Conference Coverage

Twice-yearly injections are 100% effective in preventing new infections, according to the final results from the PURPOSE 1 trial of lenacapavir.

For weeks, the HIV community has been talking about this highly anticipated clinical trial and whether the strong — and to many, surprising — interim results would hold at final presentation at the International AIDS Conference 2024 in Munich, Germany.

Presenting the results, Linda-Gail Bekker, MD, director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, reported zero new infections in those who got the shots in the study of about 5000 young women. In the group given daily oral preexposure prophylaxis (PrEP), roughly 2% contracted HIV from infected partners.

“A twice-yearly PrEP choice could overcome some of the adherence and persistence challenges and contribute critically to our quest to reduce HIV infection in women around the world,” Dr. Bekker said about the results, which were published simultaneously in The New England Journal of Medicine.

PURPOSE 1 confirmed that lenacapavir is a “breakthrough” for HIV prevention, said International AIDS Society president Sharon Lewin, PhD, MBBS. It has “huge public health potential,” said Dr. Lewin, the AIDS 2024 conference cochair and director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia.

Lenacapavir is a novel, first-in-class multistage HIV-1 capsid inhibitor with a long half-life, which enables the twice-yearly dosing.

PURPOSE 1 enrolled women aged 15-25 years who were at risk for HIV in South Africa and Uganda, with a primary endpoint of HIV infection. Because of the previously announced interim results, which showed the injection was preventing infections, study sponsor Gilead Sciences discontinued the randomized phase of the trial and shifted to an open-label design for lenacapavir.

“One hundred percent efficacy is more that we could ever have hoped for a potential prevention efficacy,” said Christoph Spinner, MD, MBA, an infectious disease specialist at the University Hospital of the Technical University of Munich and AIDS 2024 conference cochair.

Dr. Spinner added that while this is the first study of lenacapavir for PrEP, it’s also the first to explore outcomes of emtricitabine-tenofovir in cisgender women.
 

Strong Adherence Rates

The twice-yearly injection demonstrated adherence rates above 90% in the trial for both the 6- and 12-month injection intervals.

“Adherence was 91.5% at week 26 and 92.8% at week 52,” Dr. Bekker reported. 

The trial compared three PrEP options including the lenacapavir injection to once-daily oral emtricitabine 200 mg and tenofovir-alafenamide 25 mg (F/TAF) and once-daily emtricitabine 200 mg and tenofovir–disoproxil fumarate 300 mg (F/TDF).

“Most participants in both the F/TAF and F/TDF groups had low adherence, and this declined over time,” Dr. Bekker reported. At 52 weeks, the vast majority of patients on both oral therapies had low adherence with dosing, defined at less than two doses a week.

Dr. Bekker called the adherence to the oral agents in this trial “disappointing.”

Findings from the trial underscore the challenges of adherence to a daily oral medication, Rochelle Walensky, MD, and Lindsey Baden, MD, from the Harvard Kennedy School of Government and Harvard Business School in Cambridge, Massachusetts, wrote in an editorial accompanying the published results.

With almost 92% attendance for the twice-yearly lenacapavir injections, the “well-done,” large, randomized, controlled trial “exemplifies not only that women can dependably adhere to this administration schedule, but also that levels of an HIV-1 capsid inhibitor can remain high enough over a period of 6 months to reliably prevent infection,” they added. 

Another key focus of the presentation was adverse events. The rate of adverse events grade 3 or more in the lenacapavir arm was 4.1%, Bekker said, which is slightly lower than the rates in the oral arms. The rates of serious adverse events were 2.8% for lenacapavir, 4% for F/TAF and 3.3% for F/TDF. 
 

Injection Site Reactions

Injection site reactions occurred in 68% of the lenacapavir group, including 63% with subcutaneous nodules.

The injection can form “a drug depot which may be palpable as a nodule,” Dr. Bekker said. In the placebo group, 34% of patients had injection-site reactions and 16% had nodules. Nearly all injection-site reactions were grade 1 or 2, she said. “Higher grade injection-site reactions were rare and not serious and occurred in a similar percentage in lenacapavir and placebo,” she said.

Overall, more than 25,000 injections of lenacapavir have been given, Dr. Bekker said, and four patients discontinued treatment because of injection-site reactions. “Reporting of injection-site reactions, including nodules, decreased with subsequent doses,” she said.

Contraception was not a requirement for enrollment in the study, Dr. Bekker pointed out, and pregnancy outcomes across the treatment arms were similar to the general population.
 

First in a Series of Trials

This is the first in a series of PURPOSE trials, Bekker reported. The phase 3 PURPOSE 2 trial, enrolling 3000 gay men, transgender women, transgender men and gender nonbinary people who have sex with male partners, is the second pivotal trial now underway.

Three other smaller trials are in the clinic in the United States and Europe.

PURPOSE 1 participants will continue to access lenacapavir until the product is available in South Africa and Uganda, Dr. Bekker said. Trial sponsor Gilead Sciences is also developing a direct licensing program to expedite generic access to the drug in high-incidence, resource-limited countries, she said.

Dr. Walensky and Dr. Baden report that lenacapavir currently costs about $43,000 annually in the United States. “But the results of the PURPOSE 1 trial have now created a moral imperative to make lenacapavir broadly accessible and affordable as PrEP” to people who were enrolled, as well as all those who are similarly eligible and could benefit.

So now we have a PrEP product with high efficacy, they added. “That is great news for science but not (yet) great for women.” 

Given the high pregnancy rate among participants in the PURPOSE 1 trial, Dr. Walensky and Dr. Baden point out the assessment of lenacapavir safety is a priority. They are also interested in learning more about drug resistance with this new option. 

“I f approved and delivered — rapidly, affordably, and equitably — to those who need or want it, this long-acting tool could help accelerate global progress in HIV prevention,” Dr. Lewin said.

Now, she added, “we eagerly await results from PURPOSE 2.”
 

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

Twice-yearly injections are 100% effective in preventing new infections, according to the final results from the PURPOSE 1 trial of lenacapavir.

For weeks, the HIV community has been talking about this highly anticipated clinical trial and whether the strong — and to many, surprising — interim results would hold at final presentation at the International AIDS Conference 2024 in Munich, Germany.

Presenting the results, Linda-Gail Bekker, MD, director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, reported zero new infections in those who got the shots in the study of about 5000 young women. In the group given daily oral preexposure prophylaxis (PrEP), roughly 2% contracted HIV from infected partners.

“A twice-yearly PrEP choice could overcome some of the adherence and persistence challenges and contribute critically to our quest to reduce HIV infection in women around the world,” Dr. Bekker said about the results, which were published simultaneously in The New England Journal of Medicine.

PURPOSE 1 confirmed that lenacapavir is a “breakthrough” for HIV prevention, said International AIDS Society president Sharon Lewin, PhD, MBBS. It has “huge public health potential,” said Dr. Lewin, the AIDS 2024 conference cochair and director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia.

Lenacapavir is a novel, first-in-class multistage HIV-1 capsid inhibitor with a long half-life, which enables the twice-yearly dosing.

PURPOSE 1 enrolled women aged 15-25 years who were at risk for HIV in South Africa and Uganda, with a primary endpoint of HIV infection. Because of the previously announced interim results, which showed the injection was preventing infections, study sponsor Gilead Sciences discontinued the randomized phase of the trial and shifted to an open-label design for lenacapavir.

“One hundred percent efficacy is more that we could ever have hoped for a potential prevention efficacy,” said Christoph Spinner, MD, MBA, an infectious disease specialist at the University Hospital of the Technical University of Munich and AIDS 2024 conference cochair.

