Doug Brunk

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Dr. Chovatiya

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Dr. Chovatiya

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Dr. Chovatiya

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

A significant number of patients with moderate-to-severe atopic dermatitis (AD) failed to achieve adequate disease control with systemic therapies over 12 months in a study of patient registry data, indicating a substantial degree of “therapeutic inertia,” the study’s lead author, Jonathan I. Silverberg, MD, PhD, MPH, reported.

The findings come from an analysis of real-world outcomes from the TARGET-DERM AD registry, which Dr. Silverberg, professor and director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. He characterized the findings as “patients just getting stuck with a therapy and not advancing when they need to.”

TARGET-DERM AD is a longitudinal observational study of people with AD at 39 academic centers in the United States and Canada. Dr. Silverberg and his coinvestigators evaluated the proportion of patients who were experiencing an inadequate response after receiving systemic therapy and continuing on the same treatment for 3-12 months. “These are patients who are receiving their first or advanced systemic therapy, and the question is, how long did they stay on it, even if they’re not doing so well?” Dr. Silverberg said.

The researchers identified and compared the proportions of patients not achieving moderate or optimal clinician-reported outcome targets on patients with AD treated with their first systemic therapy. Advanced systemic therapy (AST) included abrocitinib, dupilumab, tralokinumab, or upadacitinib, while conventional systemic therapy (CST) included methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, and systemic corticosteroids.

Patients in TARGET-DERM AD were treated and maintained on their first systemic therapy (either advanced or conventional) for up to 12 months. They had a validated Investigator’s Global Assessment of AD (vIGA-AD) score of 3 or 4 less than 45 days prior to initiation of systemic therapy or up to 14 days afterward. They also had at least one vIGA-AD assessment 3-12 months after initiating treatment. Outcome measures included IGA (defined as a score of 2 or less, with an optional target of 0 or 1), BSA (defined as a 50% BSA improvement, with an optimal target BSA of 2% or less), and the Worst-Itch Numeric Rating Scale (defined as at least a 4-point reduction, with an optimal target of 1 or less).

The analysis included 445 patients with a mean age of 31 years at enrollment. More than half (62%) were female and 45% were non-Hispanic Whites. Most patients (92%) were on an AST, mainly dupilumab, with smaller proportions treated with either tralokinumab, upadacitinib, or abrocitinib. Fewer than 10% of patients in the registry were being treated with CSTs.

At 6 months, 37% and approximately 67% of the AST-treated patients had inadequate responses in terms of skin clearance and itch outcomes, respectively. At 12 months, these figures were about 30% and 66%, respectively. CST-treated patients showed a similar trend. For patients starting an AST on or after Sept. 21, 2021, when three additional AST options were available (tralokinumab, upadacitinib, and abrocitinib), the proportion of patients demonstrating an adequate response over 12 months was generally similar to the overall cohort of those on ASTs.

“These findings suggest a need for alternative therapies and management strategies in AD treatment,” concluded Dr. Silverberg, who chaired the RAD symposium.

Dr. Silverberg reported being a consultant and/or an adviser for many pharmaceutical companies, and has received grant or research support from Galderma and Pfizer. The TARGET-DERM study is sponsored by Target PharmaSolutions.

A significant number of patients with moderate-to-severe atopic dermatitis (AD) failed to achieve adequate disease control with systemic therapies over 12 months in a study of patient registry data, indicating a substantial degree of “therapeutic inertia,” the study’s lead author, Jonathan I. Silverberg, MD, PhD, MPH, reported.

The findings come from an analysis of real-world outcomes from the TARGET-DERM AD registry, which Dr. Silverberg, professor and director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. He characterized the findings as “patients just getting stuck with a therapy and not advancing when they need to.”

TARGET-DERM AD is a longitudinal observational study of people with AD at 39 academic centers in the United States and Canada. Dr. Silverberg and his coinvestigators evaluated the proportion of patients who were experiencing an inadequate response after receiving systemic therapy and continuing on the same treatment for 3-12 months. “These are patients who are receiving their first or advanced systemic therapy, and the question is, how long did they stay on it, even if they’re not doing so well?” Dr. Silverberg said.

The researchers identified and compared the proportions of patients not achieving moderate or optimal clinician-reported outcome targets on patients with AD treated with their first systemic therapy. Advanced systemic therapy (AST) included abrocitinib, dupilumab, tralokinumab, or upadacitinib, while conventional systemic therapy (CST) included methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, and systemic corticosteroids.

Patients in TARGET-DERM AD were treated and maintained on their first systemic therapy (either advanced or conventional) for up to 12 months. They had a validated Investigator’s Global Assessment of AD (vIGA-AD) score of 3 or 4 less than 45 days prior to initiation of systemic therapy or up to 14 days afterward. They also had at least one vIGA-AD assessment 3-12 months after initiating treatment. Outcome measures included IGA (defined as a score of 2 or less, with an optional target of 0 or 1), BSA (defined as a 50% BSA improvement, with an optimal target BSA of 2% or less), and the Worst-Itch Numeric Rating Scale (defined as at least a 4-point reduction, with an optimal target of 1 or less).

The analysis included 445 patients with a mean age of 31 years at enrollment. More than half (62%) were female and 45% were non-Hispanic Whites. Most patients (92%) were on an AST, mainly dupilumab, with smaller proportions treated with either tralokinumab, upadacitinib, or abrocitinib. Fewer than 10% of patients in the registry were being treated with CSTs.

At 6 months, 37% and approximately 67% of the AST-treated patients had inadequate responses in terms of skin clearance and itch outcomes, respectively. At 12 months, these figures were about 30% and 66%, respectively. CST-treated patients showed a similar trend. For patients starting an AST on or after Sept. 21, 2021, when three additional AST options were available (tralokinumab, upadacitinib, and abrocitinib), the proportion of patients demonstrating an adequate response over 12 months was generally similar to the overall cohort of those on ASTs.

“These findings suggest a need for alternative therapies and management strategies in AD treatment,” concluded Dr. Silverberg, who chaired the RAD symposium.

Dr. Silverberg reported being a consultant and/or an adviser for many pharmaceutical companies, and has received grant or research support from Galderma and Pfizer. The TARGET-DERM study is sponsored by Target PharmaSolutions.

A significant number of patients with moderate-to-severe atopic dermatitis (AD) failed to achieve adequate disease control with systemic therapies over 12 months in a study of patient registry data, indicating a substantial degree of “therapeutic inertia,” the study’s lead author, Jonathan I. Silverberg, MD, PhD, MPH, reported.

The findings come from an analysis of real-world outcomes from the TARGET-DERM AD registry, which Dr. Silverberg, professor and director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. He characterized the findings as “patients just getting stuck with a therapy and not advancing when they need to.”

TARGET-DERM AD is a longitudinal observational study of people with AD at 39 academic centers in the United States and Canada. Dr. Silverberg and his coinvestigators evaluated the proportion of patients who were experiencing an inadequate response after receiving systemic therapy and continuing on the same treatment for 3-12 months. “These are patients who are receiving their first or advanced systemic therapy, and the question is, how long did they stay on it, even if they’re not doing so well?” Dr. Silverberg said.

The researchers identified and compared the proportions of patients not achieving moderate or optimal clinician-reported outcome targets on patients with AD treated with their first systemic therapy. Advanced systemic therapy (AST) included abrocitinib, dupilumab, tralokinumab, or upadacitinib, while conventional systemic therapy (CST) included methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, and systemic corticosteroids.

Patients in TARGET-DERM AD were treated and maintained on their first systemic therapy (either advanced or conventional) for up to 12 months. They had a validated Investigator’s Global Assessment of AD (vIGA-AD) score of 3 or 4 less than 45 days prior to initiation of systemic therapy or up to 14 days afterward. They also had at least one vIGA-AD assessment 3-12 months after initiating treatment. Outcome measures included IGA (defined as a score of 2 or less, with an optional target of 0 or 1), BSA (defined as a 50% BSA improvement, with an optimal target BSA of 2% or less), and the Worst-Itch Numeric Rating Scale (defined as at least a 4-point reduction, with an optimal target of 1 or less).

The analysis included 445 patients with a mean age of 31 years at enrollment. More than half (62%) were female and 45% were non-Hispanic Whites. Most patients (92%) were on an AST, mainly dupilumab, with smaller proportions treated with either tralokinumab, upadacitinib, or abrocitinib. Fewer than 10% of patients in the registry were being treated with CSTs.

At 6 months, 37% and approximately 67% of the AST-treated patients had inadequate responses in terms of skin clearance and itch outcomes, respectively. At 12 months, these figures were about 30% and 66%, respectively. CST-treated patients showed a similar trend. For patients starting an AST on or after Sept. 21, 2021, when three additional AST options were available (tralokinumab, upadacitinib, and abrocitinib), the proportion of patients demonstrating an adequate response over 12 months was generally similar to the overall cohort of those on ASTs.

“These findings suggest a need for alternative therapies and management strategies in AD treatment,” concluded Dr. Silverberg, who chaired the RAD symposium.

Dr. Silverberg reported being a consultant and/or an adviser for many pharmaceutical companies, and has received grant or research support from Galderma and Pfizer. The TARGET-DERM study is sponsored by Target PharmaSolutions.

SAN DIEGO — Clinically significant interstitial lung disease (ILD) is believed to occur in 5%-10% of patients with rheumatoid arthritis (RA), but robust data are lacking on how to best predict which patients face the highest risk for RA-associated ILD. However, the results of several studies presented at the American College of Rheumatology annual meeting indicate that researchers are making strides in this field of rheumatologic care.

Adding Genetic Factors Improves ILD Risk Prediction

In the realm of risk stratification, Austin M. Wheeler, MD, a rheumatology fellow at the University of Nebraska Medical Center, Omaha, discussed the development and validation of a combined clinical and genetic risk score for ILD. “There is clear and well documented phenotypic and genetic overlap of ILD with idiopathic pulmonary fibrosis (IPF),” Dr. Wheeler said. “A number of clinical risk factors have been described for RA-ILD, including older age, male sex, smoking history, higher disease activity, and seropositivity. There are also well-documented genetic risk factors for RA-ILD. The MUC5B genetic variant is the strongest risk factor for IPF, and it’s been described in RA-ILD as well.”

