option, she said.

There is “some limited data that treatment improves maternal outcomes, and we’re still working on trying to get better data and more solid recommendations,” Dr. D’Ambrosio said. There currently are no guidelines covering the diagnosis and management of OSA during pregnancy.

“We’ve come a long way ... but we still have more to do,” she said. “We have a long way to go to getting [OSA in pregnant women] well recognized, with screening techniques and diagnosis.”

Asked after the meeting about Dr. D’Ambrosio’s messages, Anita Rajagopal, MD, said that OSA screening during pregnancy needs to be improved through more collaboration “with our ob.gyn. and primary care colleagues.”

Too often, she said, “the signs and symptoms of OSA in pregnancy are written off as ‘just harmless snoring’ while in fact the patient has treatable sleep disordered breathing with potential adverse effects.” Dr. Rajagopal is department medical director for sleep medicine at Community Physician Network and medical director of the Community Health Network Sleep-Wake Disorders Center, both in Indianapolis.

Dr. D’Ambrosio reported that she has no potential conflicts of interest related to the material she presented, and Dr. Rajagopal stated she has no potential conflicts of interest.

Pregnant women who have even mild sleep apnea should be treated for their sleep-disordered breathing given what is known about associated risks for hypertensive disorders of pregnancy and gestational diabetes, Carolyn M. D’Ambrosio, MS, MD, FCCP, said at the virtual annual meeting of the Associated Professional Sleep Societies.

“This is the current standard of care,” Dr. D’Ambrosio said. “Although guidelines on this issue are not hard and fast, I’d say that knowing what we know about the risk of adverse [maternal] outcomes, we should all try to treat these problems as soon as they’re identified” and then repeat polysomnography or home sleep testing 3-6 months post partum to “be sure the sleep-disordered breathing has resolved.”

Estimates of obstructive sleep apnea (OSA) prevalence range from approximately 9% in the first trimester to 20% in the third trimester. Yet recognizing the significance of OSA in pregnant women and identifying women for testing remains a major challenge. “Most women won’t [report sleep problems] because it’s pretty much common folklore that you don’t sleep well when you’re pregnant,” said Dr. D’Ambrosio, associate professor of medicine at Harvard Medical School, Boston, and current past-chair of the Women’s Lung Health Network for CHEST.

Many obstetricians and obstetrics providers, meanwhile, do not adequately screen. Typical screening tools like the Epworth Sleepiness Scale have low sensitivity and specificity during pregnancy, which means that inquiries about sleepiness, snoring, and disruptions in sleep are important, as is attention to potential risks for OSA posed by obesity, chronic hypertension, and neck circumference.

Only about a quarter of women in the United States snore during pregnancy, she noted. Snoring prevalence does increase as pregnancy progresses, reaching up to almost 50% in during the third trimester in some studies.

A four-variable screening tool reported almost 10 years ago for pregnant women is reliable for gauging risk, Dr. D’Ambrosio said. The model considers self-reported frequent snoring (more than three times/week), chronic hypertension, advanced maternal age, and a pregestational body mass index of at least 30 kg/m². “If these [factors] are present, the patient is at significant risk for OSA and should be strongly considered for testing,” she said.

Home sleep apnea testing (HSAT) is validated for pregnant women but “it can underestimate,” she said. “If you get a negative result and [have clinical suspicion], then don’t stop there.”

And considering that the prevalence of OSA – at all levels of severity – increases as pregnancy progresses, it’s important to continue talking about sleep with patients who have frequent snoring, for instance, but negative sleep test results early in pregnancy. “They could develop [OSA] as time goes on,” she said.
 

Associated risk factors

Independent associations between sleep-disordered breathing and adverse maternal outcomes were demonstrated in a prospective cohort study published several years ago of 3,705 women who underwent HSAT in early and mid-pregnancy. The adjusted odds ratios for preeclampsia when sleep-disordered breathing (an apnea-hypopnea index of ≥5) was present early in pregnancy and in mid-pregnancy were 1.94 and 1.95, respectively.

For hypertensive disorders of pregnancy more broadly, the ORs were 1.46 and 1.73, and for gestational diabetes, the ORs were 3.47 and 2.79.

“Faced with the question about why it’s important to diagnosis and treat OSA [during pregnancy] since the pregnancy will be over in a few months, I go to this study,” Dr. D’Ambrosio said. “Waiting until the end of pregnancy is not safe. There are increased risks of very serious conditions if sleep apnea is there and it’s not treated.”

Another study demonstrating a link between OSA and maternal outcomes looked over 1.5 million deliveries in the United States and found a significantly higher prevalence of gestational diabetes (OR, 2.08), gestational hypertension (OR, 1.77), preeclampsia (OR, 2.07), and eclampsia (OR, 2.70) in pregnant women with OSA than without, after adjusting for maternal obesity. Associations remained significant after adjusting for a more comprehensive list of covariates.

Multiple potential casual pathways are at play, Dr. D’Ambrosio said. Short sleep duration decreases leptin and increases ghrelin levels, for instance, and sleep fragmentation activates the HPA axis and increases cortisol. Intermittent hypoxemia affects sympathetic activity, and intrathoracic pressure swings cause increased oxidative stress and systemic inflammation.

The resulting endothelial dysfunction, glucose dysfunction, and dyslipidemia can drive the adverse maternal outcomes documented in these studies, she said, noting that the adverse outcomes can have long-term cardiovascular consequences.

Continuous positive airway pressure therapy is well tolerated in pregnancy, and given pregnancy’s continual weight change, auto-titrating CPAP may be the best option, she said.

There is “some limited data that treatment improves maternal outcomes, and we’re still working on trying to get better data and more solid recommendations,” Dr. D’Ambrosio said. There currently are no guidelines covering the diagnosis and management of OSA during pregnancy.

“We’ve come a long way ... but we still have more to do,” she said. “We have a long way to go to getting [OSA in pregnant women] well recognized, with screening techniques and diagnosis.”

Asked after the meeting about Dr. D’Ambrosio’s messages, Anita Rajagopal, MD, said that OSA screening during pregnancy needs to be improved through more collaboration “with our ob.gyn. and primary care colleagues.”

Too often, she said, “the signs and symptoms of OSA in pregnancy are written off as ‘just harmless snoring’ while in fact the patient has treatable sleep disordered breathing with potential adverse effects.” Dr. Rajagopal is department medical director for sleep medicine at Community Physician Network and medical director of the Community Health Network Sleep-Wake Disorders Center, both in Indianapolis.

Dr. D’Ambrosio reported that she has no potential conflicts of interest related to the material she presented, and Dr. Rajagopal stated she has no potential conflicts of interest.

Patients with multiple sclerosis (MS) may soon have another less expensive, more convenient treatment option compared with other agents in the same drug class, new research suggests.

Results from two new phase 3 trials show that the investigational drug ublituximab (TG Therapeutics), a novel glycoengineered anti-CD20 monoclonal antibody, significantly reduced the annualized relapse rate (ARR) and MRI parameters compared with teriflunomide in patients with relapsing forms of MS.

The positive results suggest “another strong and reasonably safe medication might be available to increase the repertoire of effective medicines that we can offer MS patients,” said Lawrence Steinman, MD, professor of neurology, Stanford (Calif.) University. “These are delightful data in my opinion,” he added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

‘Glycoengineered’ antibody

If approved by the U.S. Food and Drug Administration, ublituximab would become the only glycoengineered anti-CD20 monoclonal antibody for MS. Glycoengineering involves changing protein-associated carbohydrates to alter pharmacokinetic properties.

There are currently two approved anti-CD20 agents for MS, but both require 4-hour infusions. For many patients, this means “at least half their day is shot,” Dr. Steinman said. “A lot of people don’t want to or can’t miss a half day of work.” Ublituximab can be infused more rapidly, he noted.

For the study, the investigators analyzed data from the ULTIMATE I and ULTIMATE II studies, which included 1,089 mostly White patients with MS. Almost all participants had the relapsing-remitting form of the disease and were between 18 and 55 years of age (average age, 36 years). Their scores on the Expanded Disability Status Scale (EDSS) were from 0 to 5.5, and they had been neurologically stable for at least 30 days prior to screening.

Participants were required to have experienced two or more relapses within the previous 2 years or one or more relapses in the year prior and/or had one gadolinium-enhancing lesion in the year prior to screening.

The study population was mostly from the Ukraine and Russia. It is more difficult to recruit patients into MS drug studies in the United States and Western Europe because many patients in these countries are already receiving approved drugs, which deters enrollment, explained Dr. Steinman.

Investigators randomly assigned the participants to receive the investigational drug or 14 mg of oral teriflunomide, a drug that blocks the proliferation of immune cells, once daily. The ublituximab group received an initial infusion of 150 mg over 4 hours and then a 1-hour infusion of 450 mg every 6 months over the course of the 96-week study.
 

Primary outcomes met

For ULTIMATE I, the primary outcome was ARR. Results showed that this rate was 0.076 for the ublituximab group and 0.188 for the teriflunomide group, resulting in a 60% relative reduction (adjusted ARR ratio, 0.406; 95% confidence interval, 0.268-0.615; P < .0001).

In ULTIMATE II, the ARR was 0.091 for ublituximab and 0.178 for teriflunomide, for a relative reduction of 49% (ARR ratio, 0.509; 95% CI, 0.330-0.784; P = .0022).

One way of interpreting these data is that patients are likely to have only one relapse in 10 years, said Dr. Steinman. “So that was very good news.”

It is not clear why relative reductions for ARR differed between the two studies; “probably the real number is somewhere between 60% and 49%,” Dr. Steinman said.

From MRI scans, the total number of relevant lesions was reduced by 97% with ublituximab compared with teriflunomide in ULTIMATE I and by 96% in trial II.

Another “piece of really good news” from the studies is that the drug led to a significant improvement in disability, rather than “just slowing it down,” Dr. Steinman noted.

There was a 116% increased chance of confirmed disability improvement (CDI) with ublituximab versus teriflunomide in the first trial (P = .003) and a 103% increased chance of CDI in the second trial (P = .0026).

The percentage of patients who had no evidence of disease activity was 198% for the patients who received the trial drug in comparison with the control group in trial I and 277% in trial II (P < .0001 for both trials).
 

A life changer?

Dr. Steinman said the “robust” findings suggest that patients with MS “won’t have a relapse and will improve. Those are two pretty good messages for somebody with this wretched disease.”

The investigational drug was generally well tolerated. The percentage of adverse events (AEs) with the study drug was about the same as with the comparator. About 9.5% of the ublituximab group had a serious AE, compared with 6.2% of the teriflunomide group.

The ublituximab group had more infections (4.0% vs. 2.6%), which Dr. Steinman said is not surprising because the drug is a potent immune suppressant. “It’s an unfortunate consequence of this kind of strong biologic that knocks down a whole arm of the immune system. The wonder to me is that these are still rather infrequent,” he said.