Dr. Spinner added that while this is the first study of lenacapavir for PrEP, it’s also the first to explore outcomes of emtricitabine-tenofovir in cisgender women.
 

Strong Adherence Rates

The twice-yearly injection demonstrated adherence rates above 90% in the trial for both the 6- and 12-month injection intervals.

“Adherence was 91.5% at week 26 and 92.8% at week 52,” Dr. Bekker reported. 

The trial compared three PrEP options including the lenacapavir injection to once-daily oral emtricitabine 200 mg and tenofovir-alafenamide 25 mg (F/TAF) and once-daily emtricitabine 200 mg and tenofovir–disoproxil fumarate 300 mg (F/TDF).

“Most participants in both the F/TAF and F/TDF groups had low adherence, and this declined over time,” Dr. Bekker reported. At 52 weeks, the vast majority of patients on both oral therapies had low adherence with dosing, defined at less than two doses a week.

Dr. Bekker called the adherence to the oral agents in this trial “disappointing.”

Findings from the trial underscore the challenges of adherence to a daily oral medication, Rochelle Walensky, MD, and Lindsey Baden, MD, from the Harvard Kennedy School of Government and Harvard Business School in Cambridge, Massachusetts, wrote in an editorial accompanying the published results.

With almost 92% attendance for the twice-yearly lenacapavir injections, the “well-done,” large, randomized, controlled trial “exemplifies not only that women can dependably adhere to this administration schedule, but also that levels of an HIV-1 capsid inhibitor can remain high enough over a period of 6 months to reliably prevent infection,” they added. 

Another key focus of the presentation was adverse events. The rate of adverse events grade 3 or more in the lenacapavir arm was 4.1%, Bekker said, which is slightly lower than the rates in the oral arms. The rates of serious adverse events were 2.8% for lenacapavir, 4% for F/TAF and 3.3% for F/TDF. 
 

Injection Site Reactions

Injection site reactions occurred in 68% of the lenacapavir group, including 63% with subcutaneous nodules.

The injection can form “a drug depot which may be palpable as a nodule,” Dr. Bekker said. In the placebo group, 34% of patients had injection-site reactions and 16% had nodules. Nearly all injection-site reactions were grade 1 or 2, she said. “Higher grade injection-site reactions were rare and not serious and occurred in a similar percentage in lenacapavir and placebo,” she said.

Overall, more than 25,000 injections of lenacapavir have been given, Dr. Bekker said, and four patients discontinued treatment because of injection-site reactions. “Reporting of injection-site reactions, including nodules, decreased with subsequent doses,” she said.

Contraception was not a requirement for enrollment in the study, Dr. Bekker pointed out, and pregnancy outcomes across the treatment arms were similar to the general population.
 

First in a Series of Trials

This is the first in a series of PURPOSE trials, Bekker reported. The phase 3 PURPOSE 2 trial, enrolling 3000 gay men, transgender women, transgender men and gender nonbinary people who have sex with male partners, is the second pivotal trial now underway.

Three other smaller trials are in the clinic in the United States and Europe.

PURPOSE 1 participants will continue to access lenacapavir until the product is available in South Africa and Uganda, Dr. Bekker said. Trial sponsor Gilead Sciences is also developing a direct licensing program to expedite generic access to the drug in high-incidence, resource-limited countries, she said.

Dr. Walensky and Dr. Baden report that lenacapavir currently costs about $43,000 annually in the United States. “But the results of the PURPOSE 1 trial have now created a moral imperative to make lenacapavir broadly accessible and affordable as PrEP” to people who were enrolled, as well as all those who are similarly eligible and could benefit.

So now we have a PrEP product with high efficacy, they added. “That is great news for science but not (yet) great for women.” 

Given the high pregnancy rate among participants in the PURPOSE 1 trial, Dr. Walensky and Dr. Baden point out the assessment of lenacapavir safety is a priority. They are also interested in learning more about drug resistance with this new option. 

“I f approved and delivered — rapidly, affordably, and equitably — to those who need or want it, this long-acting tool could help accelerate global progress in HIV prevention,” Dr. Lewin said.

Now, she added, “we eagerly await results from PURPOSE 2.”
 

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

Twice-yearly injections are 100% effective in preventing new infections, according to the final results from the PURPOSE 1 trial of lenacapavir.

For weeks, the HIV community has been talking about this highly anticipated clinical trial and whether the strong — and to many, surprising — interim results would hold at final presentation at the International AIDS Conference 2024 in Munich, Germany.

Presenting the results, Linda-Gail Bekker, MD, director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, reported zero new infections in those who got the shots in the study of about 5000 young women. In the group given daily oral preexposure prophylaxis (PrEP), roughly 2% contracted HIV from infected partners.

“A twice-yearly PrEP choice could overcome some of the adherence and persistence challenges and contribute critically to our quest to reduce HIV infection in women around the world,” Dr. Bekker said about the results, which were published simultaneously in The New England Journal of Medicine.

PURPOSE 1 confirmed that lenacapavir is a “breakthrough” for HIV prevention, said International AIDS Society president Sharon Lewin, PhD, MBBS. It has “huge public health potential,” said Dr. Lewin, the AIDS 2024 conference cochair and director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia.

Lenacapavir is a novel, first-in-class multistage HIV-1 capsid inhibitor with a long half-life, which enables the twice-yearly dosing.

PURPOSE 1 enrolled women aged 15-25 years who were at risk for HIV in South Africa and Uganda, with a primary endpoint of HIV infection. Because of the previously announced interim results, which showed the injection was preventing infections, study sponsor Gilead Sciences discontinued the randomized phase of the trial and shifted to an open-label design for lenacapavir.

“One hundred percent efficacy is more that we could ever have hoped for a potential prevention efficacy,” said Christoph Spinner, MD, MBA, an infectious disease specialist at the University Hospital of the Technical University of Munich and AIDS 2024 conference cochair.

Dr. Spinner added that while this is the first study of lenacapavir for PrEP, it’s also the first to explore outcomes of emtricitabine-tenofovir in cisgender women.
 

Strong Adherence Rates

The twice-yearly injection demonstrated adherence rates above 90% in the trial for both the 6- and 12-month injection intervals.

“Adherence was 91.5% at week 26 and 92.8% at week 52,” Dr. Bekker reported. 

The trial compared three PrEP options including the lenacapavir injection to once-daily oral emtricitabine 200 mg and tenofovir-alafenamide 25 mg (F/TAF) and once-daily emtricitabine 200 mg and tenofovir–disoproxil fumarate 300 mg (F/TDF).

“Most participants in both the F/TAF and F/TDF groups had low adherence, and this declined over time,” Dr. Bekker reported. At 52 weeks, the vast majority of patients on both oral therapies had low adherence with dosing, defined at less than two doses a week.

Dr. Bekker called the adherence to the oral agents in this trial “disappointing.”

Findings from the trial underscore the challenges of adherence to a daily oral medication, Rochelle Walensky, MD, and Lindsey Baden, MD, from the Harvard Kennedy School of Government and Harvard Business School in Cambridge, Massachusetts, wrote in an editorial accompanying the published results.

With almost 92% attendance for the twice-yearly lenacapavir injections, the “well-done,” large, randomized, controlled trial “exemplifies not only that women can dependably adhere to this administration schedule, but also that levels of an HIV-1 capsid inhibitor can remain high enough over a period of 6 months to reliably prevent infection,” they added. 

Another key focus of the presentation was adverse events. The rate of adverse events grade 3 or more in the lenacapavir arm was 4.1%, Bekker said, which is slightly lower than the rates in the oral arms. The rates of serious adverse events were 2.8% for lenacapavir, 4% for F/TAF and 3.3% for F/TDF. 
 