Dr. Wheeler

A recently published study indicated that a genetic risk score without the MUC5B variant improved predictive ability for IPF and interstitial lung abnormalities better than using the MUC5B variant alone, “but no prior attempts have been made at developing a composite genetic risk score in RA-ILD” using both genetic and clinical risk factors, he said.

For the current study, Dr. Wheeler and colleagues drew from 2,386 participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a multicenter, prospective cohort of US veterans with rheumatologist-diagnosed RA and who fulfilled the 1987 ACR classification criteria. The researchers validated ILD through a systematic review of medical records, including clinical diagnosis of ILD plus either imaging or lung biopsy findings, and collected whole genome data that included 12 single nucleotide polymorphisms (SNPs) previously identified to be associated with risk for RA-ILD. They then used a meta-analytic approach to create pooled associations for each of those respective SNPs using data from the VARA registry participants as well as participants from the past study where the SNPs were first identified. “Those pooled associations were what we used for our effects size within the genetic risk score,” which ended up using five of the SNPs, Dr. Wheeler explained. Next, he and his colleagues combined the genetic risk score with clinical risk factors including age, sex, smoking history, disease activity, and rheumatoid factor (RF) positivity to create their combined risk score.

The mean age of the cohort was 70 years, 89% were male, 78% had a smoking history, and 78% were anti–cyclic citrullinated peptide (CCP) antibody positive. Of the 2,386 participants, 224 (9.4%) had RA-ILD. The full composite risk score had the highest area under the receiver operating curve (AUC) of 0.67, compared with an AUC of 0.623 using the clinical factors alone, 0.651 using the clinical factors plus only the MUC5B variant, and 0.654 using the composite score minus only the MUC5B variant. These AUCs show that “the combined risk score performs better than clinical factors even without the inclusion of the MUC5B variant in the score, which is notable because it supports the importance of further investigation into polygenic risk scores in RA-ILD as there is clearly more at play in a patient’s overall genetic risk,” Dr. Wheeler said.

As an example of the composite score’s ability to discriminate between people with and without RA-ILD, a cutpoint of 0.05 gave a sensitivity of 90.2% and would have eliminated about 25% of the cohort from unnecessary high-resolution CT scans and pulmonary function tests, he said.

“This study demonstrates the potential utility of genetic risk scores in RA-ILD identification and supports further investigation into individual risk stratification and screening,” he concluded. “This isn’t ready for clinical applicability by any means, but I think it serves as a proof of concept of the idea of a genetic risk score in RA-ILD.”

Biomarker Score Investigated

In a separate abstract, Brent Luedders, MD, assistant professor of rheumatology and immunology at the University of Nebraska Medical Center, and colleagues set out to determine if a previously derived biomarker score is associated with prevalent and incident ILD in the same VARA Registry cohort. An abstract presented at the ACR 2022 annual meeting found that a panel derived from IPF peripheral biomarkers was significantly associated with RA-ILD, including matrix metalloproteinase (MMP)-2, -7, and -9, eotaxin, macrophage-derived chemokine (MDC), monocyte chemoattractant protein-1 (MCP-1), fms-like tyrosine kinase 3 ligand (Flt3L) and interleukin-8 (IL-8). For the current analysis, Dr. Luedders and colleagues measured the concentrations of seven biomarkers (MMP-7, MMP-9, eotaxin, MDC, MCP-1, Flt3L, IL-8) from serum/plasma samples collected from VARA’s participants at enrollment to develop a score based on the concentrations of each biomarker.

Dr. Luedders

Baseline characteristics were similar between the groups, although those with prevalent RA-ILD were slightly older than those without ILD, and those who developed incident ILD during follow-up had slightly higher RA disease activity at the time of enrollment. When the researchers examined the association of the biomarker score with prevalent RA-ILD as a continuous measure, they found an adjusted OR of 1.08 for prevalent RA-ILD for each 1-point increase in the biomarker score. “When this was divided into quartiles, we found that the highest quartile of the biomarker score was associated with an adjusted odds ratio of 2.31 for prevalent RA-ILD,” Dr. Luedders said. “We saw a significant P for trend of < .001, suggesting a dose-response relationship, in which higher scores had higher risk.” Similar associations were observed for incident RA-ILD, in which participants with the highest quartile had an adjusted hazard ratio of 2.26 for incident RA-ILD.

The AUC of 0.653 that was obtained with clinical factors did not significantly improve with inclusion of the biomarker score, rising to only 0.669. “In receiver operating characteristic analysis, the addition of the biomarker score to clinical variables (age, sex, race, smoking status, anti-CCP positivity, and RA disease activity by DAS28) did not lead to a significant increase in the area under the curve. Therefore, further work is needed to identify combinations of clinical, biomarker, and other factors to accurately predict which people with RA will develop ILD,” he said.

Dr. Luedders acknowledged certain limitations of the results, including the fact that MMP-2 was not measured in this cohort and thus not included in the score. “This was an observational study with usual care; therefore, the absence of systemic evaluation for ILD may miss early or mild RA-ILD cases,” he added. “Similarly, a male predominance may limit the generalizability, and we have limited information on the RA-ILD pattern.” He concluded that the study results “support the shared pathogenesis of IPF and RA-ILD. However, we found that this score has limited discriminative performance, compared to clinical risk factors alone.”
 

Drilling Down on ILD Subtypes

In a poster abstract presentation at the meeting, Gregory Campbell McDermott, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, highlighted results from a study that investigated differences in demographic, serologic, and lifestyle factors for RA-ILD and the major subtypes of RA-ILD: usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). “Historically, RA-ILD has been studied as a single entity, even though we increasingly recognized that there are lots of different subtypes that fall under the umbrella of RA-ILD,” Dr. McDermott said in an interview. “We are also learning that the different subtypes probably have both prognostic and potentially therapeutic implications. For example, the UIP subtype, which is the most fibrotic subtype, has the worst prognosis but also may be a potential target for antifibrotic therapies. We’ve been trying to see if we can identify factors that are associated with specific subtypes, in particular the UIP subtype which has the worst prognosis.”

Dr. McDermott

He and his colleagues examined 208 patients with RA-ILD with a mean age of 51 years and 547 patients with RA but no ILD with a mean age of 49 years from two RA cohorts comprising 3,328 patients: the Mass General Brigham Biobank RA Cohort and the Brigham RA Sequential Study (BRASS). Of the 208 RA-ILD cases, nearly half (48%) were RA-UIP, 18% were RA-NSIP, 8% were organizing pneumonia, 3% were respiratory bronchiolitis-ILD, and 23% were other/indeterminate. After conducting multivariable adjusted analyses, the researchers found that RA-ILD was associated with male sex (OR, 1.58; 95% CI, 1.09-2.23), seropositivity for RF and/or anti-CCP (OR, 2.22; 95% CI, 1.51-3.24) and being an ever smoker (OR, 1.70; 95% CI, 1.13-2.54). Having all three of these risk factors was strongly associated with RA-ILD (OR, 6.04; 95% CI, 2.92-12.47) and with RA-UIP in particular (OR, 7.1). “We found that a lot of the traditional RA-ILD risk factors like male sex, history of smoking, and seropositive status were most strongly associated with a UIP pattern,” Dr. McDermott said. “We think this is a first step in trying to understand how these different ILD subtypes may have different risk factors, pathogenesis, and potentially different treatments, prevention, and screening strategies.”

While clinicians wait for guidelines on systemic autoimmune rheumatic disease-associated ILD that are expected to be published by the ACR in 2024, he added that “we probably shouldn’t screen every single person with RA for ILD, but we need to identify people who have symptoms or findings on clinical exam. This study wasn’t designed to look specifically at who is at high risk, but I think we are moving toward that question: Who is high risk, and who’s asymptomatic [but] may need more screening?”

He pointed out limitations of the study, including its retrospective design and the fact that imaging was done for clinical purposes, “so it’s probably a higher risk group to begin with than the whole RA population,” he said. “We also didn’t have data on RA disease activity or erosions, some of these other measures that we think are important for understanding the full RA disease phenotype in these patients.”

Dr. Wheeler reported having no disclosures. Dr. Luedders reported that his study was supported by the VA, the Rheumatology Research Foundation, and the University of Nebraska Medical Center Mentored Scholars Program. Dr. McDermott reported that his study was supported by the Rheumatology Research Foundation.

SAN DIEGO — Clinically significant interstitial lung disease (ILD) is believed to occur in 5%-10% of patients with rheumatoid arthritis (RA), but robust data are lacking on how to best predict which patients face the highest risk for RA-associated ILD. However, the results of several studies presented at the American College of Rheumatology annual meeting indicate that researchers are making strides in this field of rheumatologic care.

Adding Genetic Factors Improves ILD Risk Prediction

In the realm of risk stratification, Austin M. Wheeler, MD, a rheumatology fellow at the University of Nebraska Medical Center, Omaha, discussed the development and validation of a combined clinical and genetic risk score for ILD. “There is clear and well documented phenotypic and genetic overlap of ILD with idiopathic pulmonary fibrosis (IPF),” Dr. Wheeler said. “A number of clinical risk factors have been described for RA-ILD, including older age, male sex, smoking history, higher disease activity, and seropositivity. There are also well-documented genetic risk factors for RA-ILD. The MUC5B genetic variant is the strongest risk factor for IPF, and it’s been described in RA-ILD as well.”

Dr. Wheeler

A recently published study indicated that a genetic risk score without the MUC5B variant improved predictive ability for IPF and interstitial lung abnormalities better than using the MUC5B variant alone, “but no prior attempts have been made at developing a composite genetic risk score in RA-ILD” using both genetic and clinical risk factors, he said.

