Dermatology News

Racial disparities in melanoma stage at diagnosis were less pronounced in a large cohort of Veterans Affairs patients, compared with a large cohort of U.S. men, a new analysis shows.

“The trend of a lower racial disparity in the VA in the proportion of melanomas with local disease and in the proportion of distant metastasis at presentation was observed across age groups,” wrote Martin A. Weinstock MD, PhD, and Rachel K. Lim, of the department of dermatology at Brown University, Providence, R.I., and the Center for Dermatoepidemiology at the VA Providence Healthcare System. The study was published online in the Journal of the American Academy of Dermatology.

“Melanoma was the fourth-most common cancer [diagnosed] in male VA patients in 2010,” wrote the authors, who also pointed out that “prior surveys found that 11%-13% of U.S. active-duty personnel routinely use sunscreen despite significant occupational sun exposure. Racial disparities are important concerns in the VA and elsewhere.”

To compare the stage of melanoma at presentation among White and non-Whites patients in the VA and in the general U.S. population, the researchers identified invasive cutaneous melanoma cases from 2000 to 2019 in the VA Corporate Data Warehouse and the Surveillance, Epidemiology and End Results Program (SEER).

They restricted the analysis to men because of the small proportion of women in the at-risk veteran population and excluded cases with an age younger than 20, those with unknown histology, and melanoma in situ. The researchers performed two-tailed z-tests to evaluate the difference in proportions of melanoma stages between the veteran population and the general population.

The analysis included 44,077 cases of invasive melanoma in the VA and 217,030 in SEER. Racial disparities in melanoma staging were substantially less pronounced in the VA than in SEER.

In the VA, localized disease represented 77.9% of melanomas among Whites versus 71.0% among non-Whites. But in SEER, localized disease represented 80.7% of melanomas among Whites versus 61.5% in non-Whites – over double the VA disparity (P < .0001).

Christoph Burgstedt/Science Photo Library/Getty Images

Likewise, the disparity between Whites and nonwhites observed for regional or distant metastatic disease at presentation in the VA was lower than the disparity observed in SEER. For example, in the VA, distant metastatic disease at presentation represented 6.1% of melanomas among Whites versus 8.6% among non-Whites, while in SEER it represented 4.8% of melanomas among Whites versus 11.3% in non-Whites – again, more than double the VA disparity (P < .0001).

“These differences between the VA and SEER were less marked” among those older than 65 years, the researchers wrote. “Notably, the differences between VA and SEER in racial disparities among those greater than 65 in age were still significant for localized disease and for distant metastasis.”

The findings suggest that the VA “may be more effective in reducing racial disparities in melanoma stage at diagnosis, potentially due to all patients in the VA dataset having insured access to health care, regardless of socioeconomic status,” the researchers concluded. Similarly, the decreased difference in racial disparities observed in patients older than 65 across systems “may be related to the availability of Medicare to the older general populations. The authors acknowledged several study limitations, such as the predominantly elderly and male VA population, potentially underreported utilization of non-VA dermatologic care, and variation in geographic regions covered by each database.

Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, who was asked to comment on the work, said in an interview he would have liked to see a more detailed breakdown of the younger patients, “for those in their 30s and 40s, to see if this trend held up.”

He would have also liked to see how the data trended over time, adding, “while this, broadly, may be good news for our veterans, attributing this finding to a reduction in access disparity or some other organizational intervention seems a little premature. Regardless, Dr. Weinstock has given us, once again, information from our veterans to probe for the betterment of all patients.”

The researchers reported having no relevant disclosures and the study had no funding. Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.

Racial disparities in melanoma stage at diagnosis were less pronounced in a large cohort of Veterans Affairs patients, compared with a large cohort of U.S. men, a new analysis shows.

“The trend of a lower racial disparity in the VA in the proportion of melanomas with local disease and in the proportion of distant metastasis at presentation was observed across age groups,” wrote Martin A. Weinstock MD, PhD, and Rachel K. Lim, of the department of dermatology at Brown University, Providence, R.I., and the Center for Dermatoepidemiology at the VA Providence Healthcare System. The study was published online in the Journal of the American Academy of Dermatology.

“Melanoma was the fourth-most common cancer [diagnosed] in male VA patients in 2010,” wrote the authors, who also pointed out that “prior surveys found that 11%-13% of U.S. active-duty personnel routinely use sunscreen despite significant occupational sun exposure. Racial disparities are important concerns in the VA and elsewhere.”

To compare the stage of melanoma at presentation among White and non-Whites patients in the VA and in the general U.S. population, the researchers identified invasive cutaneous melanoma cases from 2000 to 2019 in the VA Corporate Data Warehouse and the Surveillance, Epidemiology and End Results Program (SEER).

They restricted the analysis to men because of the small proportion of women in the at-risk veteran population and excluded cases with an age younger than 20, those with unknown histology, and melanoma in situ. The researchers performed two-tailed z-tests to evaluate the difference in proportions of melanoma stages between the veteran population and the general population.