Injection Site Reactions

Injection site reactions occurred in 68% of the lenacapavir group, including 63% with subcutaneous nodules.

The injection can form “a drug depot which may be palpable as a nodule,” Dr. Bekker said. In the placebo group, 34% of patients had injection-site reactions and 16% had nodules. Nearly all injection-site reactions were grade 1 or 2, she said. “Higher grade injection-site reactions were rare and not serious and occurred in a similar percentage in lenacapavir and placebo,” she said.

Overall, more than 25,000 injections of lenacapavir have been given, Dr. Bekker said, and four patients discontinued treatment because of injection-site reactions. “Reporting of injection-site reactions, including nodules, decreased with subsequent doses,” she said.

Contraception was not a requirement for enrollment in the study, Dr. Bekker pointed out, and pregnancy outcomes across the treatment arms were similar to the general population.
 

First in a Series of Trials

This is the first in a series of PURPOSE trials, Bekker reported. The phase 3 PURPOSE 2 trial, enrolling 3000 gay men, transgender women, transgender men and gender nonbinary people who have sex with male partners, is the second pivotal trial now underway.

Three other smaller trials are in the clinic in the United States and Europe.

PURPOSE 1 participants will continue to access lenacapavir until the product is available in South Africa and Uganda, Dr. Bekker said. Trial sponsor Gilead Sciences is also developing a direct licensing program to expedite generic access to the drug in high-incidence, resource-limited countries, she said.

Dr. Walensky and Dr. Baden report that lenacapavir currently costs about $43,000 annually in the United States. “But the results of the PURPOSE 1 trial have now created a moral imperative to make lenacapavir broadly accessible and affordable as PrEP” to people who were enrolled, as well as all those who are similarly eligible and could benefit.

So now we have a PrEP product with high efficacy, they added. “That is great news for science but not (yet) great for women.” 

Given the high pregnancy rate among participants in the PURPOSE 1 trial, Dr. Walensky and Dr. Baden point out the assessment of lenacapavir safety is a priority. They are also interested in learning more about drug resistance with this new option. 

“I f approved and delivered — rapidly, affordably, and equitably — to those who need or want it, this long-acting tool could help accelerate global progress in HIV prevention,” Dr. Lewin said.

Now, she added, “we eagerly await results from PURPOSE 2.”
 

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

TOPLINE:

More gastrointestinal and nervous symptom adverse events (AEs) are linked to apremilast than deucravacitinib, which is associated with more cutaneous AEs, according to a retrospective comparison using US Food and Drug Administration (FDA) data.

METHODOLOGY:

• To evaluate the adverse events associated with apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, and deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, data were drawn from the FDA’s Adverse Event Reporting System database.
• The Medex_UIMA_1.8.3 system was used to standardize drug names, and MedDRA terminology was used to encode, categorize, and localize signals.
• AE event signals were grouped by skin and subcutaneous tissue disorders, gastrointestinal disorders, infections and infestations, and nervous system disorders.

TAKEAWAY:

• There were 95,734 AE reports for apremilast and 760 AE reports for deucravacitinib, and AEs were found to be significant over time.
• The more common cutaneous AEs were psoriasis recurrence and acne (associated with apremilast) and skin burning and erythema (associated with deucravacitinib).
• The more common gastrointestinal AEs were diarrhea and nausea (apremilast) and mouth ulceration (deucravacitinib).
• Deucravacitinib-related pruritus and rash, as well as apremilast-related tension headache, were more common in women than men; deucravacitinib-related skin burning was more common in men.

IN PRACTICE:

The results “can help the doctors to choose the right treatment options based on the baseline characteristics of different patients,” said Yuanyuan Xu, a graduate student in the Department of Dermatology, Sichuan University, Chengdu, China.

SOURCE:

Mr. Xu presented the study as a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2024 annual meeting.

LIMITATIONS:

The study was retrospective and cannot prove causality, and there were far fewer AE reports related to deucravacitinib, likely because the drug was introduced more recently.

DISCLOSURES:

The study received no funding, and the authors had no relevant financial disclosures.

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

TOPLINE:

More gastrointestinal and nervous symptom adverse events (AEs) are linked to apremilast than deucravacitinib, which is associated with more cutaneous AEs, according to a retrospective comparison using US Food and Drug Administration (FDA) data.

METHODOLOGY:

• To evaluate the adverse events associated with apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, and deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, data were drawn from the FDA’s Adverse Event Reporting System database.
• The Medex_UIMA_1.8.3 system was used to standardize drug names, and MedDRA terminology was used to encode, categorize, and localize signals.
• AE event signals were grouped by skin and subcutaneous tissue disorders, gastrointestinal disorders, infections and infestations, and nervous system disorders.

TAKEAWAY:

• There were 95,734 AE reports for apremilast and 760 AE reports for deucravacitinib, and AEs were found to be significant over time.
• The more common cutaneous AEs were psoriasis recurrence and acne (associated with apremilast) and skin burning and erythema (associated with deucravacitinib).
• The more common gastrointestinal AEs were diarrhea and nausea (apremilast) and mouth ulceration (deucravacitinib).
• Deucravacitinib-related pruritus and rash, as well as apremilast-related tension headache, were more common in women than men; deucravacitinib-related skin burning was more common in men.

IN PRACTICE:

The results “can help the doctors to choose the right treatment options based on the baseline characteristics of different patients,” said Yuanyuan Xu, a graduate student in the Department of Dermatology, Sichuan University, Chengdu, China.

SOURCE:

Mr. Xu presented the study as a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2024 annual meeting.

LIMITATIONS:

The study was retrospective and cannot prove causality, and there were far fewer AE reports related to deucravacitinib, likely because the drug was introduced more recently.

DISCLOSURES:

The study received no funding, and the authors had no relevant financial disclosures.

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

TOPLINE:

More gastrointestinal and nervous symptom adverse events (AEs) are linked to apremilast than deucravacitinib, which is associated with more cutaneous AEs, according to a retrospective comparison using US Food and Drug Administration (FDA) data.

METHODOLOGY:

• To evaluate the adverse events associated with apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, and deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, data were drawn from the FDA’s Adverse Event Reporting System database.
• The Medex_UIMA_1.8.3 system was used to standardize drug names, and MedDRA terminology was used to encode, categorize, and localize signals.
• AE event signals were grouped by skin and subcutaneous tissue disorders, gastrointestinal disorders, infections and infestations, and nervous system disorders.

TAKEAWAY:

• There were 95,734 AE reports for apremilast and 760 AE reports for deucravacitinib, and AEs were found to be significant over time.
• The more common cutaneous AEs were psoriasis recurrence and acne (associated with apremilast) and skin burning and erythema (associated with deucravacitinib).
• The more common gastrointestinal AEs were diarrhea and nausea (apremilast) and mouth ulceration (deucravacitinib).
• Deucravacitinib-related pruritus and rash, as well as apremilast-related tension headache, were more common in women than men; deucravacitinib-related skin burning was more common in men.

IN PRACTICE:

The results “can help the doctors to choose the right treatment options based on the baseline characteristics of different patients,” said Yuanyuan Xu, a graduate student in the Department of Dermatology, Sichuan University, Chengdu, China.

SOURCE:

Mr. Xu presented the study as a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2024 annual meeting.

LIMITATIONS:

The study was retrospective and cannot prove causality, and there were far fewer AE reports related to deucravacitinib, likely because the drug was introduced more recently.

DISCLOSURES:

The study received no funding, and the authors had no relevant financial disclosures.