For the current study, Dr. Wheeler and colleagues drew from 2,386 participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a multicenter, prospective cohort of US veterans with rheumatologist-diagnosed RA and who fulfilled the 1987 ACR classification criteria. The researchers validated ILD through a systematic review of medical records, including clinical diagnosis of ILD plus either imaging or lung biopsy findings, and collected whole genome data that included 12 single nucleotide polymorphisms (SNPs) previously identified to be associated with risk for RA-ILD. They then used a meta-analytic approach to create pooled associations for each of those respective SNPs using data from the VARA registry participants as well as participants from the past study where the SNPs were first identified. “Those pooled associations were what we used for our effects size within the genetic risk score,” which ended up using five of the SNPs, Dr. Wheeler explained. Next, he and his colleagues combined the genetic risk score with clinical risk factors including age, sex, smoking history, disease activity, and rheumatoid factor (RF) positivity to create their combined risk score.

The mean age of the cohort was 70 years, 89% were male, 78% had a smoking history, and 78% were anti–cyclic citrullinated peptide (CCP) antibody positive. Of the 2,386 participants, 224 (9.4%) had RA-ILD. The full composite risk score had the highest area under the receiver operating curve (AUC) of 0.67, compared with an AUC of 0.623 using the clinical factors alone, 0.651 using the clinical factors plus only the MUC5B variant, and 0.654 using the composite score minus only the MUC5B variant. These AUCs show that “the combined risk score performs better than clinical factors even without the inclusion of the MUC5B variant in the score, which is notable because it supports the importance of further investigation into polygenic risk scores in RA-ILD as there is clearly more at play in a patient’s overall genetic risk,” Dr. Wheeler said.

As an example of the composite score’s ability to discriminate between people with and without RA-ILD, a cutpoint of 0.05 gave a sensitivity of 90.2% and would have eliminated about 25% of the cohort from unnecessary high-resolution CT scans and pulmonary function tests, he said.

“This study demonstrates the potential utility of genetic risk scores in RA-ILD identification and supports further investigation into individual risk stratification and screening,” he concluded. “This isn’t ready for clinical applicability by any means, but I think it serves as a proof of concept of the idea of a genetic risk score in RA-ILD.”

Biomarker Score Investigated

In a separate abstract, Brent Luedders, MD, assistant professor of rheumatology and immunology at the University of Nebraska Medical Center, and colleagues set out to determine if a previously derived biomarker score is associated with prevalent and incident ILD in the same VARA Registry cohort. An abstract presented at the ACR 2022 annual meeting found that a panel derived from IPF peripheral biomarkers was significantly associated with RA-ILD, including matrix metalloproteinase (MMP)-2, -7, and -9, eotaxin, macrophage-derived chemokine (MDC), monocyte chemoattractant protein-1 (MCP-1), fms-like tyrosine kinase 3 ligand (Flt3L) and interleukin-8 (IL-8). For the current analysis, Dr. Luedders and colleagues measured the concentrations of seven biomarkers (MMP-7, MMP-9, eotaxin, MDC, MCP-1, Flt3L, IL-8) from serum/plasma samples collected from VARA’s participants at enrollment to develop a score based on the concentrations of each biomarker.

Dr. Luedders

Baseline characteristics were similar between the groups, although those with prevalent RA-ILD were slightly older than those without ILD, and those who developed incident ILD during follow-up had slightly higher RA disease activity at the time of enrollment. When the researchers examined the association of the biomarker score with prevalent RA-ILD as a continuous measure, they found an adjusted OR of 1.08 for prevalent RA-ILD for each 1-point increase in the biomarker score. “When this was divided into quartiles, we found that the highest quartile of the biomarker score was associated with an adjusted odds ratio of 2.31 for prevalent RA-ILD,” Dr. Luedders said. “We saw a significant P for trend of < .001, suggesting a dose-response relationship, in which higher scores had higher risk.” Similar associations were observed for incident RA-ILD, in which participants with the highest quartile had an adjusted hazard ratio of 2.26 for incident RA-ILD.

The AUC of 0.653 that was obtained with clinical factors did not significantly improve with inclusion of the biomarker score, rising to only 0.669. “In receiver operating characteristic analysis, the addition of the biomarker score to clinical variables (age, sex, race, smoking status, anti-CCP positivity, and RA disease activity by DAS28) did not lead to a significant increase in the area under the curve. Therefore, further work is needed to identify combinations of clinical, biomarker, and other factors to accurately predict which people with RA will develop ILD,” he said.

Dr. Luedders acknowledged certain limitations of the results, including the fact that MMP-2 was not measured in this cohort and thus not included in the score. “This was an observational study with usual care; therefore, the absence of systemic evaluation for ILD may miss early or mild RA-ILD cases,” he added. “Similarly, a male predominance may limit the generalizability, and we have limited information on the RA-ILD pattern.” He concluded that the study results “support the shared pathogenesis of IPF and RA-ILD. However, we found that this score has limited discriminative performance, compared to clinical risk factors alone.”
 

Drilling Down on ILD Subtypes

In a poster abstract presentation at the meeting, Gregory Campbell McDermott, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, highlighted results from a study that investigated differences in demographic, serologic, and lifestyle factors for RA-ILD and the major subtypes of RA-ILD: usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). “Historically, RA-ILD has been studied as a single entity, even though we increasingly recognized that there are lots of different subtypes that fall under the umbrella of RA-ILD,” Dr. McDermott said in an interview. “We are also learning that the different subtypes probably have both prognostic and potentially therapeutic implications. For example, the UIP subtype, which is the most fibrotic subtype, has the worst prognosis but also may be a potential target for antifibrotic therapies. We’ve been trying to see if we can identify factors that are associated with specific subtypes, in particular the UIP subtype which has the worst prognosis.”

Dr. McDermott

He and his colleagues examined 208 patients with RA-ILD with a mean age of 51 years and 547 patients with RA but no ILD with a mean age of 49 years from two RA cohorts comprising 3,328 patients: the Mass General Brigham Biobank RA Cohort and the Brigham RA Sequential Study (BRASS). Of the 208 RA-ILD cases, nearly half (48%) were RA-UIP, 18% were RA-NSIP, 8% were organizing pneumonia, 3% were respiratory bronchiolitis-ILD, and 23% were other/indeterminate. After conducting multivariable adjusted analyses, the researchers found that RA-ILD was associated with male sex (OR, 1.58; 95% CI, 1.09-2.23), seropositivity for RF and/or anti-CCP (OR, 2.22; 95% CI, 1.51-3.24) and being an ever smoker (OR, 1.70; 95% CI, 1.13-2.54). Having all three of these risk factors was strongly associated with RA-ILD (OR, 6.04; 95% CI, 2.92-12.47) and with RA-UIP in particular (OR, 7.1). “We found that a lot of the traditional RA-ILD risk factors like male sex, history of smoking, and seropositive status were most strongly associated with a UIP pattern,” Dr. McDermott said. “We think this is a first step in trying to understand how these different ILD subtypes may have different risk factors, pathogenesis, and potentially different treatments, prevention, and screening strategies.”

While clinicians wait for guidelines on systemic autoimmune rheumatic disease-associated ILD that are expected to be published by the ACR in 2024, he added that “we probably shouldn’t screen every single person with RA for ILD, but we need to identify people who have symptoms or findings on clinical exam. This study wasn’t designed to look specifically at who is at high risk, but I think we are moving toward that question: Who is high risk, and who’s asymptomatic [but] may need more screening?”

He pointed out limitations of the study, including its retrospective design and the fact that imaging was done for clinical purposes, “so it’s probably a higher risk group to begin with than the whole RA population,” he said. “We also didn’t have data on RA disease activity or erosions, some of these other measures that we think are important for understanding the full RA disease phenotype in these patients.”

Dr. Wheeler reported having no disclosures. Dr. Luedders reported that his study was supported by the VA, the Rheumatology Research Foundation, and the University of Nebraska Medical Center Mentored Scholars Program. Dr. McDermott reported that his study was supported by the Rheumatology Research Foundation.

SAN DIEGO — Clinically significant interstitial lung disease (ILD) is believed to occur in 5%-10% of patients with rheumatoid arthritis (RA), but robust data are lacking on how to best predict which patients face the highest risk for RA-associated ILD. However, the results of several studies presented at the American College of Rheumatology annual meeting indicate that researchers are making strides in this field of rheumatologic care.

Adding Genetic Factors Improves ILD Risk Prediction

In the realm of risk stratification, Austin M. Wheeler, MD, a rheumatology fellow at the University of Nebraska Medical Center, Omaha, discussed the development and validation of a combined clinical and genetic risk score for ILD. “There is clear and well documented phenotypic and genetic overlap of ILD with idiopathic pulmonary fibrosis (IPF),” Dr. Wheeler said. “A number of clinical risk factors have been described for RA-ILD, including older age, male sex, smoking history, higher disease activity, and seropositivity. There are also well-documented genetic risk factors for RA-ILD. The MUC5B genetic variant is the strongest risk factor for IPF, and it’s been described in RA-ILD as well.”

Dr. Wheeler

A recently published study indicated that a genetic risk score without the MUC5B variant improved predictive ability for IPF and interstitial lung abnormalities better than using the MUC5B variant alone, “but no prior attempts have been made at developing a composite genetic risk score in RA-ILD” using both genetic and clinical risk factors, he said.

For the current study, Dr. Wheeler and colleagues drew from 2,386 participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a multicenter, prospective cohort of US veterans with rheumatologist-diagnosed RA and who fulfilled the 1987 ACR classification criteria. The researchers validated ILD through a systematic review of medical records, including clinical diagnosis of ILD plus either imaging or lung biopsy findings, and collected whole genome data that included 12 single nucleotide polymorphisms (SNPs) previously identified to be associated with risk for RA-ILD. They then used a meta-analytic approach to create pooled associations for each of those respective SNPs using data from the VARA registry participants as well as participants from the past study where the SNPs were first identified. “Those pooled associations were what we used for our effects size within the genetic risk score,” which ended up using five of the SNPs, Dr. Wheeler explained. Next, he and his colleagues combined the genetic risk score with clinical risk factors including age, sex, smoking history, disease activity, and rheumatoid factor (RF) positivity to create their combined risk score.