If approved, “it will be interesting to see how regulatory agencies handle this in terms of risk mitigation,” said Dr. Steinman. He added that a warning label might be a consideration.

However, the safety of this drug “is certainly acceptable,” said Dr. Steinman. “In general, this drug is not that different from the other drugs in the class of anti-CD20s.”

Dr. Steinman noted that he understands why some patients prefer an oral drug and may have an “aversion to getting stuck with a needle,” but he pointed out that teriflunomide has some drawbacks. For example, it tends to thin hair.

“For people who have had relapses, people who are unable to do what they want to in life – attend school, hold down jobs, exercise – this new drug could really be life changing,” he said.

He added that he would “strongly urge” his own family and relatives, if they had MS, to take one of the anti-CD20 drugs.

Ublituximab also has a number of advantages over the other agents in the same class. Not only does it work well, have an acceptable safety profile, and require a shorter infusion time, but it could also be less costly, Dr. Steinman noted. “The company has said it intends to come in at a lower price point,” he said.

The company is now planning to prepare a biological license application for use in MS. Interestingly, the drug, in combination with umbralisib (Ukoniq), is already under review by the FDA for use in chronic lymphoctytic leukemia and small lymphocytic lymphoma.
 

Striking improvement

When session chair Marcello Moccio, MD, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy, asked Dr. Steinman to elaborate on the “very strong effect” of the drug with regard to improving disability, Dr. Steinman said the improvement was “striking.”

Being able to talk to patients about possible improvement rather than about delaying disability “is really gratifying” and provides a “much more constructive and optimistic outlook,” he said.

He noted that as physicians improve their management of patients with MS “and are paying attention to things that we haven’t over the years, like vitamin D and even mental health,” disability progression management “is getting better.”

Dr. Steinman is a consultant for TG Therapeutics.

A version of this article first appeared on Medscape.com.

Patients with multiple sclerosis (MS) may soon have another less expensive, more convenient treatment option compared with other agents in the same drug class, new research suggests.

Results from two new phase 3 trials show that the investigational drug ublituximab (TG Therapeutics), a novel glycoengineered anti-CD20 monoclonal antibody, significantly reduced the annualized relapse rate (ARR) and MRI parameters compared with teriflunomide in patients with relapsing forms of MS.

The positive results suggest “another strong and reasonably safe medication might be available to increase the repertoire of effective medicines that we can offer MS patients,” said Lawrence Steinman, MD, professor of neurology, Stanford (Calif.) University. “These are delightful data in my opinion,” he added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

‘Glycoengineered’ antibody

If approved by the U.S. Food and Drug Administration, ublituximab would become the only glycoengineered anti-CD20 monoclonal antibody for MS. Glycoengineering involves changing protein-associated carbohydrates to alter pharmacokinetic properties.

There are currently two approved anti-CD20 agents for MS, but both require 4-hour infusions. For many patients, this means “at least half their day is shot,” Dr. Steinman said. “A lot of people don’t want to or can’t miss a half day of work.” Ublituximab can be infused more rapidly, he noted.

For the study, the investigators analyzed data from the ULTIMATE I and ULTIMATE II studies, which included 1,089 mostly White patients with MS. Almost all participants had the relapsing-remitting form of the disease and were between 18 and 55 years of age (average age, 36 years). Their scores on the Expanded Disability Status Scale (EDSS) were from 0 to 5.5, and they had been neurologically stable for at least 30 days prior to screening.

Participants were required to have experienced two or more relapses within the previous 2 years or one or more relapses in the year prior and/or had one gadolinium-enhancing lesion in the year prior to screening.

The study population was mostly from the Ukraine and Russia. It is more difficult to recruit patients into MS drug studies in the United States and Western Europe because many patients in these countries are already receiving approved drugs, which deters enrollment, explained Dr. Steinman.

Investigators randomly assigned the participants to receive the investigational drug or 14 mg of oral teriflunomide, a drug that blocks the proliferation of immune cells, once daily. The ublituximab group received an initial infusion of 150 mg over 4 hours and then a 1-hour infusion of 450 mg every 6 months over the course of the 96-week study.
 

Primary outcomes met

For ULTIMATE I, the primary outcome was ARR. Results showed that this rate was 0.076 for the ublituximab group and 0.188 for the teriflunomide group, resulting in a 60% relative reduction (adjusted ARR ratio, 0.406; 95% confidence interval, 0.268-0.615; P < .0001).

In ULTIMATE II, the ARR was 0.091 for ublituximab and 0.178 for teriflunomide, for a relative reduction of 49% (ARR ratio, 0.509; 95% CI, 0.330-0.784; P = .0022).

One way of interpreting these data is that patients are likely to have only one relapse in 10 years, said Dr. Steinman. “So that was very good news.”

It is not clear why relative reductions for ARR differed between the two studies; “probably the real number is somewhere between 60% and 49%,” Dr. Steinman said.

From MRI scans, the total number of relevant lesions was reduced by 97% with ublituximab compared with teriflunomide in ULTIMATE I and by 96% in trial II.

Another “piece of really good news” from the studies is that the drug led to a significant improvement in disability, rather than “just slowing it down,” Dr. Steinman noted.

There was a 116% increased chance of confirmed disability improvement (CDI) with ublituximab versus teriflunomide in the first trial (P = .003) and a 103% increased chance of CDI in the second trial (P = .0026).

The percentage of patients who had no evidence of disease activity was 198% for the patients who received the trial drug in comparison with the control group in trial I and 277% in trial II (P < .0001 for both trials).
 

A life changer?

Dr. Steinman said the “robust” findings suggest that patients with MS “won’t have a relapse and will improve. Those are two pretty good messages for somebody with this wretched disease.”

The investigational drug was generally well tolerated. The percentage of adverse events (AEs) with the study drug was about the same as with the comparator. About 9.5% of the ublituximab group had a serious AE, compared with 6.2% of the teriflunomide group.

The ublituximab group had more infections (4.0% vs. 2.6%), which Dr. Steinman said is not surprising because the drug is a potent immune suppressant. “It’s an unfortunate consequence of this kind of strong biologic that knocks down a whole arm of the immune system. The wonder to me is that these are still rather infrequent,” he said.

If approved, “it will be interesting to see how regulatory agencies handle this in terms of risk mitigation,” said Dr. Steinman. He added that a warning label might be a consideration.

However, the safety of this drug “is certainly acceptable,” said Dr. Steinman. “In general, this drug is not that different from the other drugs in the class of anti-CD20s.”

Dr. Steinman noted that he understands why some patients prefer an oral drug and may have an “aversion to getting stuck with a needle,” but he pointed out that teriflunomide has some drawbacks. For example, it tends to thin hair.

“For people who have had relapses, people who are unable to do what they want to in life – attend school, hold down jobs, exercise – this new drug could really be life changing,” he said.

He added that he would “strongly urge” his own family and relatives, if they had MS, to take one of the anti-CD20 drugs.

Ublituximab also has a number of advantages over the other agents in the same class. Not only does it work well, have an acceptable safety profile, and require a shorter infusion time, but it could also be less costly, Dr. Steinman noted. “The company has said it intends to come in at a lower price point,” he said.

The company is now planning to prepare a biological license application for use in MS. Interestingly, the drug, in combination with umbralisib (Ukoniq), is already under review by the FDA for use in chronic lymphoctytic leukemia and small lymphocytic lymphoma.
 

Striking improvement

When session chair Marcello Moccio, MD, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy, asked Dr. Steinman to elaborate on the “very strong effect” of the drug with regard to improving disability, Dr. Steinman said the improvement was “striking.”

Being able to talk to patients about possible improvement rather than about delaying disability “is really gratifying” and provides a “much more constructive and optimistic outlook,” he said.

He noted that as physicians improve their management of patients with MS “and are paying attention to things that we haven’t over the years, like vitamin D and even mental health,” disability progression management “is getting better.”

Dr. Steinman is a consultant for TG Therapeutics.

A version of this article first appeared on Medscape.com.

Patients with multiple sclerosis (MS) may soon have another less expensive, more convenient treatment option compared with other agents in the same drug class, new research suggests.

Results from two new phase 3 trials show that the investigational drug ublituximab (TG Therapeutics), a novel glycoengineered anti-CD20 monoclonal antibody, significantly reduced the annualized relapse rate (ARR) and MRI parameters compared with teriflunomide in patients with relapsing forms of MS.

The positive results suggest “another strong and reasonably safe medication might be available to increase the repertoire of effective medicines that we can offer MS patients,” said Lawrence Steinman, MD, professor of neurology, Stanford (Calif.) University. “These are delightful data in my opinion,” he added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

‘Glycoengineered’ antibody

If approved by the U.S. Food and Drug Administration, ublituximab would become the only glycoengineered anti-CD20 monoclonal antibody for MS. Glycoengineering involves changing protein-associated carbohydrates to alter pharmacokinetic properties.

There are currently two approved anti-CD20 agents for MS, but both require 4-hour infusions. For many patients, this means “at least half their day is shot,” Dr. Steinman said. “A lot of people don’t want to or can’t miss a half day of work.” Ublituximab can be infused more rapidly, he noted.

For the study, the investigators analyzed data from the ULTIMATE I and ULTIMATE II studies, which included 1,089 mostly White patients with MS. Almost all participants had the relapsing-remitting form of the disease and were between 18 and 55 years of age (average age, 36 years). Their scores on the Expanded Disability Status Scale (EDSS) were from 0 to 5.5, and they had been neurologically stable for at least 30 days prior to screening.

Participants were required to have experienced two or more relapses within the previous 2 years or one or more relapses in the year prior and/or had one gadolinium-enhancing lesion in the year prior to screening.

The study population was mostly from the Ukraine and Russia. It is more difficult to recruit patients into MS drug studies in the United States and Western Europe because many patients in these countries are already receiving approved drugs, which deters enrollment, explained Dr. Steinman.

Investigators randomly assigned the participants to receive the investigational drug or 14 mg of oral teriflunomide, a drug that blocks the proliferation of immune cells, once daily. The ublituximab group received an initial infusion of 150 mg over 4 hours and then a 1-hour infusion of 450 mg every 6 months over the course of the 96-week study.
 

Primary outcomes met

For ULTIMATE I, the primary outcome was ARR. Results showed that this rate was 0.076 for the ublituximab group and 0.188 for the teriflunomide group, resulting in a 60% relative reduction (adjusted ARR ratio, 0.406; 95% confidence interval, 0.268-0.615; P < .0001).

In ULTIMATE II, the ARR was 0.091 for ublituximab and 0.178 for teriflunomide, for a relative reduction of 49% (ARR ratio, 0.509; 95% CI, 0.330-0.784; P = .0022).