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

TOPLINE:

Rates of major adverse cardiovascular events (MACE) do not differ significantly among individual biologics used for psoriasis or psoriatic arthritis (PsA), a database analysis finds. 

METHODOLOGY:

• Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
• The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
• Subset analyses compared MACE in patients with and without existing cardiovascular disease.

TAKEAWAY:

• Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
• There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.

IN PRACTICE:

Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.

SOURCE:

Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. 

LIMITATIONS:

The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.

DISCLOSURES:

Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.

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

TOPLINE:

Rates of major adverse cardiovascular events (MACE) do not differ significantly among individual biologics used for psoriasis or psoriatic arthritis (PsA), a database analysis finds. 

METHODOLOGY:

• Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
• The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
• Subset analyses compared MACE in patients with and without existing cardiovascular disease.

TAKEAWAY:

• Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
• There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.

IN PRACTICE:

Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.

SOURCE:

Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. 

LIMITATIONS:

The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.

DISCLOSURES:

Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.

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

TOPLINE:

Rates of major adverse cardiovascular events (MACE) do not differ significantly among individual biologics used for psoriasis or psoriatic arthritis (PsA), a database analysis finds. 

METHODOLOGY:

• Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
• The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
• Subset analyses compared MACE in patients with and without existing cardiovascular disease.

TAKEAWAY:

• Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
• There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.

IN PRACTICE:

Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.

SOURCE:

Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. 

LIMITATIONS:

The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.

DISCLOSURES:

Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.

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

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

TORONTO — With rates of childhood obesity increasing to the point of becoming a public health concern, related skin conditions are also on the rise in the pediatric population, results of new research show.

The retrospective cohort study found markedly higher rates of skin infections, atopic dermatitis (AD), and acanthosis nigricans among children with overweight, compared with children with average weight.

“Many conditions associated with obesity are strong predictors of cardiovascular mortality as these children age, so doctors can play a key role in advocating for weight loss strategies in this population,” lead study author Samantha Epstein, third-year medical student at Case Western Reserve University, Cleveland, Ohio, said in an interview. The findings were presented at the annual meeting of the Society for Pediatric Dermatology.

Previous research has linked obesity, a chronic inflammatory condition, to psoriasis, AD, hidradenitis suppurativa (HS), acne vulgaris, infections, and rosacea in adults. However, there’s scant research exploring the connection between obesity and cutaneous conditions in children.

According to the Cleveland Clinic, childhood obesity is defined as a body mass index, which is weight in kg divided by the square of height in m², at or above the 95th percentile for age and sex in children aged 2 years or older.

For the study, Ms. Epstein and coauthor Sonal D. Shah, MD, associate professor, Department of Dermatology, Case Western Reserve University, and a board-certified pediatric dermatologist accessed a large national research database and used diagnostic codes to identify over 1 million children (mean age, 8.5 years). Most (about 44%) were White; about one-quarter were Black. The groups were propensity matched, so there were about equal numbers of youngsters with and without obesity and of boys and girls.

They collected data on AD, HS, rosacea, psoriasis, and acanthosis nigricans (a thickened purplish discoloration typically found in body folds around the armpits, groin, and neck). They also gathered information on comorbidities.

Acanthosis nigricans, which is linked to metabolic syndrome, type 2 diabetes, and insulin resistance , was more prevalent among children with obesity (20,885 cases in the with-obesity group and 336 in the without-obesity group, for a relative risk [RR] of 62.16 and an odds ratio [OR] of 64.38).

Skin and subcutaneous tissue infections were also more common among those with obesity (14,795 cases) vs 4720 cases among those without obesity (RR, 3.14; OR, 3.2). As for AD, there were 11,892 cases in the with-obesity group and 2983 in the without-obesity group (RR, 3.99; OR, 4.06). There were 1166 cases of psoriasis among those with obesity and 408 among those without obesity (RR, 2.86; OR, 2.88).

HS (587 cases in the with-obesity group and 70 in the without-obesity group; RR, 8.39; OR, 8.39) and rosacea (351 in the with-obesity group and 138 in the without-obesity group; RR, 2.54; OR, 2.55) were the least common skin conditions.

Higher Comorbidity Rates

Compared with their average-weight counterparts, the children with obesity had higher rates of comorbidities, including type 2 diabetes. Ms. Epstein noted that children with diabetes and obesity had increased risks for every skin condition except for infections of the skin and subcutaneous tissue when compared with children without obesity. 

Such infections were the most common skin conditions among children without obesity. “This was expected just due to the fact that children are outside, they’re playing in the grass and the dirt, and they get infected,” said Ms. Epstein. Still, these infections were three times more common in youngsters with obesity.

Although acanthosis nigricans is “highly correlated” with type 2 diabetes, “not as many children as we would expect in this population have developed type 2 diabetes,” said Ms. Epstein. This might make some sense, though, because these children are still quite young. “When dermatologists recognize this skin condition, they can advocate for weight loss management to try to prevent it.”

Other conditions seen more often in the overweight children with overweight included: hypertension, hyperlipidemia, obstructive sleep apnea, polycystic ovarian syndrome, attention-deficit/hyperactivity disorder, major depressive disorder, depressive episodes, and anxiety (all P < .001).

Commenting on the results, Sonia Havele, MD, a pediatrician and dermatology resident at Children’s Mercy Hospital, Kansas City, Missouri, said in an interview that the study reflects trends that she and her colleagues see in clinic: There are more common skin conditions in their patients with obesity.

She agreed that it offers an opening for education. “The results of this study highlight the opportunity we have as pediatric dermatologists to provide additional counseling on obesity and offer referrals to our colleagues in endocrinology, gastroenterology, and nutrition if needed.”

No conflicts of interest were reported.

TORONTO — With rates of childhood obesity increasing to the point of becoming a public health concern, related skin conditions are also on the rise in the pediatric population, results of new research show.

The retrospective cohort study found markedly higher rates of skin infections, atopic dermatitis (AD), and acanthosis nigricans among children with overweight, compared with children with average weight.

“Many conditions associated with obesity are strong predictors of cardiovascular mortality as these children age, so doctors can play a key role in advocating for weight loss strategies in this population,” lead study author Samantha Epstein, third-year medical student at Case Western Reserve University, Cleveland, Ohio, said in an interview. The findings were presented at the annual meeting of the Society for Pediatric Dermatology.

Previous research has linked obesity, a chronic inflammatory condition, to psoriasis, AD, hidradenitis suppurativa (HS), acne vulgaris, infections, and rosacea in adults. However, there’s scant research exploring the connection between obesity and cutaneous conditions in children.

According to the Cleveland Clinic, childhood obesity is defined as a body mass index, which is weight in kg divided by the square of height in m², at or above the 95th percentile for age and sex in children aged 2 years or older.

For the study, Ms. Epstein and coauthor Sonal D. Shah, MD, associate professor, Department of Dermatology, Case Western Reserve University, and a board-certified pediatric dermatologist accessed a large national research database and used diagnostic codes to identify over 1 million children (mean age, 8.5 years). Most (about 44%) were White; about one-quarter were Black. The groups were propensity matched, so there were about equal numbers of youngsters with and without obesity and of boys and girls.

They collected data on AD, HS, rosacea, psoriasis, and acanthosis nigricans (a thickened purplish discoloration typically found in body folds around the armpits, groin, and neck). They also gathered information on comorbidities.

Acanthosis nigricans, which is linked to metabolic syndrome, type 2 diabetes, and insulin resistance , was more prevalent among children with obesity (20,885 cases in the with-obesity group and 336 in the without-obesity group, for a relative risk [RR] of 62.16 and an odds ratio [OR] of 64.38).