The mean age of the cohort was 70 years, 89% were male, 78% had a smoking history, and 78% were anti–cyclic citrullinated peptide (CCP) antibody positive. Of the 2,386 participants, 224 (9.4%) had RA-ILD. The full composite risk score had the highest area under the receiver operating curve (AUC) of 0.67, compared with an AUC of 0.623 using the clinical factors alone, 0.651 using the clinical factors plus only the MUC5B variant, and 0.654 using the composite score minus only the MUC5B variant. These AUCs show that “the combined risk score performs better than clinical factors even without the inclusion of the MUC5B variant in the score, which is notable because it supports the importance of further investigation into polygenic risk scores in RA-ILD as there is clearly more at play in a patient’s overall genetic risk,” Dr. Wheeler said.

As an example of the composite score’s ability to discriminate between people with and without RA-ILD, a cutpoint of 0.05 gave a sensitivity of 90.2% and would have eliminated about 25% of the cohort from unnecessary high-resolution CT scans and pulmonary function tests, he said.

“This study demonstrates the potential utility of genetic risk scores in RA-ILD identification and supports further investigation into individual risk stratification and screening,” he concluded. “This isn’t ready for clinical applicability by any means, but I think it serves as a proof of concept of the idea of a genetic risk score in RA-ILD.”

Biomarker Score Investigated

In a separate abstract, Brent Luedders, MD, assistant professor of rheumatology and immunology at the University of Nebraska Medical Center, and colleagues set out to determine if a previously derived biomarker score is associated with prevalent and incident ILD in the same VARA Registry cohort. An abstract presented at the ACR 2022 annual meeting found that a panel derived from IPF peripheral biomarkers was significantly associated with RA-ILD, including matrix metalloproteinase (MMP)-2, -7, and -9, eotaxin, macrophage-derived chemokine (MDC), monocyte chemoattractant protein-1 (MCP-1), fms-like tyrosine kinase 3 ligand (Flt3L) and interleukin-8 (IL-8). For the current analysis, Dr. Luedders and colleagues measured the concentrations of seven biomarkers (MMP-7, MMP-9, eotaxin, MDC, MCP-1, Flt3L, IL-8) from serum/plasma samples collected from VARA’s participants at enrollment to develop a score based on the concentrations of each biomarker.

Dr. Luedders

Baseline characteristics were similar between the groups, although those with prevalent RA-ILD were slightly older than those without ILD, and those who developed incident ILD during follow-up had slightly higher RA disease activity at the time of enrollment. When the researchers examined the association of the biomarker score with prevalent RA-ILD as a continuous measure, they found an adjusted OR of 1.08 for prevalent RA-ILD for each 1-point increase in the biomarker score. “When this was divided into quartiles, we found that the highest quartile of the biomarker score was associated with an adjusted odds ratio of 2.31 for prevalent RA-ILD,” Dr. Luedders said. “We saw a significant P for trend of < .001, suggesting a dose-response relationship, in which higher scores had higher risk.” Similar associations were observed for incident RA-ILD, in which participants with the highest quartile had an adjusted hazard ratio of 2.26 for incident RA-ILD.

The AUC of 0.653 that was obtained with clinical factors did not significantly improve with inclusion of the biomarker score, rising to only 0.669. “In receiver operating characteristic analysis, the addition of the biomarker score to clinical variables (age, sex, race, smoking status, anti-CCP positivity, and RA disease activity by DAS28) did not lead to a significant increase in the area under the curve. Therefore, further work is needed to identify combinations of clinical, biomarker, and other factors to accurately predict which people with RA will develop ILD,” he said.

Dr. Luedders acknowledged certain limitations of the results, including the fact that MMP-2 was not measured in this cohort and thus not included in the score. “This was an observational study with usual care; therefore, the absence of systemic evaluation for ILD may miss early or mild RA-ILD cases,” he added. “Similarly, a male predominance may limit the generalizability, and we have limited information on the RA-ILD pattern.” He concluded that the study results “support the shared pathogenesis of IPF and RA-ILD. However, we found that this score has limited discriminative performance, compared to clinical risk factors alone.”
 

Drilling Down on ILD Subtypes

In a poster abstract presentation at the meeting, Gregory Campbell McDermott, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, highlighted results from a study that investigated differences in demographic, serologic, and lifestyle factors for RA-ILD and the major subtypes of RA-ILD: usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). “Historically, RA-ILD has been studied as a single entity, even though we increasingly recognized that there are lots of different subtypes that fall under the umbrella of RA-ILD,” Dr. McDermott said in an interview. “We are also learning that the different subtypes probably have both prognostic and potentially therapeutic implications. For example, the UIP subtype, which is the most fibrotic subtype, has the worst prognosis but also may be a potential target for antifibrotic therapies. We’ve been trying to see if we can identify factors that are associated with specific subtypes, in particular the UIP subtype which has the worst prognosis.”

Dr. McDermott

He and his colleagues examined 208 patients with RA-ILD with a mean age of 51 years and 547 patients with RA but no ILD with a mean age of 49 years from two RA cohorts comprising 3,328 patients: the Mass General Brigham Biobank RA Cohort and the Brigham RA Sequential Study (BRASS). Of the 208 RA-ILD cases, nearly half (48%) were RA-UIP, 18% were RA-NSIP, 8% were organizing pneumonia, 3% were respiratory bronchiolitis-ILD, and 23% were other/indeterminate. After conducting multivariable adjusted analyses, the researchers found that RA-ILD was associated with male sex (OR, 1.58; 95% CI, 1.09-2.23), seropositivity for RF and/or anti-CCP (OR, 2.22; 95% CI, 1.51-3.24) and being an ever smoker (OR, 1.70; 95% CI, 1.13-2.54). Having all three of these risk factors was strongly associated with RA-ILD (OR, 6.04; 95% CI, 2.92-12.47) and with RA-UIP in particular (OR, 7.1). “We found that a lot of the traditional RA-ILD risk factors like male sex, history of smoking, and seropositive status were most strongly associated with a UIP pattern,” Dr. McDermott said. “We think this is a first step in trying to understand how these different ILD subtypes may have different risk factors, pathogenesis, and potentially different treatments, prevention, and screening strategies.”

While clinicians wait for guidelines on systemic autoimmune rheumatic disease-associated ILD that are expected to be published by the ACR in 2024, he added that “we probably shouldn’t screen every single person with RA for ILD, but we need to identify people who have symptoms or findings on clinical exam. This study wasn’t designed to look specifically at who is at high risk, but I think we are moving toward that question: Who is high risk, and who’s asymptomatic [but] may need more screening?”

He pointed out limitations of the study, including its retrospective design and the fact that imaging was done for clinical purposes, “so it’s probably a higher risk group to begin with than the whole RA population,” he said. “We also didn’t have data on RA disease activity or erosions, some of these other measures that we think are important for understanding the full RA disease phenotype in these patients.”

Dr. Wheeler reported having no disclosures. Dr. Luedders reported that his study was supported by the VA, the Rheumatology Research Foundation, and the University of Nebraska Medical Center Mentored Scholars Program. Dr. McDermott reported that his study was supported by the Rheumatology Research Foundation.

Tape stripping, which allows sampling of the epidermis to the midgranular layer, is a valid, minimally invasive way to identify cutaneous biomarkers in patients with hidradenitis suppurative (HS), results from a novel study showed.

“Tape strips can provide important clues to when and which drugs to use in HS in patients with both early and late disease, which can change clinical practice,” corresponding study author Emma Guttman-Yassky, MD, PhD, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai in New York City, said in an interview. “It is noninvasive and nonscarring,” she added.

Tape stripping has been validated in atopic dermatitis, psoriasis, and other dermatologic conditions in recent years. For the current study, which was published online in the Journal of the American Academy of Dermatology, and is believed to be the first of its kind, Dr. Guttman-Yassky and colleagues performed RNA sequencing from large D-Squame tape strips collected from lesional and nonlesional skin of 22 patients with HS and from 21 age- and sex-matched healthy controls. They correlated the expression of skin biomarkers between tape strips and a previously published gene-signature of HS biopsies. The mean age of patients with HS was 43 years, while the mean age of healthy controls was 35. The average International Hidradenitis Suppurativa Severity Score System (IHS4) score of the HS cohort was 36.

Consistent with published studies, the researchers found that tape strips identified an overall higher inflammatory burden in HS. Specifically, they observed an upregulation of known cytokines within the following pathways: Th1 (such as IFNG, CXCL9/10/11, and CCR5); Th17 (such as interleukin [IL]-17A/F, IL12B, IL23A, CAMP, and CCL20); Th2 (such as IL4R, IL13/IL31/IL10, CCR4, CCL7/CCL13/CCL24, TNFSF4/OX40L, and TNFRSF4/OX40); and Th22 (such as IL22 and IL32).

The researchers also found that the expression of Th17 and tumor necrosis factor (TNF)–alpha pathways were highly correlated between tape strips and biopsies and that HS clinical severity was significantly associated with expression of biomarkers, such as TNF-alpha, IL17A/F, OX40, JAK1-3, and IL4R in HS lesional and/or nonlesional skin.

“It was quite unexpected that we are able to identify, using a minimally invasive approach that samples only the upper layers of the epidermis, products and processes that are considered to be deeper-situated, such as IL-17, and other immune markers,” Dr. Guttman-Yassky said in the interview. “We were also surprised to see how well the tape-stripped–derived skin molecular profile correlated with that of biopsies, as well as how well it correlated with the clinical disease severity of HS.”

Also surprising, she added, was that the biomarkers in nonlesional tape-stripped skin, such as IL-17 and TNF alpha, “show high correlations with disease severity and provide clues to early disease.”

If using tape strips in HS is validated in larger cohort studies, the potential cost implications of using this approach in practice remain unclear, Dr. Guttman-Yassky said. “It is currently not cheap, but we are hoping that one day, we can provide a means to diagnose the disease and treat it early, and appropriately, utilizing this approach,” she commented. “We are excited about the applicability of this study to the early treatment and longitudinal follow up of HS with drugs that are targeting specific immune molecules and pathways,” she said, adding that it will also be useful for helping determine which drug should be used for which patient.