The analysis included 44,077 cases of invasive melanoma in the VA and 217,030 in SEER. Racial disparities in melanoma staging were substantially less pronounced in the VA than in SEER.

In the VA, localized disease represented 77.9% of melanomas among Whites versus 71.0% among non-Whites. But in SEER, localized disease represented 80.7% of melanomas among Whites versus 61.5% in non-Whites – over double the VA disparity (P < .0001).

Christoph Burgstedt/Science Photo Library/Getty Images

Likewise, the disparity between Whites and nonwhites observed for regional or distant metastatic disease at presentation in the VA was lower than the disparity observed in SEER. For example, in the VA, distant metastatic disease at presentation represented 6.1% of melanomas among Whites versus 8.6% among non-Whites, while in SEER it represented 4.8% of melanomas among Whites versus 11.3% in non-Whites – again, more than double the VA disparity (P < .0001).

“These differences between the VA and SEER were less marked” among those older than 65 years, the researchers wrote. “Notably, the differences between VA and SEER in racial disparities among those greater than 65 in age were still significant for localized disease and for distant metastasis.”

The findings suggest that the VA “may be more effective in reducing racial disparities in melanoma stage at diagnosis, potentially due to all patients in the VA dataset having insured access to health care, regardless of socioeconomic status,” the researchers concluded. Similarly, the decreased difference in racial disparities observed in patients older than 65 across systems “may be related to the availability of Medicare to the older general populations. The authors acknowledged several study limitations, such as the predominantly elderly and male VA population, potentially underreported utilization of non-VA dermatologic care, and variation in geographic regions covered by each database.

Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, who was asked to comment on the work, said in an interview he would have liked to see a more detailed breakdown of the younger patients, “for those in their 30s and 40s, to see if this trend held up.”

He would have also liked to see how the data trended over time, adding, “while this, broadly, may be good news for our veterans, attributing this finding to a reduction in access disparity or some other organizational intervention seems a little premature. Regardless, Dr. Weinstock has given us, once again, information from our veterans to probe for the betterment of all patients.”

The researchers reported having no relevant disclosures and the study had no funding. Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.

Racial disparities in melanoma stage at diagnosis were less pronounced in a large cohort of Veterans Affairs patients, compared with a large cohort of U.S. men, a new analysis shows.

“The trend of a lower racial disparity in the VA in the proportion of melanomas with local disease and in the proportion of distant metastasis at presentation was observed across age groups,” wrote Martin A. Weinstock MD, PhD, and Rachel K. Lim, of the department of dermatology at Brown University, Providence, R.I., and the Center for Dermatoepidemiology at the VA Providence Healthcare System. The study was published online in the Journal of the American Academy of Dermatology.

“Melanoma was the fourth-most common cancer [diagnosed] in male VA patients in 2010,” wrote the authors, who also pointed out that “prior surveys found that 11%-13% of U.S. active-duty personnel routinely use sunscreen despite significant occupational sun exposure. Racial disparities are important concerns in the VA and elsewhere.”

To compare the stage of melanoma at presentation among White and non-Whites patients in the VA and in the general U.S. population, the researchers identified invasive cutaneous melanoma cases from 2000 to 2019 in the VA Corporate Data Warehouse and the Surveillance, Epidemiology and End Results Program (SEER).

They restricted the analysis to men because of the small proportion of women in the at-risk veteran population and excluded cases with an age younger than 20, those with unknown histology, and melanoma in situ. The researchers performed two-tailed z-tests to evaluate the difference in proportions of melanoma stages between the veteran population and the general population.

The analysis included 44,077 cases of invasive melanoma in the VA and 217,030 in SEER. Racial disparities in melanoma staging were substantially less pronounced in the VA than in SEER.

In the VA, localized disease represented 77.9% of melanomas among Whites versus 71.0% among non-Whites. But in SEER, localized disease represented 80.7% of melanomas among Whites versus 61.5% in non-Whites – over double the VA disparity (P < .0001).

Christoph Burgstedt/Science Photo Library/Getty Images

Likewise, the disparity between Whites and nonwhites observed for regional or distant metastatic disease at presentation in the VA was lower than the disparity observed in SEER. For example, in the VA, distant metastatic disease at presentation represented 6.1% of melanomas among Whites versus 8.6% among non-Whites, while in SEER it represented 4.8% of melanomas among Whites versus 11.3% in non-Whites – again, more than double the VA disparity (P < .0001).

“These differences between the VA and SEER were less marked” among those older than 65 years, the researchers wrote. “Notably, the differences between VA and SEER in racial disparities among those greater than 65 in age were still significant for localized disease and for distant metastasis.”