Skin and subcutaneous tissue infections were also more common among those with obesity (14,795 cases) vs 4720 cases among those without obesity (RR, 3.14; OR, 3.2). As for AD, there were 11,892 cases in the with-obesity group and 2983 in the without-obesity group (RR, 3.99; OR, 4.06). There were 1166 cases of psoriasis among those with obesity and 408 among those without obesity (RR, 2.86; OR, 2.88).

HS (587 cases in the with-obesity group and 70 in the without-obesity group; RR, 8.39; OR, 8.39) and rosacea (351 in the with-obesity group and 138 in the without-obesity group; RR, 2.54; OR, 2.55) were the least common skin conditions.

Higher Comorbidity Rates

Compared with their average-weight counterparts, the children with obesity had higher rates of comorbidities, including type 2 diabetes. Ms. Epstein noted that children with diabetes and obesity had increased risks for every skin condition except for infections of the skin and subcutaneous tissue when compared with children without obesity. 

Such infections were the most common skin conditions among children without obesity. “This was expected just due to the fact that children are outside, they’re playing in the grass and the dirt, and they get infected,” said Ms. Epstein. Still, these infections were three times more common in youngsters with obesity.

Although acanthosis nigricans is “highly correlated” with type 2 diabetes, “not as many children as we would expect in this population have developed type 2 diabetes,” said Ms. Epstein. This might make some sense, though, because these children are still quite young. “When dermatologists recognize this skin condition, they can advocate for weight loss management to try to prevent it.”

Other conditions seen more often in the overweight children with overweight included: hypertension, hyperlipidemia, obstructive sleep apnea, polycystic ovarian syndrome, attention-deficit/hyperactivity disorder, major depressive disorder, depressive episodes, and anxiety (all P < .001).

Commenting on the results, Sonia Havele, MD, a pediatrician and dermatology resident at Children’s Mercy Hospital, Kansas City, Missouri, said in an interview that the study reflects trends that she and her colleagues see in clinic: There are more common skin conditions in their patients with obesity.

She agreed that it offers an opening for education. “The results of this study highlight the opportunity we have as pediatric dermatologists to provide additional counseling on obesity and offer referrals to our colleagues in endocrinology, gastroenterology, and nutrition if needed.”

No conflicts of interest were reported.

TORONTO — With rates of childhood obesity increasing to the point of becoming a public health concern, related skin conditions are also on the rise in the pediatric population, results of new research show.

The retrospective cohort study found markedly higher rates of skin infections, atopic dermatitis (AD), and acanthosis nigricans among children with overweight, compared with children with average weight.

“Many conditions associated with obesity are strong predictors of cardiovascular mortality as these children age, so doctors can play a key role in advocating for weight loss strategies in this population,” lead study author Samantha Epstein, third-year medical student at Case Western Reserve University, Cleveland, Ohio, said in an interview. The findings were presented at the annual meeting of the Society for Pediatric Dermatology.

Previous research has linked obesity, a chronic inflammatory condition, to psoriasis, AD, hidradenitis suppurativa (HS), acne vulgaris, infections, and rosacea in adults. However, there’s scant research exploring the connection between obesity and cutaneous conditions in children.

According to the Cleveland Clinic, childhood obesity is defined as a body mass index, which is weight in kg divided by the square of height in m², at or above the 95th percentile for age and sex in children aged 2 years or older.

For the study, Ms. Epstein and coauthor Sonal D. Shah, MD, associate professor, Department of Dermatology, Case Western Reserve University, and a board-certified pediatric dermatologist accessed a large national research database and used diagnostic codes to identify over 1 million children (mean age, 8.5 years). Most (about 44%) were White; about one-quarter were Black. The groups were propensity matched, so there were about equal numbers of youngsters with and without obesity and of boys and girls.

They collected data on AD, HS, rosacea, psoriasis, and acanthosis nigricans (a thickened purplish discoloration typically found in body folds around the armpits, groin, and neck). They also gathered information on comorbidities.

Acanthosis nigricans, which is linked to metabolic syndrome, type 2 diabetes, and insulin resistance , was more prevalent among children with obesity (20,885 cases in the with-obesity group and 336 in the without-obesity group, for a relative risk [RR] of 62.16 and an odds ratio [OR] of 64.38).

Skin and subcutaneous tissue infections were also more common among those with obesity (14,795 cases) vs 4720 cases among those without obesity (RR, 3.14; OR, 3.2). As for AD, there were 11,892 cases in the with-obesity group and 2983 in the without-obesity group (RR, 3.99; OR, 4.06). There were 1166 cases of psoriasis among those with obesity and 408 among those without obesity (RR, 2.86; OR, 2.88).

HS (587 cases in the with-obesity group and 70 in the without-obesity group; RR, 8.39; OR, 8.39) and rosacea (351 in the with-obesity group and 138 in the without-obesity group; RR, 2.54; OR, 2.55) were the least common skin conditions.

Higher Comorbidity Rates

Compared with their average-weight counterparts, the children with obesity had higher rates of comorbidities, including type 2 diabetes. Ms. Epstein noted that children with diabetes and obesity had increased risks for every skin condition except for infections of the skin and subcutaneous tissue when compared with children without obesity. 

Such infections were the most common skin conditions among children without obesity. “This was expected just due to the fact that children are outside, they’re playing in the grass and the dirt, and they get infected,” said Ms. Epstein. Still, these infections were three times more common in youngsters with obesity.

Although acanthosis nigricans is “highly correlated” with type 2 diabetes, “not as many children as we would expect in this population have developed type 2 diabetes,” said Ms. Epstein. This might make some sense, though, because these children are still quite young. “When dermatologists recognize this skin condition, they can advocate for weight loss management to try to prevent it.”

Other conditions seen more often in the overweight children with overweight included: hypertension, hyperlipidemia, obstructive sleep apnea, polycystic ovarian syndrome, attention-deficit/hyperactivity disorder, major depressive disorder, depressive episodes, and anxiety (all P < .001).

Commenting on the results, Sonia Havele, MD, a pediatrician and dermatology resident at Children’s Mercy Hospital, Kansas City, Missouri, said in an interview that the study reflects trends that she and her colleagues see in clinic: There are more common skin conditions in their patients with obesity.

She agreed that it offers an opening for education. “The results of this study highlight the opportunity we have as pediatric dermatologists to provide additional counseling on obesity and offer referrals to our colleagues in endocrinology, gastroenterology, and nutrition if needed.”

No conflicts of interest were reported.

Adolescents with nonsegmental vitiligo who applied topical ruxolitinib, 1.5% cream were more likely than adults to achieve complete repigmentation, a post hoc analysis of pivotal clinical trial data showed. 

“We consider repigmenting vitiligo a two-step process, where the overactive immune system needs to be calmed down and then the melanocytes need to repopulate to the white areas,” one of the study investigators, David Rosmarin, MD, chair of the Department of Dermatology at Indiana University School of Medicine, Indianapolis, said in an interview in advance of the annual meeting of the Society for Pediatric Dermatology, where the study results were presented during a poster session. “In younger patients, it may be that the melanocytes are more rapidly repigmenting the patches, which is why we see this effect.”