She and her co-authors acknowledged certain limitations of the study, including its small sample size and the fact that tape stripping is limited to the epidermis.

Asked to comment on the study, Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, said the findings “have important potential implications for our ability to one day personalize treatments for a patient with early HS in a minimally invasive way.”

As the study authors point out, she added, “tape strips only allow sampling of the epidermis, which is limiting in a disease like HS where much of the disruption is in the dermis with deep nodules and dermal tunnels. However, our overall goal should be to catch patients in the early stages of their disease before the occurrence of irreversible tissue damage such as dermal tunnels. Thus, the ongoing campaign for early diagnosis and early intervention by various stakeholders in the field of HS can help mitigate the impact of this inherent limitation of tape strips. It will be exciting to see larger studies that investigate tape strip results in relation to clinical phenotypes, disease progression, and therapeutic responses.”

The study was funded by an International Dermatology Outcome Measures Hidradenitis Suppurativa Grant. Dr. Guttman-Yassky disclosed that she has been a consultant to, an adviser for, and has received research grants from many pharmaceutical companies. Of the remaining authors, 2 also had multiple disclosures and 11 had no disclosures. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

Tape stripping, which allows sampling of the epidermis to the midgranular layer, is a valid, minimally invasive way to identify cutaneous biomarkers in patients with hidradenitis suppurative (HS), results from a novel study showed.

“Tape strips can provide important clues to when and which drugs to use in HS in patients with both early and late disease, which can change clinical practice,” corresponding study author Emma Guttman-Yassky, MD, PhD, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai in New York City, said in an interview. “It is noninvasive and nonscarring,” she added.

Tape stripping has been validated in atopic dermatitis, psoriasis, and other dermatologic conditions in recent years. For the current study, which was published online in the Journal of the American Academy of Dermatology, and is believed to be the first of its kind, Dr. Guttman-Yassky and colleagues performed RNA sequencing from large D-Squame tape strips collected from lesional and nonlesional skin of 22 patients with HS and from 21 age- and sex-matched healthy controls. They correlated the expression of skin biomarkers between tape strips and a previously published gene-signature of HS biopsies. The mean age of patients with HS was 43 years, while the mean age of healthy controls was 35. The average International Hidradenitis Suppurativa Severity Score System (IHS4) score of the HS cohort was 36.

Consistent with published studies, the researchers found that tape strips identified an overall higher inflammatory burden in HS. Specifically, they observed an upregulation of known cytokines within the following pathways: Th1 (such as IFNG, CXCL9/10/11, and CCR5); Th17 (such as interleukin [IL]-17A/F, IL12B, IL23A, CAMP, and CCL20); Th2 (such as IL4R, IL13/IL31/IL10, CCR4, CCL7/CCL13/CCL24, TNFSF4/OX40L, and TNFRSF4/OX40); and Th22 (such as IL22 and IL32).

The researchers also found that the expression of Th17 and tumor necrosis factor (TNF)–alpha pathways were highly correlated between tape strips and biopsies and that HS clinical severity was significantly associated with expression of biomarkers, such as TNF-alpha, IL17A/F, OX40, JAK1-3, and IL4R in HS lesional and/or nonlesional skin.

“It was quite unexpected that we are able to identify, using a minimally invasive approach that samples only the upper layers of the epidermis, products and processes that are considered to be deeper-situated, such as IL-17, and other immune markers,” Dr. Guttman-Yassky said in the interview. “We were also surprised to see how well the tape-stripped–derived skin molecular profile correlated with that of biopsies, as well as how well it correlated with the clinical disease severity of HS.”

Also surprising, she added, was that the biomarkers in nonlesional tape-stripped skin, such as IL-17 and TNF alpha, “show high correlations with disease severity and provide clues to early disease.”

If using tape strips in HS is validated in larger cohort studies, the potential cost implications of using this approach in practice remain unclear, Dr. Guttman-Yassky said. “It is currently not cheap, but we are hoping that one day, we can provide a means to diagnose the disease and treat it early, and appropriately, utilizing this approach,” she commented. “We are excited about the applicability of this study to the early treatment and longitudinal follow up of HS with drugs that are targeting specific immune molecules and pathways,” she said, adding that it will also be useful for helping determine which drug should be used for which patient.

She and her co-authors acknowledged certain limitations of the study, including its small sample size and the fact that tape stripping is limited to the epidermis.

Asked to comment on the study, Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, said the findings “have important potential implications for our ability to one day personalize treatments for a patient with early HS in a minimally invasive way.”

As the study authors point out, she added, “tape strips only allow sampling of the epidermis, which is limiting in a disease like HS where much of the disruption is in the dermis with deep nodules and dermal tunnels. However, our overall goal should be to catch patients in the early stages of their disease before the occurrence of irreversible tissue damage such as dermal tunnels. Thus, the ongoing campaign for early diagnosis and early intervention by various stakeholders in the field of HS can help mitigate the impact of this inherent limitation of tape strips. It will be exciting to see larger studies that investigate tape strip results in relation to clinical phenotypes, disease progression, and therapeutic responses.”

The study was funded by an International Dermatology Outcome Measures Hidradenitis Suppurativa Grant. Dr. Guttman-Yassky disclosed that she has been a consultant to, an adviser for, and has received research grants from many pharmaceutical companies. Of the remaining authors, 2 also had multiple disclosures and 11 had no disclosures. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

Tape stripping, which allows sampling of the epidermis to the midgranular layer, is a valid, minimally invasive way to identify cutaneous biomarkers in patients with hidradenitis suppurative (HS), results from a novel study showed.

“Tape strips can provide important clues to when and which drugs to use in HS in patients with both early and late disease, which can change clinical practice,” corresponding study author Emma Guttman-Yassky, MD, PhD, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai in New York City, said in an interview. “It is noninvasive and nonscarring,” she added.

Tape stripping has been validated in atopic dermatitis, psoriasis, and other dermatologic conditions in recent years. For the current study, which was published online in the Journal of the American Academy of Dermatology, and is believed to be the first of its kind, Dr. Guttman-Yassky and colleagues performed RNA sequencing from large D-Squame tape strips collected from lesional and nonlesional skin of 22 patients with HS and from 21 age- and sex-matched healthy controls. They correlated the expression of skin biomarkers between tape strips and a previously published gene-signature of HS biopsies. The mean age of patients with HS was 43 years, while the mean age of healthy controls was 35. The average International Hidradenitis Suppurativa Severity Score System (IHS4) score of the HS cohort was 36.

Consistent with published studies, the researchers found that tape strips identified an overall higher inflammatory burden in HS. Specifically, they observed an upregulation of known cytokines within the following pathways: Th1 (such as IFNG, CXCL9/10/11, and CCR5); Th17 (such as interleukin [IL]-17A/F, IL12B, IL23A, CAMP, and CCL20); Th2 (such as IL4R, IL13/IL31/IL10, CCR4, CCL7/CCL13/CCL24, TNFSF4/OX40L, and TNFRSF4/OX40); and Th22 (such as IL22 and IL32).

The researchers also found that the expression of Th17 and tumor necrosis factor (TNF)–alpha pathways were highly correlated between tape strips and biopsies and that HS clinical severity was significantly associated with expression of biomarkers, such as TNF-alpha, IL17A/F, OX40, JAK1-3, and IL4R in HS lesional and/or nonlesional skin.

“It was quite unexpected that we are able to identify, using a minimally invasive approach that samples only the upper layers of the epidermis, products and processes that are considered to be deeper-situated, such as IL-17, and other immune markers,” Dr. Guttman-Yassky said in the interview. “We were also surprised to see how well the tape-stripped–derived skin molecular profile correlated with that of biopsies, as well as how well it correlated with the clinical disease severity of HS.”

Also surprising, she added, was that the biomarkers in nonlesional tape-stripped skin, such as IL-17 and TNF alpha, “show high correlations with disease severity and provide clues to early disease.”

If using tape strips in HS is validated in larger cohort studies, the potential cost implications of using this approach in practice remain unclear, Dr. Guttman-Yassky said. “It is currently not cheap, but we are hoping that one day, we can provide a means to diagnose the disease and treat it early, and appropriately, utilizing this approach,” she commented. “We are excited about the applicability of this study to the early treatment and longitudinal follow up of HS with drugs that are targeting specific immune molecules and pathways,” she said, adding that it will also be useful for helping determine which drug should be used for which patient.

She and her co-authors acknowledged certain limitations of the study, including its small sample size and the fact that tape stripping is limited to the epidermis.

Asked to comment on the study, Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, said the findings “have important potential implications for our ability to one day personalize treatments for a patient with early HS in a minimally invasive way.”

As the study authors point out, she added, “tape strips only allow sampling of the epidermis, which is limiting in a disease like HS where much of the disruption is in the dermis with deep nodules and dermal tunnels. However, our overall goal should be to catch patients in the early stages of their disease before the occurrence of irreversible tissue damage such as dermal tunnels. Thus, the ongoing campaign for early diagnosis and early intervention by various stakeholders in the field of HS can help mitigate the impact of this inherent limitation of tape strips. It will be exciting to see larger studies that investigate tape strip results in relation to clinical phenotypes, disease progression, and therapeutic responses.”

The study was funded by an International Dermatology Outcome Measures Hidradenitis Suppurativa Grant. Dr. Guttman-Yassky disclosed that she has been a consultant to, an adviser for, and has received research grants from many pharmaceutical companies. Of the remaining authors, 2 also had multiple disclosures and 11 had no disclosures. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

TOPLINE:

Patients with psoriasis had a 1.77-fold increased risk of having obstructive sleep apnea, in a study comparing patients with psoriasis with controls.

METHODOLOGY:

• Prior studies have established a link between psoriasis and obstructive sleep apnea (OSA), but some have suggested that confounders may drive the association.
• Using a case-control design, researchers analyzed data from 156,707 participants in the National Institutes of Health’s : 5140 with psoriasis and 151,567 controls.
• They used Pearson’s x 2 test to compare the prevalence of OSA among cases and controls, logistic regression to calculate odds ratios (ORs) in multivariable analysis, and two-sided t-tests to evaluate the significance between continuous variables.