One way of interpreting these data is that patients are likely to have only one relapse in 10 years, said Dr. Steinman. “So that was very good news.”

It is not clear why relative reductions for ARR differed between the two studies; “probably the real number is somewhere between 60% and 49%,” Dr. Steinman said.

From MRI scans, the total number of relevant lesions was reduced by 97% with ublituximab compared with teriflunomide in ULTIMATE I and by 96% in trial II.

Another “piece of really good news” from the studies is that the drug led to a significant improvement in disability, rather than “just slowing it down,” Dr. Steinman noted.

There was a 116% increased chance of confirmed disability improvement (CDI) with ublituximab versus teriflunomide in the first trial (P = .003) and a 103% increased chance of CDI in the second trial (P = .0026).

The percentage of patients who had no evidence of disease activity was 198% for the patients who received the trial drug in comparison with the control group in trial I and 277% in trial II (P < .0001 for both trials).
 

A life changer?

Dr. Steinman said the “robust” findings suggest that patients with MS “won’t have a relapse and will improve. Those are two pretty good messages for somebody with this wretched disease.”

The investigational drug was generally well tolerated. The percentage of adverse events (AEs) with the study drug was about the same as with the comparator. About 9.5% of the ublituximab group had a serious AE, compared with 6.2% of the teriflunomide group.

The ublituximab group had more infections (4.0% vs. 2.6%), which Dr. Steinman said is not surprising because the drug is a potent immune suppressant. “It’s an unfortunate consequence of this kind of strong biologic that knocks down a whole arm of the immune system. The wonder to me is that these are still rather infrequent,” he said.

If approved, “it will be interesting to see how regulatory agencies handle this in terms of risk mitigation,” said Dr. Steinman. He added that a warning label might be a consideration.

However, the safety of this drug “is certainly acceptable,” said Dr. Steinman. “In general, this drug is not that different from the other drugs in the class of anti-CD20s.”

Dr. Steinman noted that he understands why some patients prefer an oral drug and may have an “aversion to getting stuck with a needle,” but he pointed out that teriflunomide has some drawbacks. For example, it tends to thin hair.

“For people who have had relapses, people who are unable to do what they want to in life – attend school, hold down jobs, exercise – this new drug could really be life changing,” he said.

He added that he would “strongly urge” his own family and relatives, if they had MS, to take one of the anti-CD20 drugs.

Ublituximab also has a number of advantages over the other agents in the same class. Not only does it work well, have an acceptable safety profile, and require a shorter infusion time, but it could also be less costly, Dr. Steinman noted. “The company has said it intends to come in at a lower price point,” he said.

The company is now planning to prepare a biological license application for use in MS. Interestingly, the drug, in combination with umbralisib (Ukoniq), is already under review by the FDA for use in chronic lymphoctytic leukemia and small lymphocytic lymphoma.
 

Striking improvement

When session chair Marcello Moccio, MD, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy, asked Dr. Steinman to elaborate on the “very strong effect” of the drug with regard to improving disability, Dr. Steinman said the improvement was “striking.”

Being able to talk to patients about possible improvement rather than about delaying disability “is really gratifying” and provides a “much more constructive and optimistic outlook,” he said.

He noted that as physicians improve their management of patients with MS “and are paying attention to things that we haven’t over the years, like vitamin D and even mental health,” disability progression management “is getting better.”

Dr. Steinman is a consultant for TG Therapeutics.

A version of this article first appeared on Medscape.com.

Clinicians who struggle to get dupilumab approved for their patients with moderate to severe atopic dermatitis (AD) are not alone.

Bruce Jancin/MDedge News

This scenario was illustrated in a 2020 retrospective study of 179 adults with AD who were cared for at the University of Pittsburgh Medical Center, which found that 37% did not start dupilumab, mainly due to insurance denial (19%) and high copay (11%).

“We’ve all seen this in our practice,” Amy S. Paller, MD, said during the Revolutionizing Atopic Dermatitis symposium. “We’ve also seen the denials until we get step therapy in there, so if I have a child whom I want to treat with dupilumab for safety reasons, I don’t like being told that I’m going to have to use cyclosporine or methotrexate or a medication that I think may have higher risks and certainly [would] require blood monitoring–yet that’s the state for some patients.”

Dupilumab, an interleukin-4 receptor alpha antagonist, is approved for treatment of moderate to severe AD in patients ages 6 and older.

When working to obtain insurance approval of dupilumab, Dr. Paller reminded dermatologists to document that the patient has moderate to severe AD “and document the negative effect on quality of life in order to try to help make it easier to get these medications for our patients.”
 

Starting patients on dupilumab

Dr. Paller, the Walter J. Hamlin Chair and Professor of Dermatology at Northwestern University, Chicago, said that if patients are on another systemic medication prior to starting dupilumab, she allows a transition period of 1-2 months. “Don’t just stop that drug because it’s ‘not working,’ ” she said. “I usually do a full dose for the first month, and a half dose for the next month before starting dupilumab. Also, don’t stop the use of topical corticosteroids. They can increase treatment response by 10%-20%, even when patients are on dupilumab.”

She recommends a 3- to 4-month trial of dupilumab while monitoring changes in disease severity, itch, and quality of life. “Usually there’s evidence of early improvement by 2 months in those who are going to do well enough to stay on the drug by about 4 months out,” she said. “In my experience, most pediatric patients do very well. In those with an inadequate response, about 50% will do better if you can increase the dose or frequency. Flares can still occur in those who do well. I usually push topicals when that happens.”

If patients respond well after starting dupilumab, Dr. Paller recommends that they continue on the drug for at least a year before considering a taper with the hope of “resetting” the immune system and having sustained improvement off drug. “Some parents and patients don’t want to stop the drug,” but for those who do, she tells them that she does not want to abruptly stop treatment, but to “space out the dosing” instead. “If someone is pretty much clear with the medication and is able to continue with topicals as you dial down, that’s great. But don’t even think about taking them off if somebody’s not clear or virtually clear, particularly if they start to flare with lower frequency.”
 

Data on effectiveness

Real-world data suggest that the effectiveness of dupilumab is similar to the efficacy seen in clinical trials. For example, a recently published systematic review and meta-analysis of 3,303 AD patients on dupilumab found that after 16 weeks of therapy, 60% achieved a 75% improvement in the Eczema Area and Severity (EASI75) score, and 27% achieved an EASI90. In a Dutch study of 210 adults treated with dupilumab for 52 weeks, enrolled in a Dutch registry, the mean percent reduction in EASI score was 70% at 16 weeks and 76.6% by 52 weeks.

In addition, there was at least a 4-point improvement in the Patient-Oriented Eczema Measure (POEM) score and at least a 4-point improvement in the Itch Numeric Rating Scale (NRS), said Dr. Paller, who was not involved in the study. “These patient-reported improvements were seen very early on,” she noted.

What about drug survival at 1 year? In a retrospective cohort study that drew from insurance databases, 1,963 adults given dupilumab were studied for a mean of 315 days. The rate of persistence was 92% at 6 months and 77% at 12 months. “That means that it’s still effective,” Dr. Paller said.

While that is a short period of time, she compared these results with long-term survival of nonsteroid systemic immunosuppressants such as cyclosporine, referring to a study of adults with AD treated with systemic immunosuppressants, which found “a 32% persistence rate at 12 months in drugs that require more monitoring, so more burden.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for dupilumab (Dupixent) manufacturers Regeneron and Sanofi, AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, and RAPT Therapeutics.

Clinicians who struggle to get dupilumab approved for their patients with moderate to severe atopic dermatitis (AD) are not alone.

Bruce Jancin/MDedge News

This scenario was illustrated in a 2020 retrospective study of 179 adults with AD who were cared for at the University of Pittsburgh Medical Center, which found that 37% did not start dupilumab, mainly due to insurance denial (19%) and high copay (11%).

“We’ve all seen this in our practice,” Amy S. Paller, MD, said during the Revolutionizing Atopic Dermatitis symposium. “We’ve also seen the denials until we get step therapy in there, so if I have a child whom I want to treat with dupilumab for safety reasons, I don’t like being told that I’m going to have to use cyclosporine or methotrexate or a medication that I think may have higher risks and certainly [would] require blood monitoring–yet that’s the state for some patients.”

Dupilumab, an interleukin-4 receptor alpha antagonist, is approved for treatment of moderate to severe AD in patients ages 6 and older.

When working to obtain insurance approval of dupilumab, Dr. Paller reminded dermatologists to document that the patient has moderate to severe AD “and document the negative effect on quality of life in order to try to help make it easier to get these medications for our patients.”
 

Starting patients on dupilumab

Dr. Paller, the Walter J. Hamlin Chair and Professor of Dermatology at Northwestern University, Chicago, said that if patients are on another systemic medication prior to starting dupilumab, she allows a transition period of 1-2 months. “Don’t just stop that drug because it’s ‘not working,’ ” she said. “I usually do a full dose for the first month, and a half dose for the next month before starting dupilumab. Also, don’t stop the use of topical corticosteroids. They can increase treatment response by 10%-20%, even when patients are on dupilumab.”

She recommends a 3- to 4-month trial of dupilumab while monitoring changes in disease severity, itch, and quality of life. “Usually there’s evidence of early improvement by 2 months in those who are going to do well enough to stay on the drug by about 4 months out,” she said. “In my experience, most pediatric patients do very well. In those with an inadequate response, about 50% will do better if you can increase the dose or frequency. Flares can still occur in those who do well. I usually push topicals when that happens.”

If patients respond well after starting dupilumab, Dr. Paller recommends that they continue on the drug for at least a year before considering a taper with the hope of “resetting” the immune system and having sustained improvement off drug. “Some parents and patients don’t want to stop the drug,” but for those who do, she tells them that she does not want to abruptly stop treatment, but to “space out the dosing” instead. “If someone is pretty much clear with the medication and is able to continue with topicals as you dial down, that’s great. But don’t even think about taking them off if somebody’s not clear or virtually clear, particularly if they start to flare with lower frequency.”
 

Data on effectiveness

Real-world data suggest that the effectiveness of dupilumab is similar to the efficacy seen in clinical trials. For example, a recently published systematic review and meta-analysis of 3,303 AD patients on dupilumab found that after 16 weeks of therapy, 60% achieved a 75% improvement in the Eczema Area and Severity (EASI75) score, and 27% achieved an EASI90. In a Dutch study of 210 adults treated with dupilumab for 52 weeks, enrolled in a Dutch registry, the mean percent reduction in EASI score was 70% at 16 weeks and 76.6% by 52 weeks.

In addition, there was at least a 4-point improvement in the Patient-Oriented Eczema Measure (POEM) score and at least a 4-point improvement in the Itch Numeric Rating Scale (NRS), said Dr. Paller, who was not involved in the study. “These patient-reported improvements were seen very early on,” she noted.