Ruxolitinib, 1.5% cream (Opzelura) is a Janus kinase inhibitor approved for the treatment of nonsegmental vitiligo in patients 12 years of age and older. Dr. Rosmarin and colleagues sought to evaluate differences in rates of complete or near-complete repigmentation and repigmentation by body region between adolescents 12-17 years of age and adults 18 years of age and older who applied ruxolitinib cream twice daily. The researchers evaluated patients who were initially randomized to ruxolitinib cream, 1.5% in the pivotal TRuE-V1 and TRuE-V2 studies and applied it for up to 104 weeks. Complete facial improvement was defined as 100% improvement on the Facial Vitiligo Area Scoring Index (F-VASI 100) from baseline, and near-total improvement was categorized as a ≥ 75% or ≥ 90% improvement from baseline on the Total body VASI (T-VASI). Responses for each of six body regions, excluding the face, were assessed by the proportion of patients who achieved at least a 50% improvement from baseline on the T-VASI.

Compared with adults, a greater proportion of adolescents achieved F-VASI 100 at week 24 (5.7% [3/53] vs 2.9% [10/341], respectively), but there were no differences between the two groups at week 52 (8.0% [4/50] vs 8.0% [24/300]). Response rates were greater among adolescents vs adults for T-VASI 75 at weeks 24 (13.2% [7/53] vs 5.6% [19/341]) and 52 (22.0% [11/50] vs 20.3% [61/300]), as well as T-VASI 90 at weeks 24 (3.8% [2/53] vs 0.3% [1/341]) and 52 (12.0% [6/50] vs 4.0% [12/300]).

The researchers observed that VASI 50 responses by body region were generally similar between adolescents and adults, but a greater proportion of adolescents achieved a VASI 50 in lower extremities (67.3% [33/49] vs 51.8% [118/228]) and feet (37.5% [12/32] vs 27.9% [51/183]) at week 52.

FG Trade/Getty Images

“Adolescents repigmented more rapidly than adults, so that at 24 weeks, more teens had complete facial repigmentation and T-VASI 75 and T-VASI 90 results,” Dr. Rosmarin said. “With continued use of ruxolitinib cream, both more adults and adolescents achieved greater repigmentation.” He acknowledged certain limitations of the study, including the fact that it was only vehicle controlled up through 24 weeks and that, after week 52, there were fewer patients who completed the long-term extension.

“The take-home message is that ruxolitinib cream can effectively and safely help many patients repigment, including adolescents,” he said.

The study was funded by topical ruxolitinib manufacturer Incyte. Dr. Rosmarin disclosed that he has consulted, spoken for, or conducted trials for AbbVie, Abcuro, Almirall, AltruBio, Amgen, Arena, Astria, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant Sciences, Dermira, Galderma, Incyte, Janssen, Kyowa Kirin, Lilly, Merck, Nektar, Novartis, Pfizer, RAPT, Regeneron, Recludix Pharma, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, Viela Bio, and Zura.

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

Adolescents with nonsegmental vitiligo who applied topical ruxolitinib, 1.5% cream were more likely than adults to achieve complete repigmentation, a post hoc analysis of pivotal clinical trial data showed. 

“We consider repigmenting vitiligo a two-step process, where the overactive immune system needs to be calmed down and then the melanocytes need to repopulate to the white areas,” one of the study investigators, David Rosmarin, MD, chair of the Department of Dermatology at Indiana University School of Medicine, Indianapolis, said in an interview in advance of the annual meeting of the Society for Pediatric Dermatology, where the study results were presented during a poster session. “In younger patients, it may be that the melanocytes are more rapidly repigmenting the patches, which is why we see this effect.”

Ruxolitinib, 1.5% cream (Opzelura) is a Janus kinase inhibitor approved for the treatment of nonsegmental vitiligo in patients 12 years of age and older. Dr. Rosmarin and colleagues sought to evaluate differences in rates of complete or near-complete repigmentation and repigmentation by body region between adolescents 12-17 years of age and adults 18 years of age and older who applied ruxolitinib cream twice daily. The researchers evaluated patients who were initially randomized to ruxolitinib cream, 1.5% in the pivotal TRuE-V1 and TRuE-V2 studies and applied it for up to 104 weeks. Complete facial improvement was defined as 100% improvement on the Facial Vitiligo Area Scoring Index (F-VASI 100) from baseline, and near-total improvement was categorized as a ≥ 75% or ≥ 90% improvement from baseline on the Total body VASI (T-VASI). Responses for each of six body regions, excluding the face, were assessed by the proportion of patients who achieved at least a 50% improvement from baseline on the T-VASI.

Compared with adults, a greater proportion of adolescents achieved F-VASI 100 at week 24 (5.7% [3/53] vs 2.9% [10/341], respectively), but there were no differences between the two groups at week 52 (8.0% [4/50] vs 8.0% [24/300]). Response rates were greater among adolescents vs adults for T-VASI 75 at weeks 24 (13.2% [7/53] vs 5.6% [19/341]) and 52 (22.0% [11/50] vs 20.3% [61/300]), as well as T-VASI 90 at weeks 24 (3.8% [2/53] vs 0.3% [1/341]) and 52 (12.0% [6/50] vs 4.0% [12/300]).

The researchers observed that VASI 50 responses by body region were generally similar between adolescents and adults, but a greater proportion of adolescents achieved a VASI 50 in lower extremities (67.3% [33/49] vs 51.8% [118/228]) and feet (37.5% [12/32] vs 27.9% [51/183]) at week 52.

FG Trade/Getty Images

“Adolescents repigmented more rapidly than adults, so that at 24 weeks, more teens had complete facial repigmentation and T-VASI 75 and T-VASI 90 results,” Dr. Rosmarin said. “With continued use of ruxolitinib cream, both more adults and adolescents achieved greater repigmentation.” He acknowledged certain limitations of the study, including the fact that it was only vehicle controlled up through 24 weeks and that, after week 52, there were fewer patients who completed the long-term extension.

“The take-home message is that ruxolitinib cream can effectively and safely help many patients repigment, including adolescents,” he said.

The study was funded by topical ruxolitinib manufacturer Incyte. Dr. Rosmarin disclosed that he has consulted, spoken for, or conducted trials for AbbVie, Abcuro, Almirall, AltruBio, Amgen, Arena, Astria, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant Sciences, Dermira, Galderma, Incyte, Janssen, Kyowa Kirin, Lilly, Merck, Nektar, Novartis, Pfizer, RAPT, Regeneron, Recludix Pharma, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, Viela Bio, and Zura.

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

Adolescents with nonsegmental vitiligo who applied topical ruxolitinib, 1.5% cream were more likely than adults to achieve complete repigmentation, a post hoc analysis of pivotal clinical trial data showed. 

“We consider repigmenting vitiligo a two-step process, where the overactive immune system needs to be calmed down and then the melanocytes need to repopulate to the white areas,” one of the study investigators, David Rosmarin, MD, chair of the Department of Dermatology at Indiana University School of Medicine, Indianapolis, said in an interview in advance of the annual meeting of the Society for Pediatric Dermatology, where the study results were presented during a poster session. “In younger patients, it may be that the melanocytes are more rapidly repigmenting the patches, which is why we see this effect.”

Ruxolitinib, 1.5% cream (Opzelura) is a Janus kinase inhibitor approved for the treatment of nonsegmental vitiligo in patients 12 years of age and older. Dr. Rosmarin and colleagues sought to evaluate differences in rates of complete or near-complete repigmentation and repigmentation by body region between adolescents 12-17 years of age and adults 18 years of age and older who applied ruxolitinib cream twice daily. The researchers evaluated patients who were initially randomized to ruxolitinib cream, 1.5% in the pivotal TRuE-V1 and TRuE-V2 studies and applied it for up to 104 weeks. Complete facial improvement was defined as 100% improvement on the Facial Vitiligo Area Scoring Index (F-VASI 100) from baseline, and near-total improvement was categorized as a ≥ 75% or ≥ 90% improvement from baseline on the Total body VASI (T-VASI). Responses for each of six body regions, excluding the face, were assessed by the proportion of patients who achieved at least a 50% improvement from baseline on the T-VASI.