TAKEAWAY:

• Compared with controls, patients with psoriasis were older (a mean of 62.4 vs 57.3 years, respectively), more likely to be White (86.1% vs 70.6%), reported higher annual household incomes (59.9% vs 52.6%), and were more likely to smoke (48.2% vs 43.4%).
• The rate of OSA was significantly higher among patients with psoriasis compared with controls (29.3% vs 17.1%; P < .001).
• On unadjusted multivariable logistic regression controlling for age, gender, and race, psoriasis was significantly associated with OSA (OR, 1.77, 95% CI, 1.66 - 1.89; P < .001).
• Psoriasis was also significantly associated with OSA in the adjusted model controlling for age, gender, race, BMI, and smoking status (OR, 1.66, 95% CI, 1.55 - 1.77; P < .001) and in the adjusted model controlling for age, gender, race, BMI, smoking status, type 2 diabetes, congestive heart failure, hypertension, history of myocardial infarction, angina, and peripheral artery disease (OR, 1.45, 95% CI, 1.35 - 1.55; P <.001).

IN PRACTICE:

“This study further substantiates the association between psoriasis and OSA, reinforcing the importance of evaluation for OSA when clinically appropriate given that both psoriasis and OSA contribute to adverse health outcomes,” the authors conclude.

SOURCE:

Corresponding author Jeffrey M. Cohen, MD, of the Department of Dermatology at Yale University, New Haven, Connecticut, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included the use of electronic health record data, a potential lack of generalizability to the US population, and reliance on survey data for certain variables such as income and smoking status.

DISCLOSURES:

The All of Us Research Program is supported by the National Institutes of Health. Cohen disclosed that he serves on a data safety and monitoring board for Advarra.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with psoriasis had a 1.77-fold increased risk of having obstructive sleep apnea, in a study comparing patients with psoriasis with controls.

METHODOLOGY:

• Prior studies have established a link between psoriasis and obstructive sleep apnea (OSA), but some have suggested that confounders may drive the association.
• Using a case-control design, researchers analyzed data from 156,707 participants in the National Institutes of Health’s : 5140 with psoriasis and 151,567 controls.
• They used Pearson’s x 2 test to compare the prevalence of OSA among cases and controls, logistic regression to calculate odds ratios (ORs) in multivariable analysis, and two-sided t-tests to evaluate the significance between continuous variables.

TAKEAWAY:

• Compared with controls, patients with psoriasis were older (a mean of 62.4 vs 57.3 years, respectively), more likely to be White (86.1% vs 70.6%), reported higher annual household incomes (59.9% vs 52.6%), and were more likely to smoke (48.2% vs 43.4%).
• The rate of OSA was significantly higher among patients with psoriasis compared with controls (29.3% vs 17.1%; P < .001).
• On unadjusted multivariable logistic regression controlling for age, gender, and race, psoriasis was significantly associated with OSA (OR, 1.77, 95% CI, 1.66 - 1.89; P < .001).
• Psoriasis was also significantly associated with OSA in the adjusted model controlling for age, gender, race, BMI, and smoking status (OR, 1.66, 95% CI, 1.55 - 1.77; P < .001) and in the adjusted model controlling for age, gender, race, BMI, smoking status, type 2 diabetes, congestive heart failure, hypertension, history of myocardial infarction, angina, and peripheral artery disease (OR, 1.45, 95% CI, 1.35 - 1.55; P <.001).

IN PRACTICE:

“This study further substantiates the association between psoriasis and OSA, reinforcing the importance of evaluation for OSA when clinically appropriate given that both psoriasis and OSA contribute to adverse health outcomes,” the authors conclude.

SOURCE:

Corresponding author Jeffrey M. Cohen, MD, of the Department of Dermatology at Yale University, New Haven, Connecticut, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included the use of electronic health record data, a potential lack of generalizability to the US population, and reliance on survey data for certain variables such as income and smoking status.

DISCLOSURES:

The All of Us Research Program is supported by the National Institutes of Health. Cohen disclosed that he serves on a data safety and monitoring board for Advarra.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with psoriasis had a 1.77-fold increased risk of having obstructive sleep apnea, in a study comparing patients with psoriasis with controls.

METHODOLOGY:

• Prior studies have established a link between psoriasis and obstructive sleep apnea (OSA), but some have suggested that confounders may drive the association.
• Using a case-control design, researchers analyzed data from 156,707 participants in the National Institutes of Health’s : 5140 with psoriasis and 151,567 controls.
• They used Pearson’s x 2 test to compare the prevalence of OSA among cases and controls, logistic regression to calculate odds ratios (ORs) in multivariable analysis, and two-sided t-tests to evaluate the significance between continuous variables.

TAKEAWAY:

• Compared with controls, patients with psoriasis were older (a mean of 62.4 vs 57.3 years, respectively), more likely to be White (86.1% vs 70.6%), reported higher annual household incomes (59.9% vs 52.6%), and were more likely to smoke (48.2% vs 43.4%).
• The rate of OSA was significantly higher among patients with psoriasis compared with controls (29.3% vs 17.1%; P < .001).
• On unadjusted multivariable logistic regression controlling for age, gender, and race, psoriasis was significantly associated with OSA (OR, 1.77, 95% CI, 1.66 - 1.89; P < .001).
• Psoriasis was also significantly associated with OSA in the adjusted model controlling for age, gender, race, BMI, and smoking status (OR, 1.66, 95% CI, 1.55 - 1.77; P < .001) and in the adjusted model controlling for age, gender, race, BMI, smoking status, type 2 diabetes, congestive heart failure, hypertension, history of myocardial infarction, angina, and peripheral artery disease (OR, 1.45, 95% CI, 1.35 - 1.55; P <.001).

IN PRACTICE:

“This study further substantiates the association between psoriasis and OSA, reinforcing the importance of evaluation for OSA when clinically appropriate given that both psoriasis and OSA contribute to adverse health outcomes,” the authors conclude.

SOURCE:

Corresponding author Jeffrey M. Cohen, MD, of the Department of Dermatology at Yale University, New Haven, Connecticut, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included the use of electronic health record data, a potential lack of generalizability to the US population, and reliance on survey data for certain variables such as income and smoking status.

DISCLOSURES:

The All of Us Research Program is supported by the National Institutes of Health. Cohen disclosed that he serves on a data safety and monitoring board for Advarra.

A version of this article appeared on Medscape.com.

SAN DIEGO — Women with autoimmune skin diseases are at increased risk of adverse pregnancy outcomes and may benefit from multidisciplinary care with maternal-fetal medicine specialists, results from a large case-control study suggest.

Patients with systemic autoimmune conditions are known to have an increased risk for adverse pregnancy outcomes, “but we weren’t sure if that was the case for patients with autoimmune skin conditions,” presenting study author Heejo Keum, a fourth-year medical student at the University of Texas Southwestern Medical Center, Dallas, said in an interview during a poster session at the American College of Rheumatology (ACR) 2023 annual meeting. “There are case reports or nationwide population-based studies on patients with alopecia areata and vitiligo, but those were outside of the US, so we wanted to see if these outcomes could be studied in a larger population-based study in the US.”

Doug Brunk/MDedge News

Drawing from the TriNetX US Collaborative Network, a database of electronic medical records of 94 million patients in the United States, the researchers identified pregnant patients aged 15-44 years between January 1, 2016, and December 31, 2021. Cases were defined as patients diagnosed with at least one autoimmune skin disease (ASD) prior to the end of pregnancy, including alopecia areata, bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, cutaneous lupus erythematosus, epidermolysis bullosa acquisita, morphea, pemphigus foliaceus, pemphigus vulgaris, vitiligo, and amyopathic DM. There were two control groups: healthy controls (those without ASDs, systemic lupus erythematosus or rheumatoid arthritis) and disease controls (those with SLE or RA). The researchers used ICD-10 codes to identify pregnancy endpoints, including live births, spontaneous abortion, and stillbirth. Patients with a history of hidradenitis suppurative were excluded from the analysis, as were those with common autoimmune disease such as Hashimoto’s thyroiditis, Grave’s disease, and type 1 diabetes.

The primary outcomes were adverse pregnancy outcomes defined as spontaneous abortion, gestational hypertension, preeclampsia/eclampsia, gestational diabetes, intrauterine growth restriction (IUGR), preterm premature rupture of membranes (PPROM), and preterm birth. The researchers used 1:1 propensity scoring to match patients with ASDs to controls by age, race, ethnicity, comorbidities, obesity, and substance use, and used odds ratio (OR) analysis with a 95% confidence interval (CI) to calculate each outcome.

Ms. Keum reported results from 3,654 women with ASDs, 3,654 healthy controls, 2,147 women with SLE, and 889 women with RA.

The three most common ASDs were vitiligo (30%), alopecia areata (30%), and cutaneous lupus erythematosus (27%). Compared with healthy controls, patients with ASDs were more likely to have spontaneous abortions (OR=1.5 [1.4-1.7], P<.001), and preeclampsia/eclampsia (OR=1.2 [1.0-1.3], P=.04). Compared with women with SLE, women with ASDs were less likely to have preeclampsia/eclampsia (OR=0.7 [0.6-0.9, P=.001); preterm birth (OR= 0.5 [0.4-0.7], P<.001); PPROM (OR=0.6 [0.4-0.9], P=.004), or an infant with IUGR (OR=0.6 [0.5-0.8], P<.001), but they were more likely to have a spontaneous abortion (OR=1.2 [1.1-1.3], P=.003). Overall, patients with ASDs had similar risks for adverse pregnancy outcomes as patients with RA.

“We found that patients with cutaneous lupus and vitiligo had higher rates of spontaneous abortion, which is interesting because we didn’t expect that,” Ms. Keum told this news organization. “Studies have shown that vitiligo patients might have an increased risk of pregnancy loss, so I think it’s important to have that discussion with those patients. It might benefit them to talk to a maternal-fetal medicine specialist. As for next steps, we want to look at how medication use and disease flare or disease severity play a role in APOs.”