What about drug survival at 1 year? In a retrospective cohort study that drew from insurance databases, 1,963 adults given dupilumab were studied for a mean of 315 days. The rate of persistence was 92% at 6 months and 77% at 12 months. “That means that it’s still effective,” Dr. Paller said.

While that is a short period of time, she compared these results with long-term survival of nonsteroid systemic immunosuppressants such as cyclosporine, referring to a study of adults with AD treated with systemic immunosuppressants, which found “a 32% persistence rate at 12 months in drugs that require more monitoring, so more burden.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for dupilumab (Dupixent) manufacturers Regeneron and Sanofi, AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, and RAPT Therapeutics.

Clinicians who struggle to get dupilumab approved for their patients with moderate to severe atopic dermatitis (AD) are not alone.

Bruce Jancin/MDedge News

This scenario was illustrated in a 2020 retrospective study of 179 adults with AD who were cared for at the University of Pittsburgh Medical Center, which found that 37% did not start dupilumab, mainly due to insurance denial (19%) and high copay (11%).

“We’ve all seen this in our practice,” Amy S. Paller, MD, said during the Revolutionizing Atopic Dermatitis symposium. “We’ve also seen the denials until we get step therapy in there, so if I have a child whom I want to treat with dupilumab for safety reasons, I don’t like being told that I’m going to have to use cyclosporine or methotrexate or a medication that I think may have higher risks and certainly [would] require blood monitoring–yet that’s the state for some patients.”

Dupilumab, an interleukin-4 receptor alpha antagonist, is approved for treatment of moderate to severe AD in patients ages 6 and older.

When working to obtain insurance approval of dupilumab, Dr. Paller reminded dermatologists to document that the patient has moderate to severe AD “and document the negative effect on quality of life in order to try to help make it easier to get these medications for our patients.”
 

Starting patients on dupilumab

Dr. Paller, the Walter J. Hamlin Chair and Professor of Dermatology at Northwestern University, Chicago, said that if patients are on another systemic medication prior to starting dupilumab, she allows a transition period of 1-2 months. “Don’t just stop that drug because it’s ‘not working,’ ” she said. “I usually do a full dose for the first month, and a half dose for the next month before starting dupilumab. Also, don’t stop the use of topical corticosteroids. They can increase treatment response by 10%-20%, even when patients are on dupilumab.”

She recommends a 3- to 4-month trial of dupilumab while monitoring changes in disease severity, itch, and quality of life. “Usually there’s evidence of early improvement by 2 months in those who are going to do well enough to stay on the drug by about 4 months out,” she said. “In my experience, most pediatric patients do very well. In those with an inadequate response, about 50% will do better if you can increase the dose or frequency. Flares can still occur in those who do well. I usually push topicals when that happens.”

If patients respond well after starting dupilumab, Dr. Paller recommends that they continue on the drug for at least a year before considering a taper with the hope of “resetting” the immune system and having sustained improvement off drug. “Some parents and patients don’t want to stop the drug,” but for those who do, she tells them that she does not want to abruptly stop treatment, but to “space out the dosing” instead. “If someone is pretty much clear with the medication and is able to continue with topicals as you dial down, that’s great. But don’t even think about taking them off if somebody’s not clear or virtually clear, particularly if they start to flare with lower frequency.”
 

Data on effectiveness

Real-world data suggest that the effectiveness of dupilumab is similar to the efficacy seen in clinical trials. For example, a recently published systematic review and meta-analysis of 3,303 AD patients on dupilumab found that after 16 weeks of therapy, 60% achieved a 75% improvement in the Eczema Area and Severity (EASI75) score, and 27% achieved an EASI90. In a Dutch study of 210 adults treated with dupilumab for 52 weeks, enrolled in a Dutch registry, the mean percent reduction in EASI score was 70% at 16 weeks and 76.6% by 52 weeks.

In addition, there was at least a 4-point improvement in the Patient-Oriented Eczema Measure (POEM) score and at least a 4-point improvement in the Itch Numeric Rating Scale (NRS), said Dr. Paller, who was not involved in the study. “These patient-reported improvements were seen very early on,” she noted.

What about drug survival at 1 year? In a retrospective cohort study that drew from insurance databases, 1,963 adults given dupilumab were studied for a mean of 315 days. The rate of persistence was 92% at 6 months and 77% at 12 months. “That means that it’s still effective,” Dr. Paller said.

While that is a short period of time, she compared these results with long-term survival of nonsteroid systemic immunosuppressants such as cyclosporine, referring to a study of adults with AD treated with systemic immunosuppressants, which found “a 32% persistence rate at 12 months in drugs that require more monitoring, so more burden.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for dupilumab (Dupixent) manufacturers Regeneron and Sanofi, AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, and RAPT Therapeutics.

Obesity hypoventilation syndrome (OHS) is bound to be increasing because of the rising obesity epidemic but is underrecognized and “frequently underdiagnosed,” Saiprakash B. Venkateshiah, MD, said at the virtual annual meeting of the Associated Professional Sleep Societies.

The condition, which can cause significant morbidity and mortality, is defined by the combination of obesity and awake alveolar hypoventilation (PaCO₂ ≥45 mm Hg), with the exclusion of alternate causes of hypoventilation. Sleep-disordered breathing (SDB) is almost universally present, with approximately 90% of individuals with OHS also having obstructive sleep apnea (OSA), most often severe, and approximately 10% having sleep-related hypoventilation, or a “pure hypoventilation subtype, if you will,” said Dr. Venkateshiah, assistant professor of medicine at Emory University, Atlanta.

The prevalence of OHS in the general population is unknown, but its prevalence in patients who present for the evaluation of SDB has ranged from 8%-20% across multiple studies, he said. Up to 40% of patients with OHS present for the first time with acute hypercapnic respiratory failure, which has an in-hospital mortality of 18%.

Postmenopausal women appear to have a higher prevalence, compared with premenopausal women and men, he noted, and women appear to be more likely than men to present with the clinical phenotype of OHS without associated OSA.

The arterial blood gas measurement needed to document alveolar hypoventilation and definitively diagnosis OHA is a “simple and economical test,” he said, “but it is logistically very difficult to obtain [these measurements] routinely in all patients in the clinic ... and is one of the reasons why OSH is underdiagnosed.”
 

Guideline advice

A practice guideline published in 2019 by the American Thoracic Society suggests that, for obese patients with SDB and a low to moderate probability of having OSH, a serum bicarbonate level be measured first. “In patients with serum bicarbonate less than 27 mmol/L, clinicians might forgo measuring PaCO₂, as the diagnosis in them is very unlikely,” Dr. Venkateshiah said, referring to the guideline. “In patients with a serum bicarbonate greater than 27, you might need to measure PaCO₂ to confirm or rule out the diagnosis of OHS.”

(Patients strongly suspected of having OHS, with more than a low to moderate probability – those in whom arterial blood gases should be measured – are “usually severely obese with typical signs and symptoms such as dyspnea, nocturia, lower-extremity edema, excessive daytime sleepiness, fatigue, loud disruptive snoring, witnessed apneas, as well as mild hypoxemia during wake and/or significant hypoxemia during sleep,” the ATS guideline says.)

The guideline panel considered the use of oxygen saturation measured with pulse oximetry during wakefulness to screen for OHS and decided to advise against it because of the paucity of evidence-based literature, Dr. Venkateshiah noted. (In making its five conditional recommendations, the guideline panel cited an overall very low quality of evidence.)

Symptoms of OHS overlap with those of OSA (for example, daytime hypersomnolence, witnessed apneas, loud snoring, and morning headaches), so “symptoms alone cannot be used to discriminate between the two disorders,” he advised. Signs of OHS commonly seen in clinical exams, however, are low resting daytime oxygen saturations and lower-extremity edema. A sleep study, he added, is needed to document and characterize SDB in patients with OHS.

Positive airway pressure therapy is the first-line treatment for OHS, and long-term outcomes of patients with OHS on PAP treatment are significantly better, compared with untreated individuals. There is no strong evidence to recommend one form of PAP therapy over another for patients with OHS and concomitant severe OSA, he said, but “the bottom line” from both short- and long-term randomized clinical trials comparing CPAP with noninvasive ventilation “is that CPAP is equivalent to noninvasive ventilation as far as outcomes are concerned.”

The ATS guideline panel recommends continuous positive airway pressure therapy for patients with OHS and severe OSA. And for OHS with nonsevere OSA, bilevel PAP is traditionally used – including pure hypoventilators, Dr. Venkateshiah said.

Weight-loss interventions are paramount, since “the primary driver of OHS is obesity,” he said at the meeting. There are only a few studies that have looked at bariatric surgery in patients with OHS, he said, “but they did note significant improvements in gas exchange, sleep apnea, lung volumes and pulmonary hypertension.”

The ATS guideline suggests weight-loss interventions that produce sustained weight loss of 25%-30% of the actual body weight. Such interventions are “most likely required to achieve resolution of hypoventilation,” Dr. Venkateshiah said.
 

OHS vs. COPD

In a separate presentation on OHS, Michelle Cao, DO, clinical associate professor at Stanford (Calif.) University, emphasized the importance of distinguishing the patient with OHS from the patient with hypercapnic chronic obstructive pulmonary disease (COPD). Spirometry and the flow volume curve can help rule out hypercapnic COPD and other conditions that cause daytime hypoventilation.

A study published in 2016 of 600 hospitalized patients determined to have unequivocal OHS found that 43% had been misdiagnosed as having COPD and none had been previously diagnosed with OHS, Dr. Cao noted. Patients in the study had a mean age of 58 and a mean body mass index of 48.2 kg/m²; 64% were women.

Dr. Venkateshiah and Dr. Cao had no relevant disclosures.

Obesity hypoventilation syndrome (OHS) is bound to be increasing because of the rising obesity epidemic but is underrecognized and “frequently underdiagnosed,” Saiprakash B. Venkateshiah, MD, said at the virtual annual meeting of the Associated Professional Sleep Societies.

The condition, which can cause significant morbidity and mortality, is defined by the combination of obesity and awake alveolar hypoventilation (PaCO₂ ≥45 mm Hg), with the exclusion of alternate causes of hypoventilation. Sleep-disordered breathing (SDB) is almost universally present, with approximately 90% of individuals with OHS also having obstructive sleep apnea (OSA), most often severe, and approximately 10% having sleep-related hypoventilation, or a “pure hypoventilation subtype, if you will,” said Dr. Venkateshiah, assistant professor of medicine at Emory University, Atlanta.