Compared with adults, a greater proportion of adolescents achieved F-VASI 100 at week 24 (5.7% [3/53] vs 2.9% [10/341], respectively), but there were no differences between the two groups at week 52 (8.0% [4/50] vs 8.0% [24/300]). Response rates were greater among adolescents vs adults for T-VASI 75 at weeks 24 (13.2% [7/53] vs 5.6% [19/341]) and 52 (22.0% [11/50] vs 20.3% [61/300]), as well as T-VASI 90 at weeks 24 (3.8% [2/53] vs 0.3% [1/341]) and 52 (12.0% [6/50] vs 4.0% [12/300]).

The researchers observed that VASI 50 responses by body region were generally similar between adolescents and adults, but a greater proportion of adolescents achieved a VASI 50 in lower extremities (67.3% [33/49] vs 51.8% [118/228]) and feet (37.5% [12/32] vs 27.9% [51/183]) at week 52.

FG Trade/Getty Images

“Adolescents repigmented more rapidly than adults, so that at 24 weeks, more teens had complete facial repigmentation and T-VASI 75 and T-VASI 90 results,” Dr. Rosmarin said. “With continued use of ruxolitinib cream, both more adults and adolescents achieved greater repigmentation.” He acknowledged certain limitations of the study, including the fact that it was only vehicle controlled up through 24 weeks and that, after week 52, there were fewer patients who completed the long-term extension.

“The take-home message is that ruxolitinib cream can effectively and safely help many patients repigment, including adolescents,” he said.

The study was funded by topical ruxolitinib manufacturer Incyte. Dr. Rosmarin disclosed that he has consulted, spoken for, or conducted trials for AbbVie, Abcuro, Almirall, AltruBio, Amgen, Arena, Astria, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant Sciences, Dermira, Galderma, Incyte, Janssen, Kyowa Kirin, Lilly, Merck, Nektar, Novartis, Pfizer, RAPT, Regeneron, Recludix Pharma, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, Viela Bio, and Zura.

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

SEATTLE — Tissue resident memory (TRM) T cells are a hot topic lately in the treatment of psoriasis. These cells reside in the skin and other tissues and promote the inflammatory response, likely contributing to psoriasis symptoms. In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.

This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.

Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.

TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.

Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”

She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”

Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”

There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood. 

Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”

During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.

Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.

Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”

Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said. 

Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB. 

SEATTLE — Tissue resident memory (TRM) T cells are a hot topic lately in the treatment of psoriasis. These cells reside in the skin and other tissues and promote the inflammatory response, likely contributing to psoriasis symptoms. In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.

This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.

Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.

TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.

Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”

She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”

Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”

There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood. 

Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”

During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.

Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.

Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”

Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said. 

Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB. 

SEATTLE — Tissue resident memory (TRM) T cells are a hot topic lately in the treatment of psoriasis. These cells reside in the skin and other tissues and promote the inflammatory response, likely contributing to psoriasis symptoms. In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.

This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.

Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.

TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.

Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”

She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”

Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”

There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood. 

Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”

During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.

Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.

Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”

Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said. 

Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB. 

WASHINGTON — A risk-stratified upper age limit may be beneficial for colorectal cancer (CRC) screening among patients who are ages 75 and older, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, interval CRC risk can vary substantially based on the fecal hemoglobin (f-Hb) concentration in the patient’s last fecal immunochemical test (FIT), as well as the number of prior screening rounds.

“Less is known about what happens after the upper age limit has been reached and individuals are not invited to participate in more screening rounds. This is important as life expectancy is increasing, and it is increasingly important to consider the most efficient way of screening the elderly,” said lead author Brenda van Stigt, a PhD candidate focused on cancer screening at Erasmus University Medical Center in Rotterdam, the Netherlands.

In the Netherlands, adults between ages 55 and 75 are invited to participate in stool-based CRC screening every 2 years. Based on a fecal immunochemical testing (FIT) threshold of 47 μg Hb/g, those who test positive are referred to colonoscopy, and those who test negative are invited to participate again after a 2-year period.

FIT can play a major role in risk stratification, Ms. van Stigt noted, along with other factors that influence CRC risk, such as age, sex, and CRC screening history. Although this is documented for ages 55-75, she and colleagues wanted to know more about what happens after age 75.

Ms. Van Stigt and colleagues conducted a population-based study by analyzing Dutch national cancer registry data and FIT results around the final screening at age 75, looking at those who were diagnosed with CRC within 24 months of their last negative FIT. The researchers assessed interval CRC risk and cancer stage, accounting for sex, last f-Hb concentration, and the number of screening rounds.

Among 305,761 people with a complete 24-month follow-up after a negative FIT, 661 patients were diagnosed with interval CRC, indicating an overall interval CRC risk of 21.6 per 10,000 individuals with a negative FIT. There were no significant differences by sex.

However, there were differences by screening rounds, with those who had participated in three or four screening rounds having a lower risk than those who participated only once (HR, .49).

In addition, those with detectable f-Hb (>0 μg Hb/g) in their last screening round had a much higher interval CRC risk (HR, 4.87), at 65.8 per 10,000 negative FITs, compared with 13.8 per 10,000 among those without detectable f-Hb. Interval CRC risk also increased over time for those with detectable f-Hb.

About 15% of the total population had detectable f-Hb, whereas 46% of those with interval CRC had detectable f-Hb, Ms. van Stigt said, meaning that nearly half of patients who were diagnosed with interval CRC already had detectable f-Hb in their prior FIT.

In a survival analysis, there was no association between interval CRC risk and sex. However, those who participated in three or four screening rounds were half as likely to be diagnosed than those who participated once or twice, and those with detectable f-Hb were five times as likely to be diagnosed.

For late-stage CRC, there was no association with sex or the number of screening rounds. Detectable f-Hb was associated with not only a higher risk of interval CRC but also a late-stage diagnosis.

“These findings indicate that one uniform age to stop screening is suboptimal,” Ms. van Stigt said. “Personalized screening strategies should, therefore, also ideally incorporate a risk-stratified age to stop screening.”

The US Preventive Services Task Force recommends that clinicians personalize screening for ages 76-85, accounting for overall health, prior screening history, and patient preferences.

“But we have no clear guidance on how to quantify or weigh these factors. This interesting study highlights how one of these factors (prior screening history) and fecal hemoglobin level (an emerging factor) are powerful stratifiers of subsequent colorectal cancer risk,” said Sameer D. Saini, MD, AGAF, director and research investigator at the VA Ann Arbor Healthcare System’s Center for Clinical Management Research. Dr. Saini wasn’t involved with the study.

At the clinical level, Dr. Saini said, sophisticated modeling is needed to understand the interaction with competing risks and identify the optimal screening strategies for patients at varying levels of cancer risk and life expectancy. Models could also help to quantify the population benefits and cost-effectiveness of personalized screening.

“Finally, it is important to note that, in many health systems, access to quantitative FIT may be limited,” he said. “These data may be less informative if colonoscopy is the primary mode of screening.”

Ms. van Stigt and Dr. Saini reported no relevant disclosures.

WASHINGTON — A risk-stratified upper age limit may be beneficial for colorectal cancer (CRC) screening among patients who are ages 75 and older, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, interval CRC risk can vary substantially based on the fecal hemoglobin (f-Hb) concentration in the patient’s last fecal immunochemical test (FIT), as well as the number of prior screening rounds.