In their poster, the researchers acknowledged limitations of the study, including the inability to verify diagnoses or assess disease severity. Also, while medication use and concomitant antiphospholipid syndrome were evaluated as risk factors for advanced pregnancy outcomes, the number of patients per group was too small for analysis.

Karl Saardi, MD, director of the inpatient dermatology service at George Washington University Hospital, Washington, who was asked to comment on the study, said that in his view, the choice of disease states included in the analysis “is a bit arbitrary.” He added that “it would have been more helpful to compare controls versus discoid lupus versus systemic lupus or controls versus amyopathic dermatomyositis versus dermatomyositis with myopathy.”

The study received funding support from the Rheumatology Research Foundation and the UT Southwestern Dean’s Research Scholar program. Neither Ms. Keum nor Dr. Saardi reported having relevant disclosures.

SAN DIEGO — Women with autoimmune skin diseases are at increased risk of adverse pregnancy outcomes and may benefit from multidisciplinary care with maternal-fetal medicine specialists, results from a large case-control study suggest.

Patients with systemic autoimmune conditions are known to have an increased risk for adverse pregnancy outcomes, “but we weren’t sure if that was the case for patients with autoimmune skin conditions,” presenting study author Heejo Keum, a fourth-year medical student at the University of Texas Southwestern Medical Center, Dallas, said in an interview during a poster session at the American College of Rheumatology (ACR) 2023 annual meeting. “There are case reports or nationwide population-based studies on patients with alopecia areata and vitiligo, but those were outside of the US, so we wanted to see if these outcomes could be studied in a larger population-based study in the US.”

Doug Brunk/MDedge News

Drawing from the TriNetX US Collaborative Network, a database of electronic medical records of 94 million patients in the United States, the researchers identified pregnant patients aged 15-44 years between January 1, 2016, and December 31, 2021. Cases were defined as patients diagnosed with at least one autoimmune skin disease (ASD) prior to the end of pregnancy, including alopecia areata, bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, cutaneous lupus erythematosus, epidermolysis bullosa acquisita, morphea, pemphigus foliaceus, pemphigus vulgaris, vitiligo, and amyopathic DM. There were two control groups: healthy controls (those without ASDs, systemic lupus erythematosus or rheumatoid arthritis) and disease controls (those with SLE or RA). The researchers used ICD-10 codes to identify pregnancy endpoints, including live births, spontaneous abortion, and stillbirth. Patients with a history of hidradenitis suppurative were excluded from the analysis, as were those with common autoimmune disease such as Hashimoto’s thyroiditis, Grave’s disease, and type 1 diabetes.

The primary outcomes were adverse pregnancy outcomes defined as spontaneous abortion, gestational hypertension, preeclampsia/eclampsia, gestational diabetes, intrauterine growth restriction (IUGR), preterm premature rupture of membranes (PPROM), and preterm birth. The researchers used 1:1 propensity scoring to match patients with ASDs to controls by age, race, ethnicity, comorbidities, obesity, and substance use, and used odds ratio (OR) analysis with a 95% confidence interval (CI) to calculate each outcome.

Ms. Keum reported results from 3,654 women with ASDs, 3,654 healthy controls, 2,147 women with SLE, and 889 women with RA.

The three most common ASDs were vitiligo (30%), alopecia areata (30%), and cutaneous lupus erythematosus (27%). Compared with healthy controls, patients with ASDs were more likely to have spontaneous abortions (OR=1.5 [1.4-1.7], P<.001), and preeclampsia/eclampsia (OR=1.2 [1.0-1.3], P=.04). Compared with women with SLE, women with ASDs were less likely to have preeclampsia/eclampsia (OR=0.7 [0.6-0.9, P=.001); preterm birth (OR= 0.5 [0.4-0.7], P<.001); PPROM (OR=0.6 [0.4-0.9], P=.004), or an infant with IUGR (OR=0.6 [0.5-0.8], P<.001), but they were more likely to have a spontaneous abortion (OR=1.2 [1.1-1.3], P=.003). Overall, patients with ASDs had similar risks for adverse pregnancy outcomes as patients with RA.

“We found that patients with cutaneous lupus and vitiligo had higher rates of spontaneous abortion, which is interesting because we didn’t expect that,” Ms. Keum told this news organization. “Studies have shown that vitiligo patients might have an increased risk of pregnancy loss, so I think it’s important to have that discussion with those patients. It might benefit them to talk to a maternal-fetal medicine specialist. As for next steps, we want to look at how medication use and disease flare or disease severity play a role in APOs.”

In their poster, the researchers acknowledged limitations of the study, including the inability to verify diagnoses or assess disease severity. Also, while medication use and concomitant antiphospholipid syndrome were evaluated as risk factors for advanced pregnancy outcomes, the number of patients per group was too small for analysis.

Karl Saardi, MD, director of the inpatient dermatology service at George Washington University Hospital, Washington, who was asked to comment on the study, said that in his view, the choice of disease states included in the analysis “is a bit arbitrary.” He added that “it would have been more helpful to compare controls versus discoid lupus versus systemic lupus or controls versus amyopathic dermatomyositis versus dermatomyositis with myopathy.”

The study received funding support from the Rheumatology Research Foundation and the UT Southwestern Dean’s Research Scholar program. Neither Ms. Keum nor Dr. Saardi reported having relevant disclosures.

SAN DIEGO — Women with autoimmune skin diseases are at increased risk of adverse pregnancy outcomes and may benefit from multidisciplinary care with maternal-fetal medicine specialists, results from a large case-control study suggest.

Patients with systemic autoimmune conditions are known to have an increased risk for adverse pregnancy outcomes, “but we weren’t sure if that was the case for patients with autoimmune skin conditions,” presenting study author Heejo Keum, a fourth-year medical student at the University of Texas Southwestern Medical Center, Dallas, said in an interview during a poster session at the American College of Rheumatology (ACR) 2023 annual meeting. “There are case reports or nationwide population-based studies on patients with alopecia areata and vitiligo, but those were outside of the US, so we wanted to see if these outcomes could be studied in a larger population-based study in the US.”

Doug Brunk/MDedge News

Drawing from the TriNetX US Collaborative Network, a database of electronic medical records of 94 million patients in the United States, the researchers identified pregnant patients aged 15-44 years between January 1, 2016, and December 31, 2021. Cases were defined as patients diagnosed with at least one autoimmune skin disease (ASD) prior to the end of pregnancy, including alopecia areata, bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, cutaneous lupus erythematosus, epidermolysis bullosa acquisita, morphea, pemphigus foliaceus, pemphigus vulgaris, vitiligo, and amyopathic DM. There were two control groups: healthy controls (those without ASDs, systemic lupus erythematosus or rheumatoid arthritis) and disease controls (those with SLE or RA). The researchers used ICD-10 codes to identify pregnancy endpoints, including live births, spontaneous abortion, and stillbirth. Patients with a history of hidradenitis suppurative were excluded from the analysis, as were those with common autoimmune disease such as Hashimoto’s thyroiditis, Grave’s disease, and type 1 diabetes.

The primary outcomes were adverse pregnancy outcomes defined as spontaneous abortion, gestational hypertension, preeclampsia/eclampsia, gestational diabetes, intrauterine growth restriction (IUGR), preterm premature rupture of membranes (PPROM), and preterm birth. The researchers used 1:1 propensity scoring to match patients with ASDs to controls by age, race, ethnicity, comorbidities, obesity, and substance use, and used odds ratio (OR) analysis with a 95% confidence interval (CI) to calculate each outcome.

Ms. Keum reported results from 3,654 women with ASDs, 3,654 healthy controls, 2,147 women with SLE, and 889 women with RA.

The three most common ASDs were vitiligo (30%), alopecia areata (30%), and cutaneous lupus erythematosus (27%). Compared with healthy controls, patients with ASDs were more likely to have spontaneous abortions (OR=1.5 [1.4-1.7], P<.001), and preeclampsia/eclampsia (OR=1.2 [1.0-1.3], P=.04). Compared with women with SLE, women with ASDs were less likely to have preeclampsia/eclampsia (OR=0.7 [0.6-0.9, P=.001); preterm birth (OR= 0.5 [0.4-0.7], P<.001); PPROM (OR=0.6 [0.4-0.9], P=.004), or an infant with IUGR (OR=0.6 [0.5-0.8], P<.001), but they were more likely to have a spontaneous abortion (OR=1.2 [1.1-1.3], P=.003). Overall, patients with ASDs had similar risks for adverse pregnancy outcomes as patients with RA.

“We found that patients with cutaneous lupus and vitiligo had higher rates of spontaneous abortion, which is interesting because we didn’t expect that,” Ms. Keum told this news organization. “Studies have shown that vitiligo patients might have an increased risk of pregnancy loss, so I think it’s important to have that discussion with those patients. It might benefit them to talk to a maternal-fetal medicine specialist. As for next steps, we want to look at how medication use and disease flare or disease severity play a role in APOs.”

In their poster, the researchers acknowledged limitations of the study, including the inability to verify diagnoses or assess disease severity. Also, while medication use and concomitant antiphospholipid syndrome were evaluated as risk factors for advanced pregnancy outcomes, the number of patients per group was too small for analysis.

Karl Saardi, MD, director of the inpatient dermatology service at George Washington University Hospital, Washington, who was asked to comment on the study, said that in his view, the choice of disease states included in the analysis “is a bit arbitrary.” He added that “it would have been more helpful to compare controls versus discoid lupus versus systemic lupus or controls versus amyopathic dermatomyositis versus dermatomyositis with myopathy.”

The study received funding support from the Rheumatology Research Foundation and the UT Southwestern Dean’s Research Scholar program. Neither Ms. Keum nor Dr. Saardi reported having relevant disclosures.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.

The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.

For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.

Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.

Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).

Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.

There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.

In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.

Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”

One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”

Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.

SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.

The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.

For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.

Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.

Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).

Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.

There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.

In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.

Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”

One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”

Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.

SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.

The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.

For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.

Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.

Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).

Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.

There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.

In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.

Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”

One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”

Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.

SAN DIEGO – Treatment with benralizumab (Fasenra) achieved remission at 36 and 48 weeks at rates similar to those of mepolizumab (Nucala) in a head-to-head phase 3 trial of the two drugs for patients with a relapsing or refractory case of the rare vasculitis eosinophilic granulomatosis with polyangiitis (EGPA).

Benralizumab, a monoclonal antibody from AstraZeneca that binds to the alpha chain of the interleukin (IL)-5 receptor, is indicated as an add-on maintenance treatment for patients 12 years and older with severe eosinophilic asthma but is not currently approved for EGPA. Mepolizumab is a humanized monoclonal antibody targeting IL-5 and the only approved drug for EGPA.

Peter A. Merkel, MD, presented the trial, known as MANDARA, during a late-breaking poster session at the annual meeting of the American College of Rheumatology. A total of 140 patients with EGPA received either subcutaneous benralizumab 30 mg or mepolizumab 300 mg every 4 weeks for 52 weeks. The trial, which began recruitment in late 2019, was limited to patients at least 18 years of age with relapsing/refractory EGPA that required stable use of oral glucocorticoids (OGCs) and immunosuppressive therapy for at least 4 weeks prior to randomization, and the primary endpoint was the proportion of patients who achieved remission at weeks 36 and 48. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 plus an OGC dose of no more than 4 mg/day. Secondary endpoints included rates of accrued and maintained remission, OGC use, clinical benefit and complete response, blood eosinophil counts, total BVAS, and Vascular Damage Index scores. The mean age of the 140 patients was 52 years, and 60% were women.

Dr. Merkel and colleagues reported that the adjusted remission rate at both weeks 36 and 48 was 59.2% for those in the benralizumab arm and 56.5% for those in the mepolizumab arm (P = .7278). The percentage of patients who achieved a BVAS of 0 was similar between the two arms (83% in the benralizumab arm vs. 84.2% for those in the mepolizumab arm; P = .8502), as was the percentage of patients on an OGC dose of up to 4 mg/day (62.1% vs. 57.9%; P = .5942). At 48-52 weeks, 86.1% of patients in the benralizumab arm achieved up to a 50% reduction in OGC use, compared with 73.9% of those in the mepolizumab arm (P = .0611), and 41.4% of patients in the benralizumab arm achieved a 100% reduction in OGC use, compared with 25.8% of those in the mepolizumab arm (P = .0406).

In findings related to safety, the top three adverse events were COVID-19 (21.4% in the benralizumab arm vs. 27.1% in the mepolizumab arm, respectively), headache (17.1% vs. 15.7%), and arthralgia (17.1% vs. 11.4%).

“We were pleased with the findings because they met our expectations,” Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, said in an interview. “The hypothesis was that these two drugs would be equivalent and safe. The implication for patients is that they’ll have another treatment option for EGPA, which is an underrecognized disease with need for more effective treatments. I anticipate that the drug will be approved for use in EGPA, providing another option for treating this complicated multisystem eosinophilic-associated disease. Having more options for our biologic therapies is good.”

He characterized the retention of patients in MANDARA as “remarkable, despite the COVID-19 pandemic. Patients with rare diseases are quite dedicated to helping conduct research. They know that their disease is not common and that they could help others.”

The study was sponsored and funded by AstraZeneca. Dr. Merkel disclosed that he has received consulting fees and research support from many pharmaceutical companies, including AstraZeneca.

SAN DIEGO – Treatment with benralizumab (Fasenra) achieved remission at 36 and 48 weeks at rates similar to those of mepolizumab (Nucala) in a head-to-head phase 3 trial of the two drugs for patients with a relapsing or refractory case of the rare vasculitis eosinophilic granulomatosis with polyangiitis (EGPA).

Benralizumab, a monoclonal antibody from AstraZeneca that binds to the alpha chain of the interleukin (IL)-5 receptor, is indicated as an add-on maintenance treatment for patients 12 years and older with severe eosinophilic asthma but is not currently approved for EGPA. Mepolizumab is a humanized monoclonal antibody targeting IL-5 and the only approved drug for EGPA.

Peter A. Merkel, MD, presented the trial, known as MANDARA, during a late-breaking poster session at the annual meeting of the American College of Rheumatology. A total of 140 patients with EGPA received either subcutaneous benralizumab 30 mg or mepolizumab 300 mg every 4 weeks for 52 weeks. The trial, which began recruitment in late 2019, was limited to patients at least 18 years of age with relapsing/refractory EGPA that required stable use of oral glucocorticoids (OGCs) and immunosuppressive therapy for at least 4 weeks prior to randomization, and the primary endpoint was the proportion of patients who achieved remission at weeks 36 and 48. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 plus an OGC dose of no more than 4 mg/day. Secondary endpoints included rates of accrued and maintained remission, OGC use, clinical benefit and complete response, blood eosinophil counts, total BVAS, and Vascular Damage Index scores. The mean age of the 140 patients was 52 years, and 60% were women.

Dr. Merkel and colleagues reported that the adjusted remission rate at both weeks 36 and 48 was 59.2% for those in the benralizumab arm and 56.5% for those in the mepolizumab arm (P = .7278). The percentage of patients who achieved a BVAS of 0 was similar between the two arms (83% in the benralizumab arm vs. 84.2% for those in the mepolizumab arm; P = .8502), as was the percentage of patients on an OGC dose of up to 4 mg/day (62.1% vs. 57.9%; P = .5942). At 48-52 weeks, 86.1% of patients in the benralizumab arm achieved up to a 50% reduction in OGC use, compared with 73.9% of those in the mepolizumab arm (P = .0611), and 41.4% of patients in the benralizumab arm achieved a 100% reduction in OGC use, compared with 25.8% of those in the mepolizumab arm (P = .0406).

In findings related to safety, the top three adverse events were COVID-19 (21.4% in the benralizumab arm vs. 27.1% in the mepolizumab arm, respectively), headache (17.1% vs. 15.7%), and arthralgia (17.1% vs. 11.4%).

“We were pleased with the findings because they met our expectations,” Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, said in an interview. “The hypothesis was that these two drugs would be equivalent and safe. The implication for patients is that they’ll have another treatment option for EGPA, which is an underrecognized disease with need for more effective treatments. I anticipate that the drug will be approved for use in EGPA, providing another option for treating this complicated multisystem eosinophilic-associated disease. Having more options for our biologic therapies is good.”

He characterized the retention of patients in MANDARA as “remarkable, despite the COVID-19 pandemic. Patients with rare diseases are quite dedicated to helping conduct research. They know that their disease is not common and that they could help others.”

The study was sponsored and funded by AstraZeneca. Dr. Merkel disclosed that he has received consulting fees and research support from many pharmaceutical companies, including AstraZeneca.

SAN DIEGO – Treatment with benralizumab (Fasenra) achieved remission at 36 and 48 weeks at rates similar to those of mepolizumab (Nucala) in a head-to-head phase 3 trial of the two drugs for patients with a relapsing or refractory case of the rare vasculitis eosinophilic granulomatosis with polyangiitis (EGPA).

Benralizumab, a monoclonal antibody from AstraZeneca that binds to the alpha chain of the interleukin (IL)-5 receptor, is indicated as an add-on maintenance treatment for patients 12 years and older with severe eosinophilic asthma but is not currently approved for EGPA. Mepolizumab is a humanized monoclonal antibody targeting IL-5 and the only approved drug for EGPA.

Peter A. Merkel, MD, presented the trial, known as MANDARA, during a late-breaking poster session at the annual meeting of the American College of Rheumatology. A total of 140 patients with EGPA received either subcutaneous benralizumab 30 mg or mepolizumab 300 mg every 4 weeks for 52 weeks. The trial, which began recruitment in late 2019, was limited to patients at least 18 years of age with relapsing/refractory EGPA that required stable use of oral glucocorticoids (OGCs) and immunosuppressive therapy for at least 4 weeks prior to randomization, and the primary endpoint was the proportion of patients who achieved remission at weeks 36 and 48. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 plus an OGC dose of no more than 4 mg/day. Secondary endpoints included rates of accrued and maintained remission, OGC use, clinical benefit and complete response, blood eosinophil counts, total BVAS, and Vascular Damage Index scores. The mean age of the 140 patients was 52 years, and 60% were women.

Dr. Merkel and colleagues reported that the adjusted remission rate at both weeks 36 and 48 was 59.2% for those in the benralizumab arm and 56.5% for those in the mepolizumab arm (P = .7278). The percentage of patients who achieved a BVAS of 0 was similar between the two arms (83% in the benralizumab arm vs. 84.2% for those in the mepolizumab arm; P = .8502), as was the percentage of patients on an OGC dose of up to 4 mg/day (62.1% vs. 57.9%; P = .5942). At 48-52 weeks, 86.1% of patients in the benralizumab arm achieved up to a 50% reduction in OGC use, compared with 73.9% of those in the mepolizumab arm (P = .0611), and 41.4% of patients in the benralizumab arm achieved a 100% reduction in OGC use, compared with 25.8% of those in the mepolizumab arm (P = .0406).

In findings related to safety, the top three adverse events were COVID-19 (21.4% in the benralizumab arm vs. 27.1% in the mepolizumab arm, respectively), headache (17.1% vs. 15.7%), and arthralgia (17.1% vs. 11.4%).

“We were pleased with the findings because they met our expectations,” Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, said in an interview. “The hypothesis was that these two drugs would be equivalent and safe. The implication for patients is that they’ll have another treatment option for EGPA, which is an underrecognized disease with need for more effective treatments. I anticipate that the drug will be approved for use in EGPA, providing another option for treating this complicated multisystem eosinophilic-associated disease. Having more options for our biologic therapies is good.”

He characterized the retention of patients in MANDARA as “remarkable, despite the COVID-19 pandemic. Patients with rare diseases are quite dedicated to helping conduct research. They know that their disease is not common and that they could help others.”

The study was sponsored and funded by AstraZeneca. Dr. Merkel disclosed that he has received consulting fees and research support from many pharmaceutical companies, including AstraZeneca.