The prevalence of OHS in the general population is unknown, but its prevalence in patients who present for the evaluation of SDB has ranged from 8%-20% across multiple studies, he said. Up to 40% of patients with OHS present for the first time with acute hypercapnic respiratory failure, which has an in-hospital mortality of 18%.

Postmenopausal women appear to have a higher prevalence, compared with premenopausal women and men, he noted, and women appear to be more likely than men to present with the clinical phenotype of OHS without associated OSA.

The arterial blood gas measurement needed to document alveolar hypoventilation and definitively diagnosis OHA is a “simple and economical test,” he said, “but it is logistically very difficult to obtain [these measurements] routinely in all patients in the clinic ... and is one of the reasons why OSH is underdiagnosed.”
 

Guideline advice

A practice guideline published in 2019 by the American Thoracic Society suggests that, for obese patients with SDB and a low to moderate probability of having OSH, a serum bicarbonate level be measured first. “In patients with serum bicarbonate less than 27 mmol/L, clinicians might forgo measuring PaCO₂, as the diagnosis in them is very unlikely,” Dr. Venkateshiah said, referring to the guideline. “In patients with a serum bicarbonate greater than 27, you might need to measure PaCO₂ to confirm or rule out the diagnosis of OHS.”

(Patients strongly suspected of having OHS, with more than a low to moderate probability – those in whom arterial blood gases should be measured – are “usually severely obese with typical signs and symptoms such as dyspnea, nocturia, lower-extremity edema, excessive daytime sleepiness, fatigue, loud disruptive snoring, witnessed apneas, as well as mild hypoxemia during wake and/or significant hypoxemia during sleep,” the ATS guideline says.)

The guideline panel considered the use of oxygen saturation measured with pulse oximetry during wakefulness to screen for OHS and decided to advise against it because of the paucity of evidence-based literature, Dr. Venkateshiah noted. (In making its five conditional recommendations, the guideline panel cited an overall very low quality of evidence.)

Symptoms of OHS overlap with those of OSA (for example, daytime hypersomnolence, witnessed apneas, loud snoring, and morning headaches), so “symptoms alone cannot be used to discriminate between the two disorders,” he advised. Signs of OHS commonly seen in clinical exams, however, are low resting daytime oxygen saturations and lower-extremity edema. A sleep study, he added, is needed to document and characterize SDB in patients with OHS.

Positive airway pressure therapy is the first-line treatment for OHS, and long-term outcomes of patients with OHS on PAP treatment are significantly better, compared with untreated individuals. There is no strong evidence to recommend one form of PAP therapy over another for patients with OHS and concomitant severe OSA, he said, but “the bottom line” from both short- and long-term randomized clinical trials comparing CPAP with noninvasive ventilation “is that CPAP is equivalent to noninvasive ventilation as far as outcomes are concerned.”

The ATS guideline panel recommends continuous positive airway pressure therapy for patients with OHS and severe OSA. And for OHS with nonsevere OSA, bilevel PAP is traditionally used – including pure hypoventilators, Dr. Venkateshiah said.

Weight-loss interventions are paramount, since “the primary driver of OHS is obesity,” he said at the meeting. There are only a few studies that have looked at bariatric surgery in patients with OHS, he said, “but they did note significant improvements in gas exchange, sleep apnea, lung volumes and pulmonary hypertension.”

The ATS guideline suggests weight-loss interventions that produce sustained weight loss of 25%-30% of the actual body weight. Such interventions are “most likely required to achieve resolution of hypoventilation,” Dr. Venkateshiah said.
 

OHS vs. COPD

In a separate presentation on OHS, Michelle Cao, DO, clinical associate professor at Stanford (Calif.) University, emphasized the importance of distinguishing the patient with OHS from the patient with hypercapnic chronic obstructive pulmonary disease (COPD). Spirometry and the flow volume curve can help rule out hypercapnic COPD and other conditions that cause daytime hypoventilation.

A study published in 2016 of 600 hospitalized patients determined to have unequivocal OHS found that 43% had been misdiagnosed as having COPD and none had been previously diagnosed with OHS, Dr. Cao noted. Patients in the study had a mean age of 58 and a mean body mass index of 48.2 kg/m²; 64% were women.

Dr. Venkateshiah and Dr. Cao had no relevant disclosures.

Obesity hypoventilation syndrome (OHS) is bound to be increasing because of the rising obesity epidemic but is underrecognized and “frequently underdiagnosed,” Saiprakash B. Venkateshiah, MD, said at the virtual annual meeting of the Associated Professional Sleep Societies.

The condition, which can cause significant morbidity and mortality, is defined by the combination of obesity and awake alveolar hypoventilation (PaCO₂ ≥45 mm Hg), with the exclusion of alternate causes of hypoventilation. Sleep-disordered breathing (SDB) is almost universally present, with approximately 90% of individuals with OHS also having obstructive sleep apnea (OSA), most often severe, and approximately 10% having sleep-related hypoventilation, or a “pure hypoventilation subtype, if you will,” said Dr. Venkateshiah, assistant professor of medicine at Emory University, Atlanta.

The prevalence of OHS in the general population is unknown, but its prevalence in patients who present for the evaluation of SDB has ranged from 8%-20% across multiple studies, he said. Up to 40% of patients with OHS present for the first time with acute hypercapnic respiratory failure, which has an in-hospital mortality of 18%.

Postmenopausal women appear to have a higher prevalence, compared with premenopausal women and men, he noted, and women appear to be more likely than men to present with the clinical phenotype of OHS without associated OSA.

The arterial blood gas measurement needed to document alveolar hypoventilation and definitively diagnosis OHA is a “simple and economical test,” he said, “but it is logistically very difficult to obtain [these measurements] routinely in all patients in the clinic ... and is one of the reasons why OSH is underdiagnosed.”
 

Guideline advice

A practice guideline published in 2019 by the American Thoracic Society suggests that, for obese patients with SDB and a low to moderate probability of having OSH, a serum bicarbonate level be measured first. “In patients with serum bicarbonate less than 27 mmol/L, clinicians might forgo measuring PaCO₂, as the diagnosis in them is very unlikely,” Dr. Venkateshiah said, referring to the guideline. “In patients with a serum bicarbonate greater than 27, you might need to measure PaCO₂ to confirm or rule out the diagnosis of OHS.”

(Patients strongly suspected of having OHS, with more than a low to moderate probability – those in whom arterial blood gases should be measured – are “usually severely obese with typical signs and symptoms such as dyspnea, nocturia, lower-extremity edema, excessive daytime sleepiness, fatigue, loud disruptive snoring, witnessed apneas, as well as mild hypoxemia during wake and/or significant hypoxemia during sleep,” the ATS guideline says.)

The guideline panel considered the use of oxygen saturation measured with pulse oximetry during wakefulness to screen for OHS and decided to advise against it because of the paucity of evidence-based literature, Dr. Venkateshiah noted. (In making its five conditional recommendations, the guideline panel cited an overall very low quality of evidence.)

Symptoms of OHS overlap with those of OSA (for example, daytime hypersomnolence, witnessed apneas, loud snoring, and morning headaches), so “symptoms alone cannot be used to discriminate between the two disorders,” he advised. Signs of OHS commonly seen in clinical exams, however, are low resting daytime oxygen saturations and lower-extremity edema. A sleep study, he added, is needed to document and characterize SDB in patients with OHS.

Positive airway pressure therapy is the first-line treatment for OHS, and long-term outcomes of patients with OHS on PAP treatment are significantly better, compared with untreated individuals. There is no strong evidence to recommend one form of PAP therapy over another for patients with OHS and concomitant severe OSA, he said, but “the bottom line” from both short- and long-term randomized clinical trials comparing CPAP with noninvasive ventilation “is that CPAP is equivalent to noninvasive ventilation as far as outcomes are concerned.”

The ATS guideline panel recommends continuous positive airway pressure therapy for patients with OHS and severe OSA. And for OHS with nonsevere OSA, bilevel PAP is traditionally used – including pure hypoventilators, Dr. Venkateshiah said.

Weight-loss interventions are paramount, since “the primary driver of OHS is obesity,” he said at the meeting. There are only a few studies that have looked at bariatric surgery in patients with OHS, he said, “but they did note significant improvements in gas exchange, sleep apnea, lung volumes and pulmonary hypertension.”

The ATS guideline suggests weight-loss interventions that produce sustained weight loss of 25%-30% of the actual body weight. Such interventions are “most likely required to achieve resolution of hypoventilation,” Dr. Venkateshiah said.
 

OHS vs. COPD

In a separate presentation on OHS, Michelle Cao, DO, clinical associate professor at Stanford (Calif.) University, emphasized the importance of distinguishing the patient with OHS from the patient with hypercapnic chronic obstructive pulmonary disease (COPD). Spirometry and the flow volume curve can help rule out hypercapnic COPD and other conditions that cause daytime hypoventilation.

A study published in 2016 of 600 hospitalized patients determined to have unequivocal OHS found that 43% had been misdiagnosed as having COPD and none had been previously diagnosed with OHS, Dr. Cao noted. Patients in the study had a mean age of 58 and a mean body mass index of 48.2 kg/m²; 64% were women.

Dr. Venkateshiah and Dr. Cao had no relevant disclosures.

The contraceptive needs of women who have had in vitro fertilization (IVF) pregnancies are real but are being overlooked, according to study data presented at the Royal College of Obstetricians & Gynaecologists (RCOG) Virtual World Congress 2021.

The interview-based study found that women report not being routinely informed about the chance of spontaneous pregnancy after IVF. “There is scope to follow-up with women after IVF … but information about the chances of spontaneous births and need for contraception isn’t given,” said lead researcher Annette Thwaites, MD, an academic clinical fellow and a senior registrar in Community Sexual and Reproductive Health at Kings College Hospital, London.

“Fertility services, maternity services, and community services could all do more to give women information on contraception postnatally,” Dr. Thwaites said.

“Even if a woman has had IVF previously, a woman shouldn’t lose the right to plan the rest of her family,” she added. “We need to stop shielding these women from the information they really do need.”

Dr. Thwaites first came across the issue around contraception after IVF pregnancy while talking to new mothers in a postnatal ward for another study. Ward staff told her not to enter the rooms with women who had had IVF births, with the implication that these women would not need or want contraception.

With this in mind, Dr. Thwaites and colleagues aimed to better understand the contraceptive needs of women after successful IVF pregnancy to improve service delivery and prevent unplanned and rapid-repeat pregnancies after IVF.

The researchers interviewed 21 women who had spontaneous pregnancies after successful IVF. Participants were aged 35-50 years, the majority were White, British, professional, married for at least 10 years, and living in nuclear families.

Of the spontaneous post-IVF pregnancies in these women, outcomes included single (11) and multiple live births (1 twin), miscarriage (1), ectopic (1) termination of pregnancy (1), and three ongoing pregnancies.  