“Less is known about what happens after the upper age limit has been reached and individuals are not invited to participate in more screening rounds. This is important as life expectancy is increasing, and it is increasingly important to consider the most efficient way of screening the elderly,” said lead author Brenda van Stigt, a PhD candidate focused on cancer screening at Erasmus University Medical Center in Rotterdam, the Netherlands.

In the Netherlands, adults between ages 55 and 75 are invited to participate in stool-based CRC screening every 2 years. Based on a fecal immunochemical testing (FIT) threshold of 47 μg Hb/g, those who test positive are referred to colonoscopy, and those who test negative are invited to participate again after a 2-year period.

FIT can play a major role in risk stratification, Ms. van Stigt noted, along with other factors that influence CRC risk, such as age, sex, and CRC screening history. Although this is documented for ages 55-75, she and colleagues wanted to know more about what happens after age 75.

Ms. Van Stigt and colleagues conducted a population-based study by analyzing Dutch national cancer registry data and FIT results around the final screening at age 75, looking at those who were diagnosed with CRC within 24 months of their last negative FIT. The researchers assessed interval CRC risk and cancer stage, accounting for sex, last f-Hb concentration, and the number of screening rounds.

Among 305,761 people with a complete 24-month follow-up after a negative FIT, 661 patients were diagnosed with interval CRC, indicating an overall interval CRC risk of 21.6 per 10,000 individuals with a negative FIT. There were no significant differences by sex.

However, there were differences by screening rounds, with those who had participated in three or four screening rounds having a lower risk than those who participated only once (HR, .49).

In addition, those with detectable f-Hb (>0 μg Hb/g) in their last screening round had a much higher interval CRC risk (HR, 4.87), at 65.8 per 10,000 negative FITs, compared with 13.8 per 10,000 among those without detectable f-Hb. Interval CRC risk also increased over time for those with detectable f-Hb.

About 15% of the total population had detectable f-Hb, whereas 46% of those with interval CRC had detectable f-Hb, Ms. van Stigt said, meaning that nearly half of patients who were diagnosed with interval CRC already had detectable f-Hb in their prior FIT.

In a survival analysis, there was no association between interval CRC risk and sex. However, those who participated in three or four screening rounds were half as likely to be diagnosed than those who participated once or twice, and those with detectable f-Hb were five times as likely to be diagnosed.

For late-stage CRC, there was no association with sex or the number of screening rounds. Detectable f-Hb was associated with not only a higher risk of interval CRC but also a late-stage diagnosis.

“These findings indicate that one uniform age to stop screening is suboptimal,” Ms. van Stigt said. “Personalized screening strategies should, therefore, also ideally incorporate a risk-stratified age to stop screening.”

The US Preventive Services Task Force recommends that clinicians personalize screening for ages 76-85, accounting for overall health, prior screening history, and patient preferences.

“But we have no clear guidance on how to quantify or weigh these factors. This interesting study highlights how one of these factors (prior screening history) and fecal hemoglobin level (an emerging factor) are powerful stratifiers of subsequent colorectal cancer risk,” said Sameer D. Saini, MD, AGAF, director and research investigator at the VA Ann Arbor Healthcare System’s Center for Clinical Management Research. Dr. Saini wasn’t involved with the study.

At the clinical level, Dr. Saini said, sophisticated modeling is needed to understand the interaction with competing risks and identify the optimal screening strategies for patients at varying levels of cancer risk and life expectancy. Models could also help to quantify the population benefits and cost-effectiveness of personalized screening.

“Finally, it is important to note that, in many health systems, access to quantitative FIT may be limited,” he said. “These data may be less informative if colonoscopy is the primary mode of screening.”

Ms. van Stigt and Dr. Saini reported no relevant disclosures.

WASHINGTON — A risk-stratified upper age limit may be beneficial for colorectal cancer (CRC) screening among patients who are ages 75 and older, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, interval CRC risk can vary substantially based on the fecal hemoglobin (f-Hb) concentration in the patient’s last fecal immunochemical test (FIT), as well as the number of prior screening rounds.

“Less is known about what happens after the upper age limit has been reached and individuals are not invited to participate in more screening rounds. This is important as life expectancy is increasing, and it is increasingly important to consider the most efficient way of screening the elderly,” said lead author Brenda van Stigt, a PhD candidate focused on cancer screening at Erasmus University Medical Center in Rotterdam, the Netherlands.

In the Netherlands, adults between ages 55 and 75 are invited to participate in stool-based CRC screening every 2 years. Based on a fecal immunochemical testing (FIT) threshold of 47 μg Hb/g, those who test positive are referred to colonoscopy, and those who test negative are invited to participate again after a 2-year period.

FIT can play a major role in risk stratification, Ms. van Stigt noted, along with other factors that influence CRC risk, such as age, sex, and CRC screening history. Although this is documented for ages 55-75, she and colleagues wanted to know more about what happens after age 75.

Ms. Van Stigt and colleagues conducted a population-based study by analyzing Dutch national cancer registry data and FIT results around the final screening at age 75, looking at those who were diagnosed with CRC within 24 months of their last negative FIT. The researchers assessed interval CRC risk and cancer stage, accounting for sex, last f-Hb concentration, and the number of screening rounds.

Among 305,761 people with a complete 24-month follow-up after a negative FIT, 661 patients were diagnosed with interval CRC, indicating an overall interval CRC risk of 21.6 per 10,000 individuals with a negative FIT. There were no significant differences by sex.

However, there were differences by screening rounds, with those who had participated in three or four screening rounds having a lower risk than those who participated only once (HR, .49).

In addition, those with detectable f-Hb (>0 μg Hb/g) in their last screening round had a much higher interval CRC risk (HR, 4.87), at 65.8 per 10,000 negative FITs, compared with 13.8 per 10,000 among those without detectable f-Hb. Interval CRC risk also increased over time for those with detectable f-Hb.

About 15% of the total population had detectable f-Hb, whereas 46% of those with interval CRC had detectable f-Hb, Ms. van Stigt said, meaning that nearly half of patients who were diagnosed with interval CRC already had detectable f-Hb in their prior FIT.

In a survival analysis, there was no association between interval CRC risk and sex. However, those who participated in three or four screening rounds were half as likely to be diagnosed than those who participated once or twice, and those with detectable f-Hb were five times as likely to be diagnosed.

For late-stage CRC, there was no association with sex or the number of screening rounds. Detectable f-Hb was associated with not only a higher risk of interval CRC but also a late-stage diagnosis.

“These findings indicate that one uniform age to stop screening is suboptimal,” Ms. van Stigt said. “Personalized screening strategies should, therefore, also ideally incorporate a risk-stratified age to stop screening.”

The US Preventive Services Task Force recommends that clinicians personalize screening for ages 76-85, accounting for overall health, prior screening history, and patient preferences.

“But we have no clear guidance on how to quantify or weigh these factors. This interesting study highlights how one of these factors (prior screening history) and fecal hemoglobin level (an emerging factor) are powerful stratifiers of subsequent colorectal cancer risk,” said Sameer D. Saini, MD, AGAF, director and research investigator at the VA Ann Arbor Healthcare System’s Center for Clinical Management Research. Dr. Saini wasn’t involved with the study.

At the clinical level, Dr. Saini said, sophisticated modeling is needed to understand the interaction with competing risks and identify the optimal screening strategies for patients at varying levels of cancer risk and life expectancy. Models could also help to quantify the population benefits and cost-effectiveness of personalized screening.

“Finally, it is important to note that, in many health systems, access to quantitative FIT may be limited,” he said. “These data may be less informative if colonoscopy is the primary mode of screening.”

Ms. van Stigt and Dr. Saini reported no relevant disclosures.