After IVF pregnancy, most women said that they used no contraception or ineffective contraception and had never had a conversation around contraception after IVF.

The women also reported that spontaneous pregnancy was shocking and not universally welcomed, and interpregnancy intervals were often short.

In addition, comments by these women suggested certain aspects of the IVF experience reinforced their perceptions of subfertility. One is quoted as saying, “It seemed to be this big failure if you were having IVF.” Another said, “It’s bad enough that I’m having to conceive my baby like this.”
 

An unmet need

In her 30 years of practice, Melanie Davies, MD, has seen many women who experience natural pregnancy after IVF. She agrees it is important to address these women’s contraceptive needs but stresses that it needs to be approached carefully.

“It can stir up sensitivities to discuss this issue after having an IVF pregnancy,” said Dr. Davies, a consultant obstetrician and gynecologist at University College London Hospitals, London. “I think many women genuinely think that contraception after IVF just doesn’t apply, but lots of women do have natural pregnancies after IVF. I think women do need this information, but we need to be aware of the sensitivities around this issue, so the way we deliver it is crucial.”

Gwenda Burns, chief executive of the National Patient Charity Fertility Network UK, which supports people before, during, and after fertility treatment, agrees that the process leading up to a successful IVF birth can have lasting effects.

“Fertility struggles and going through fertility treatment can put an enormous strain on both physical and mental health and can have a long-lasting impact,” Ms. Burns said when asked to comment on the new study.

“It is vital that patients receive the right support, guidance, and advice following treatment, including when natural conception may still be possible,” Ms. Burns continued.
 

Growing population

Given the increasing use of IVF in recent years, Dr. Thwaites said the importance of understanding and meeting the contraceptive needs of women post-IVF is increasingly important. Also, people are turning to it earlier and for other reasons, such as women in same sex relationships, single women, pre-implantation genetic testing, and surrogates.

“During the recruitment process for the current study, I came across women who said since their IVF pregnancies they had no idea what they should do about contraception,” Dr. Thwaites said.

But she empathizes with health care professionals too. “I genuinely feel that health care professionals just don’t know how to advise women in this setting, so they avoid the topic of contraception altogether with these women. They are concerned about making women feel awkward or upsetting them. In my experience, there is very little said about IVF and contraception in the same breath.”
 

Women believe subfertility always persists after IVF

Among participants in the study, the causes of the women’s subfertility were wide-ranging and included tubal, anovulatory, male factor, joint, and unexplained, the latter of which affects 25% of couples with fertility issues. In the cohort, women had taken up to 9 years to conceive their first child and one had a donor egg conception.

After IVF, the chance of pregnancy will depend on the reason for the couple’s subfertility. “Given that a huge number of patients these days have unexplained subfertility. This is when there is no absolute cause of infertility identified, and it might not prevent a pregnancy but slows it down,” Dr. Davies said in an interview. “Such couples still have a chance of natural pregnancy.”

Polycystic ovary syndrome as a cause of subfertility is often associated with improvement in fertility after IVF, Dr. Davies noted. “This can improve after a spontaneous pregnancy or after IVF, even if the IVF is not a success, and this is possibly due to needling the ovary.”

Dr. Thwaites added that challenging women’s perceptions of their subfertility is critical if headway is to be made on this topic. Many women have persistent views concerning their subfertility after successful IVF, which may be rooted in previous failed treatment; need for repeat cycles or intracytoplasmic sperm injection (ICSI); low numbers of eggs collected; poor quality embryos; and pregnancy complications, to note some of the most common reasons.

“So many [women] feel that they are very lucky to have had a pregnancy because their journey has been difficult. They might have had a successful pregnancy, but they still hold a sense of personal failure,” said Dr. Thwaites. “Even after spontaneous pregnancy some women said it was a miracle or freak event. [Yet two of these] women had two spontaneous pregnancies.”

Remarkably, even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low among participants.

As well as fixed beliefs concerning their subfertility, other barriers to contraception use included a lack of knowledge of likelihood of spontaneous pregnancy; lack of contraceptive experience; and inherent incentives towards shorter interpregnancy intervals (e.g., the convenience and privacy of undergoing further IVF while still on maternity leave and availability of frozen embryos).

Looking ahead, Dr. Thwaites says there is a clear need to link and/or expand the maternity services dataset to uncover the true rates of post-IVF spontaneous pregnancy.

Dr. Thwaites and Dr. Davies have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The contraceptive needs of women who have had in vitro fertilization (IVF) pregnancies are real but are being overlooked, according to study data presented at the Royal College of Obstetricians & Gynaecologists (RCOG) Virtual World Congress 2021.

The interview-based study found that women report not being routinely informed about the chance of spontaneous pregnancy after IVF. “There is scope to follow-up with women after IVF … but information about the chances of spontaneous births and need for contraception isn’t given,” said lead researcher Annette Thwaites, MD, an academic clinical fellow and a senior registrar in Community Sexual and Reproductive Health at Kings College Hospital, London.

“Fertility services, maternity services, and community services could all do more to give women information on contraception postnatally,” Dr. Thwaites said.

“Even if a woman has had IVF previously, a woman shouldn’t lose the right to plan the rest of her family,” she added. “We need to stop shielding these women from the information they really do need.”

Dr. Thwaites first came across the issue around contraception after IVF pregnancy while talking to new mothers in a postnatal ward for another study. Ward staff told her not to enter the rooms with women who had had IVF births, with the implication that these women would not need or want contraception.

With this in mind, Dr. Thwaites and colleagues aimed to better understand the contraceptive needs of women after successful IVF pregnancy to improve service delivery and prevent unplanned and rapid-repeat pregnancies after IVF.

The researchers interviewed 21 women who had spontaneous pregnancies after successful IVF. Participants were aged 35-50 years, the majority were White, British, professional, married for at least 10 years, and living in nuclear families.

Of the spontaneous post-IVF pregnancies in these women, outcomes included single (11) and multiple live births (1 twin), miscarriage (1), ectopic (1) termination of pregnancy (1), and three ongoing pregnancies.  

After IVF pregnancy, most women said that they used no contraception or ineffective contraception and had never had a conversation around contraception after IVF.

The women also reported that spontaneous pregnancy was shocking and not universally welcomed, and interpregnancy intervals were often short.

In addition, comments by these women suggested certain aspects of the IVF experience reinforced their perceptions of subfertility. One is quoted as saying, “It seemed to be this big failure if you were having IVF.” Another said, “It’s bad enough that I’m having to conceive my baby like this.”
 

An unmet need

In her 30 years of practice, Melanie Davies, MD, has seen many women who experience natural pregnancy after IVF. She agrees it is important to address these women’s contraceptive needs but stresses that it needs to be approached carefully.

“It can stir up sensitivities to discuss this issue after having an IVF pregnancy,” said Dr. Davies, a consultant obstetrician and gynecologist at University College London Hospitals, London. “I think many women genuinely think that contraception after IVF just doesn’t apply, but lots of women do have natural pregnancies after IVF. I think women do need this information, but we need to be aware of the sensitivities around this issue, so the way we deliver it is crucial.”

Gwenda Burns, chief executive of the National Patient Charity Fertility Network UK, which supports people before, during, and after fertility treatment, agrees that the process leading up to a successful IVF birth can have lasting effects.

“Fertility struggles and going through fertility treatment can put an enormous strain on both physical and mental health and can have a long-lasting impact,” Ms. Burns said when asked to comment on the new study.

“It is vital that patients receive the right support, guidance, and advice following treatment, including when natural conception may still be possible,” Ms. Burns continued.
 

Growing population

Given the increasing use of IVF in recent years, Dr. Thwaites said the importance of understanding and meeting the contraceptive needs of women post-IVF is increasingly important. Also, people are turning to it earlier and for other reasons, such as women in same sex relationships, single women, pre-implantation genetic testing, and surrogates.

“During the recruitment process for the current study, I came across women who said since their IVF pregnancies they had no idea what they should do about contraception,” Dr. Thwaites said.

But she empathizes with health care professionals too. “I genuinely feel that health care professionals just don’t know how to advise women in this setting, so they avoid the topic of contraception altogether with these women. They are concerned about making women feel awkward or upsetting them. In my experience, there is very little said about IVF and contraception in the same breath.”
 

Women believe subfertility always persists after IVF

Among participants in the study, the causes of the women’s subfertility were wide-ranging and included tubal, anovulatory, male factor, joint, and unexplained, the latter of which affects 25% of couples with fertility issues. In the cohort, women had taken up to 9 years to conceive their first child and one had a donor egg conception.

After IVF, the chance of pregnancy will depend on the reason for the couple’s subfertility. “Given that a huge number of patients these days have unexplained subfertility. This is when there is no absolute cause of infertility identified, and it might not prevent a pregnancy but slows it down,” Dr. Davies said in an interview. “Such couples still have a chance of natural pregnancy.”

Polycystic ovary syndrome as a cause of subfertility is often associated with improvement in fertility after IVF, Dr. Davies noted. “This can improve after a spontaneous pregnancy or after IVF, even if the IVF is not a success, and this is possibly due to needling the ovary.”

Dr. Thwaites added that challenging women’s perceptions of their subfertility is critical if headway is to be made on this topic. Many women have persistent views concerning their subfertility after successful IVF, which may be rooted in previous failed treatment; need for repeat cycles or intracytoplasmic sperm injection (ICSI); low numbers of eggs collected; poor quality embryos; and pregnancy complications, to note some of the most common reasons.

“So many [women] feel that they are very lucky to have had a pregnancy because their journey has been difficult. They might have had a successful pregnancy, but they still hold a sense of personal failure,” said Dr. Thwaites. “Even after spontaneous pregnancy some women said it was a miracle or freak event. [Yet two of these] women had two spontaneous pregnancies.”

Remarkably, even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low among participants.

As well as fixed beliefs concerning their subfertility, other barriers to contraception use included a lack of knowledge of likelihood of spontaneous pregnancy; lack of contraceptive experience; and inherent incentives towards shorter interpregnancy intervals (e.g., the convenience and privacy of undergoing further IVF while still on maternity leave and availability of frozen embryos).

Looking ahead, Dr. Thwaites says there is a clear need to link and/or expand the maternity services dataset to uncover the true rates of post-IVF spontaneous pregnancy.

Dr. Thwaites and Dr. Davies have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The contraceptive needs of women who have had in vitro fertilization (IVF) pregnancies are real but are being overlooked, according to study data presented at the Royal College of Obstetricians & Gynaecologists (RCOG) Virtual World Congress 2021.

The interview-based study found that women report not being routinely informed about the chance of spontaneous pregnancy after IVF. “There is scope to follow-up with women after IVF … but information about the chances of spontaneous births and need for contraception isn’t given,” said lead researcher Annette Thwaites, MD, an academic clinical fellow and a senior registrar in Community Sexual and Reproductive Health at Kings College Hospital, London.

“Fertility services, maternity services, and community services could all do more to give women information on contraception postnatally,” Dr. Thwaites said.

“Even if a woman has had IVF previously, a woman shouldn’t lose the right to plan the rest of her family,” she added. “We need to stop shielding these women from the information they really do need.”

Dr. Thwaites first came across the issue around contraception after IVF pregnancy while talking to new mothers in a postnatal ward for another study. Ward staff told her not to enter the rooms with women who had had IVF births, with the implication that these women would not need or want contraception.

With this in mind, Dr. Thwaites and colleagues aimed to better understand the contraceptive needs of women after successful IVF pregnancy to improve service delivery and prevent unplanned and rapid-repeat pregnancies after IVF.

The researchers interviewed 21 women who had spontaneous pregnancies after successful IVF. Participants were aged 35-50 years, the majority were White, British, professional, married for at least 10 years, and living in nuclear families.

Of the spontaneous post-IVF pregnancies in these women, outcomes included single (11) and multiple live births (1 twin), miscarriage (1), ectopic (1) termination of pregnancy (1), and three ongoing pregnancies.  

After IVF pregnancy, most women said that they used no contraception or ineffective contraception and had never had a conversation around contraception after IVF.

The women also reported that spontaneous pregnancy was shocking and not universally welcomed, and interpregnancy intervals were often short.

In addition, comments by these women suggested certain aspects of the IVF experience reinforced their perceptions of subfertility. One is quoted as saying, “It seemed to be this big failure if you were having IVF.” Another said, “It’s bad enough that I’m having to conceive my baby like this.”
 

An unmet need

In her 30 years of practice, Melanie Davies, MD, has seen many women who experience natural pregnancy after IVF. She agrees it is important to address these women’s contraceptive needs but stresses that it needs to be approached carefully.

“It can stir up sensitivities to discuss this issue after having an IVF pregnancy,” said Dr. Davies, a consultant obstetrician and gynecologist at University College London Hospitals, London. “I think many women genuinely think that contraception after IVF just doesn’t apply, but lots of women do have natural pregnancies after IVF. I think women do need this information, but we need to be aware of the sensitivities around this issue, so the way we deliver it is crucial.”

Gwenda Burns, chief executive of the National Patient Charity Fertility Network UK, which supports people before, during, and after fertility treatment, agrees that the process leading up to a successful IVF birth can have lasting effects.

“Fertility struggles and going through fertility treatment can put an enormous strain on both physical and mental health and can have a long-lasting impact,” Ms. Burns said when asked to comment on the new study.

“It is vital that patients receive the right support, guidance, and advice following treatment, including when natural conception may still be possible,” Ms. Burns continued.
 

Growing population

Given the increasing use of IVF in recent years, Dr. Thwaites said the importance of understanding and meeting the contraceptive needs of women post-IVF is increasingly important. Also, people are turning to it earlier and for other reasons, such as women in same sex relationships, single women, pre-implantation genetic testing, and surrogates.

“During the recruitment process for the current study, I came across women who said since their IVF pregnancies they had no idea what they should do about contraception,” Dr. Thwaites said.

But she empathizes with health care professionals too. “I genuinely feel that health care professionals just don’t know how to advise women in this setting, so they avoid the topic of contraception altogether with these women. They are concerned about making women feel awkward or upsetting them. In my experience, there is very little said about IVF and contraception in the same breath.”
 

Women believe subfertility always persists after IVF

Among participants in the study, the causes of the women’s subfertility were wide-ranging and included tubal, anovulatory, male factor, joint, and unexplained, the latter of which affects 25% of couples with fertility issues. In the cohort, women had taken up to 9 years to conceive their first child and one had a donor egg conception.

After IVF, the chance of pregnancy will depend on the reason for the couple’s subfertility. “Given that a huge number of patients these days have unexplained subfertility. This is when there is no absolute cause of infertility identified, and it might not prevent a pregnancy but slows it down,” Dr. Davies said in an interview. “Such couples still have a chance of natural pregnancy.”

Polycystic ovary syndrome as a cause of subfertility is often associated with improvement in fertility after IVF, Dr. Davies noted. “This can improve after a spontaneous pregnancy or after IVF, even if the IVF is not a success, and this is possibly due to needling the ovary.”

Dr. Thwaites added that challenging women’s perceptions of their subfertility is critical if headway is to be made on this topic. Many women have persistent views concerning their subfertility after successful IVF, which may be rooted in previous failed treatment; need for repeat cycles or intracytoplasmic sperm injection (ICSI); low numbers of eggs collected; poor quality embryos; and pregnancy complications, to note some of the most common reasons.

“So many [women] feel that they are very lucky to have had a pregnancy because their journey has been difficult. They might have had a successful pregnancy, but they still hold a sense of personal failure,” said Dr. Thwaites. “Even after spontaneous pregnancy some women said it was a miracle or freak event. [Yet two of these] women had two spontaneous pregnancies.”

Remarkably, even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low among participants.

As well as fixed beliefs concerning their subfertility, other barriers to contraception use included a lack of knowledge of likelihood of spontaneous pregnancy; lack of contraceptive experience; and inherent incentives towards shorter interpregnancy intervals (e.g., the convenience and privacy of undergoing further IVF while still on maternity leave and availability of frozen embryos).

Looking ahead, Dr. Thwaites says there is a clear need to link and/or expand the maternity services dataset to uncover the true rates of post-IVF spontaneous pregnancy.

Dr. Thwaites and Dr. Davies have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A church-based diabetes self-management support intervention that incorporated parish nurses and peer leaders is feasible and may help improve diabetes-related outcomes in participants.

Sustained reductions in hemoglobin A1c and diabetes distress were seen in the Praise Diabetes Project, a 33-month study that piloted several different approaches to parish nurse and peer leader support at 21 urban churches in Michigan and Ohio, said Gretchen Piatt, MPH, PhD, associate professor in the department of learning health sciences at the University of Michigan, Ann Arbor, reported at the annual scientific sessions of the American Diabetes Association.

“Of the participants who achieved glycemic control following diabetes self-management education, a really large proportion – upward of 77% of participants across all the groups– achieved sustained glycemic control at 33 months,” Dr. Piatt said.

Findings from this study has helped diabetes educators better understand how to design effective support approaches that may have a long-term impact on glycemic control and diabetes distress, Dr. Piatt said.

The Praise Diabetes Project represents a “very smart strategy” of leveraging institutions that already exist in the African American community that are trusted and provide emotional support, said Tracey D. Brown, CEO of the ADA.

“This is about behavior change, really, at its crux,” Ms. Brown said in an interview. “To get there, you’ve got to have trust, and you have to have an emotional connection. If you don’t get either one of those things, then you really are not going to do anything in terms of changing behavior.”
 

Long-term solutions needed

Many studies show that diabetes self-management education can improve clinical and psychosocial outcomes, and reduce health care utilization and cost, at least in the short term, Dr. Piatt said. However, it’s less clear how those improvements can be sustained over longer periods of time.

“This then presents a critical need to develop and evaluate diabetes self-management support models that are ongoing, patient driven, and embedded within existing community infrastructures,” Dr. Piatt said in her presentation.

Working with churches is one approach to working within existing community infrastructures: “Churches are embedded in the community, they have the personnel oftentimes to facilitate these types of health programs, and most importantly, they have the established relationships with the community that brings about sustained changes,” Dr. Piatt said in her presentation.
 

Addressing diabetes education needs in urban, low-resource communities

The Praise Diabetes Project was a randomized, 33-month clinical trial conducted in 21 predominantly Black churches in Detroit; Flint, Mich.; and Toledo, Ohio, which are all urban, low-resource communities where diabetes is a significant public health problem, according to Dr. Piatt.

The study was designed to evaluate the relative effectiveness of three different approaches to diabetes self-management support at improving A1c and levels of diabetes distress, according to the investigators.

The churches were randomized to one of the support arms, including parish nurse plus peer leader support, parish nurse support by itself, or peer leader support by itself.

A total of 47 individuals were trained, including 31 peer leaders and 16 parish nurses.

All three interventions included an initial 6-month period of “enhanced usual care” during which biweekly newsletters that were distributed, according to Dr. Piatt. That was followed by 12 months of diabetes self-management support, and an additional 12 months of ongoing support facilitated by parish nurses and peer leaders on their own, without input from the research team or health care providers.

Participants in the program had to be at least 21 years old and under the care of a physician for their diabetes, according to Dr. Piatt. The parish nurses had to be registered nurses in Michigan or Ohio. Peer leaders had to be at least 21 years old, had at least an eighth-grade education, and had to commit to a 30-hour training program.

Peer leaders also had to be individuals living with diabetes: “Prior studies have found that, when peer leaders are actively working on their own self-management goals, they tend to be much more successful in helping others,” Dr. Piatt explained.

In addition to facilitating diabetes self-management education, the parish nurses and peer leaders in these interventions were responsible for recruitment, church announcements, room reservations, follow-up calls to participants, according to Dr. Piatt. Parish nurses also provided clinical content knowledge and supervised the peer leaders in the combined model.
 

Sustained reductions in A1c and diabetes distress

These diabetes self-management support approaches led to significant changes over time in A1c and diabetes distress, the primary outcomes of the study, Dr. Piatt said.

The peer leader support approach resulted in a statistically significant decline in A1c, from a mean of 8.0% at baseline to 7.7% at 33 months (P = .04), while nonsignificant declines were observed in the parish nurse and combined parish nurse–peer leader approach, according to the researcher.

Reductions in A1c persisted despite the COVID-19 pandemic, which began roughly 21 months into the study, she said.

Glycemic control remained steady over the course of the study, as illustrated by similar proportions of participants with A1c below 7% from baseline to 33 months, she added.

Sustained glycemic control was seen in all three groups, according to Dr. Piatt. For example, 42.7% of individuals in the parish nurse and peer leader support group achieved glycemic control following the intervention, and 88.5% of them sustained it at 33 months.

“I think this is one of the longest diabetes self-management education and diabetes self-management support interventions that’s out there right now, so we were so happy to see that sustained by glycemic control that far into the future,” she said.

Diabetes distress levels decreased steadily over time in all three groups, with declines that were statistically significant from baseline to 33 months in the parish nurse–only and peer leader–only groups, the investigator said.

The proportion of participants reporting moderate levels of diabetes distress dropped over time, especially in the peer leader support group, where there was a 50% reduction, she added.

Despite these findings, the study had limitations, according to Dr. Piatt, including some “burnout” that impacted participants, parish nurses, and peer leaders, especially after the pandemic started.

In addition, this type of intervention may have limited impact in the community at large: “We probably didn’t reach people who did not have good connection to the church,” Dr. Piatt said.

Dr. Piatt reported no conflicts of interest related to the research.

A church-based diabetes self-management support intervention that incorporated parish nurses and peer leaders is feasible and may help improve diabetes-related outcomes in participants.

Sustained reductions in hemoglobin A1c and diabetes distress were seen in the Praise Diabetes Project, a 33-month study that piloted several different approaches to parish nurse and peer leader support at 21 urban churches in Michigan and Ohio, said Gretchen Piatt, MPH, PhD, associate professor in the department of learning health sciences at the University of Michigan, Ann Arbor, reported at the annual scientific sessions of the American Diabetes Association.

“Of the participants who achieved glycemic control following diabetes self-management education, a really large proportion – upward of 77% of participants across all the groups– achieved sustained glycemic control at 33 months,” Dr. Piatt said.

Findings from this study has helped diabetes educators better understand how to design effective support approaches that may have a long-term impact on glycemic control and diabetes distress, Dr. Piatt said.

The Praise Diabetes Project represents a “very smart strategy” of leveraging institutions that already exist in the African American community that are trusted and provide emotional support, said Tracey D. Brown, CEO of the ADA.

“This is about behavior change, really, at its crux,” Ms. Brown said in an interview. “To get there, you’ve got to have trust, and you have to have an emotional connection. If you don’t get either one of those things, then you really are not going to do anything in terms of changing behavior.”
 

Long-term solutions needed

Many studies show that diabetes self-management education can improve clinical and psychosocial outcomes, and reduce health care utilization and cost, at least in the short term, Dr. Piatt said. However, it’s less clear how those improvements can be sustained over longer periods of time.

“This then presents a critical need to develop and evaluate diabetes self-management support models that are ongoing, patient driven, and embedded within existing community infrastructures,” Dr. Piatt said in her presentation.

Working with churches is one approach to working within existing community infrastructures: “Churches are embedded in the community, they have the personnel oftentimes to facilitate these types of health programs, and most importantly, they have the established relationships with the community that brings about sustained changes,” Dr. Piatt said in her presentation.
 

Addressing diabetes education needs in urban, low-resource communities

The Praise Diabetes Project was a randomized, 33-month clinical trial conducted in 21 predominantly Black churches in Detroit; Flint, Mich.; and Toledo, Ohio, which are all urban, low-resource communities where diabetes is a significant public health problem, according to Dr. Piatt.

The study was designed to evaluate the relative effectiveness of three different approaches to diabetes self-management support at improving A1c and levels of diabetes distress, according to the investigators.

The churches were randomized to one of the support arms, including parish nurse plus peer leader support, parish nurse support by itself, or peer leader support by itself.

A total of 47 individuals were trained, including 31 peer leaders and 16 parish nurses.

All three interventions included an initial 6-month period of “enhanced usual care” during which biweekly newsletters that were distributed, according to Dr. Piatt. That was followed by 12 months of diabetes self-management support, and an additional 12 months of ongoing support facilitated by parish nurses and peer leaders on their own, without input from the research team or health care providers.

Participants in the program had to be at least 21 years old and under the care of a physician for their diabetes, according to Dr. Piatt. The parish nurses had to be registered nurses in Michigan or Ohio. Peer leaders had to be at least 21 years old, had at least an eighth-grade education, and had to commit to a 30-hour training program.

Peer leaders also had to be individuals living with diabetes: “Prior studies have found that, when peer leaders are actively working on their own self-management goals, they tend to be much more successful in helping others,” Dr. Piatt explained.

In addition to facilitating diabetes self-management education, the parish nurses and peer leaders in these interventions were responsible for recruitment, church announcements, room reservations, follow-up calls to participants, according to Dr. Piatt. Parish nurses also provided clinical content knowledge and supervised the peer leaders in the combined model.
 

Sustained reductions in A1c and diabetes distress

These diabetes self-management support approaches led to significant changes over time in A1c and diabetes distress, the primary outcomes of the study, Dr. Piatt said.

The peer leader support approach resulted in a statistically significant decline in A1c, from a mean of 8.0% at baseline to 7.7% at 33 months (P = .04), while nonsignificant declines were observed in the parish nurse and combined parish nurse–peer leader approach, according to the researcher.

Reductions in A1c persisted despite the COVID-19 pandemic, which began roughly 21 months into the study, she said.

Glycemic control remained steady over the course of the study, as illustrated by similar proportions of participants with A1c below 7% from baseline to 33 months, she added.

Sustained glycemic control was seen in all three groups, according to Dr. Piatt. For example, 42.7% of individuals in the parish nurse and peer leader support group achieved glycemic control following the intervention, and 88.5% of them sustained it at 33 months.

“I think this is one of the longest diabetes self-management education and diabetes self-management support interventions that’s out there right now, so we were so happy to see that sustained by glycemic control that far into the future,” she said.

Diabetes distress levels decreased steadily over time in all three groups, with declines that were statistically significant from baseline to 33 months in the parish nurse–only and peer leader–only groups, the investigator said.

The proportion of participants reporting moderate levels of diabetes distress dropped over time, especially in the peer leader support group, where there was a 50% reduction, she added.

Despite these findings, the study had limitations, according to Dr. Piatt, including some “burnout” that impacted participants, parish nurses, and peer leaders, especially after the pandemic started.

In addition, this type of intervention may have limited impact in the community at large: “We probably didn’t reach people who did not have good connection to the church,” Dr. Piatt said.

Dr. Piatt reported no conflicts of interest related to the research.

A church-based diabetes self-management support intervention that incorporated parish nurses and peer leaders is feasible and may help improve diabetes-related outcomes in participants.

Sustained reductions in hemoglobin A1c and diabetes distress were seen in the Praise Diabetes Project, a 33-month study that piloted several different approaches to parish nurse and peer leader support at 21 urban churches in Michigan and Ohio, said Gretchen Piatt, MPH, PhD, associate professor in the department of learning health sciences at the University of Michigan, Ann Arbor, reported at the annual scientific sessions of the American Diabetes Association.

“Of the participants who achieved glycemic control following diabetes self-management education, a really large proportion – upward of 77% of participants across all the groups– achieved sustained glycemic control at 33 months,” Dr. Piatt said.

Findings from this study has helped diabetes educators better understand how to design effective support approaches that may have a long-term impact on glycemic control and diabetes distress, Dr. Piatt said.

The Praise Diabetes Project represents a “very smart strategy” of leveraging institutions that already exist in the African American community that are trusted and provide emotional support, said Tracey D. Brown, CEO of the ADA.

“This is about behavior change, really, at its crux,” Ms. Brown said in an interview. “To get there, you’ve got to have trust, and you have to have an emotional connection. If you don’t get either one of those things, then you really are not going to do anything in terms of changing behavior.”
 

Long-term solutions needed

Many studies show that diabetes self-management education can improve clinical and psychosocial outcomes, and reduce health care utilization and cost, at least in the short term, Dr. Piatt said. However, it’s less clear how those improvements can be sustained over longer periods of time.

“This then presents a critical need to develop and evaluate diabetes self-management support models that are ongoing, patient driven, and embedded within existing community infrastructures,” Dr. Piatt said in her presentation.

Working with churches is one approach to working within existing community infrastructures: “Churches are embedded in the community, they have the personnel oftentimes to facilitate these types of health programs, and most importantly, they have the established relationships with the community that brings about sustained changes,” Dr. Piatt said in her presentation.
 

Addressing diabetes education needs in urban, low-resource communities

The Praise Diabetes Project was a randomized, 33-month clinical trial conducted in 21 predominantly Black churches in Detroit; Flint, Mich.; and Toledo, Ohio, which are all urban, low-resource communities where diabetes is a significant public health problem, according to Dr. Piatt.

The study was designed to evaluate the relative effectiveness of three different approaches to diabetes self-management support at improving A1c and levels of diabetes distress, according to the investigators.

The churches were randomized to one of the support arms, including parish nurse plus peer leader support, parish nurse support by itself, or peer leader support by itself.

A total of 47 individuals were trained, including 31 peer leaders and 16 parish nurses.

All three interventions included an initial 6-month period of “enhanced usual care” during which biweekly newsletters that were distributed, according to Dr. Piatt. That was followed by 12 months of diabetes self-management support, and an additional 12 months of ongoing support facilitated by parish nurses and peer leaders on their own, without input from the research team or health care providers.

Participants in the program had to be at least 21 years old and under the care of a physician for their diabetes, according to Dr. Piatt. The parish nurses had to be registered nurses in Michigan or Ohio. Peer leaders had to be at least 21 years old, had at least an eighth-grade education, and had to commit to a 30-hour training program.

Peer leaders also had to be individuals living with diabetes: “Prior studies have found that, when peer leaders are actively working on their own self-management goals, they tend to be much more successful in helping others,” Dr. Piatt explained.

In addition to facilitating diabetes self-management education, the parish nurses and peer leaders in these interventions were responsible for recruitment, church announcements, room reservations, follow-up calls to participants, according to Dr. Piatt. Parish nurses also provided clinical content knowledge and supervised the peer leaders in the combined model.
 

Sustained reductions in A1c and diabetes distress

These diabetes self-management support approaches led to significant changes over time in A1c and diabetes distress, the primary outcomes of the study, Dr. Piatt said.

The peer leader support approach resulted in a statistically significant decline in A1c, from a mean of 8.0% at baseline to 7.7% at 33 months (P = .04), while nonsignificant declines were observed in the parish nurse and combined parish nurse–peer leader approach, according to the researcher.

Reductions in A1c persisted despite the COVID-19 pandemic, which began roughly 21 months into the study, she said.

Glycemic control remained steady over the course of the study, as illustrated by similar proportions of participants with A1c below 7% from baseline to 33 months, she added.

Sustained glycemic control was seen in all three groups, according to Dr. Piatt. For example, 42.7% of individuals in the parish nurse and peer leader support group achieved glycemic control following the intervention, and 88.5% of them sustained it at 33 months.

“I think this is one of the longest diabetes self-management education and diabetes self-management support interventions that’s out there right now, so we were so happy to see that sustained by glycemic control that far into the future,” she said.

Diabetes distress levels decreased steadily over time in all three groups, with declines that were statistically significant from baseline to 33 months in the parish nurse–only and peer leader–only groups, the investigator said.

The proportion of participants reporting moderate levels of diabetes distress dropped over time, especially in the peer leader support group, where there was a 50% reduction, she added.

Despite these findings, the study had limitations, according to Dr. Piatt, including some “burnout” that impacted participants, parish nurses, and peer leaders, especially after the pandemic started.

In addition, this type of intervention may have limited impact in the community at large: “We probably didn’t reach people who did not have good connection to the church,” Dr. Piatt said.

Dr. Piatt reported no conflicts of interest related to the research.