The findings suggest that the VA “may be more effective in reducing racial disparities in melanoma stage at diagnosis, potentially due to all patients in the VA dataset having insured access to health care, regardless of socioeconomic status,” the researchers concluded. Similarly, the decreased difference in racial disparities observed in patients older than 65 across systems “may be related to the availability of Medicare to the older general populations. The authors acknowledged several study limitations, such as the predominantly elderly and male VA population, potentially underreported utilization of non-VA dermatologic care, and variation in geographic regions covered by each database.

Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, who was asked to comment on the work, said in an interview he would have liked to see a more detailed breakdown of the younger patients, “for those in their 30s and 40s, to see if this trend held up.”

He would have also liked to see how the data trended over time, adding, “while this, broadly, may be good news for our veterans, attributing this finding to a reduction in access disparity or some other organizational intervention seems a little premature. Regardless, Dr. Weinstock has given us, once again, information from our veterans to probe for the betterment of all patients.”

The researchers reported having no relevant disclosures and the study had no funding. Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.

WASHINGTON – A substantial proportion of adults with moderate to severe atopic dermatitis (AD) treated with oral abrocitinib 100 mg or 200 mg once daily for up to 96 weeks had sustained improvements in skin clearance, itch, and quality of life in a post hoc analysis of the JADE EXTEND phase 3 trial, Andrew F. Alexis, MD, MPH, reported in a late-breaker abstract session at the annual Revolutionizing Atopic Dermatitis conference.

The analysis stratified patients by age – 18-50 and over 50 years – and found that the sustained improvement with the JAK-1 selective inhibitor as monotherapy was seen regardless of age. “In practice, patients who are older tend to have had AD for a longer period of time and tend to be more difficult to treat so it’s reassuring to see that even in the over-50 age group, they show substantial responses, even with more stringent endpoints,” said Dr. Alexis, professor of clinical dermatology at Weill Cornell Medical College, New York.

At week 96, for instance, the proportion of patients who achieved at least a 75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) was 73% with the 100-mg dose and 85% with the 200-mg dose in the younger age group, and 86% and 89%, respectively, in the older age group.

An EASI-90 response – one of the more stringent outcomes – was achieved by 45% and 58% in the 18-50 group and 58% and 73% in the over 50 group (for 100-mg and 200-mg doses, respectively), Dr. Alexis reported.

The interim analysis also showed dose-dependent efficacy overall up to 96 weeks in the younger age group but only up to 48 weeks in the older age group. Response to some outcome measures in patients over age 50 years was “less clearly dose dependent after week 48” than earlier, Dr. Alexis said.

The ongoing JADE EXTEND trial enrolled patients who had participated in the phase 3 JADE clinical trials. This analysis covered 1,309 patients who were enrolled by a September 2021 cutoff. The patient population leaned young: Eighty percent (1,046) were aged 18-50, and 20% (263) were over 50.

Patients who were randomly assigned to abrocitinib 200 mg or 100 mg in the parent trials continued to receive the same dose in JADE EXTEND with blinding maintained. Those who received placebo in the qualifying trial were randomly assigned to abrocitinib 200 mg or 100 mg. And patients from JADE DARE continued with their dosing of 200 mg. Grouping by age for the analysis was made based on the age recorded at the screening visit of the qualifying trial.
 

IGA, PP-NRS, and DLQI results

At week 96, the proportion of patients 18-50 years of age who achieved the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline was 44% in the 100-mg group and 55% in the 200-mg group. Among patients over 50, these proportions were 51% and 58%, respectively.

The proportion of patients who achieved at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS) score was 54% and 66% (on 100 mg and 200 mg, respectively) among those aged 18-50, and 79% and 80%, respectively, among those over 50.

Looking at more stringent outcomes, 26% and 38% in the 18-50 group on 100 mg and 200 mg, respectively, achieved a PP-NRS of 0/1, as did 54% and 44% in the over-50 group.

Lastly, a score of less than 2 on the Dermatology Life Quality Index (DLQI 0/1) was achieved by 32% and 41% of patients aged 18-50 and by 51% and 48% of patients over 50, for the 100-mg and 200-mg doses, respectively.

The decline in dose-dependent efficacy in the older age group after 48 weeks may be due to the smaller sample of older patients and/or the fact that a higher proportion of older patients had moderate baseline disease per their IGA score, versus severe disease, compared with the younger patients, Dr. Alexis said. “We see a skewing toward a bit more severe [disease] in the younger age group compared to the older,” he noted.

Abrocitinib (Cibinqo) is approved for the treatment of moderate to severe AD in adolescents aged 12 and up and adults whose disease is not adequately controlled with other systemic treatments or those for whom the use of these drugs is not advised. It is available in a 50-mg dose for dose adjustments in special populations, but this dose was not studied in the clinical trials, Dr. Alexis noted. The interim analysis did not include safety data.

In a separate presentation in which he reviewed long-term data on AD medications, Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, said that most patients who meet defined endpoints at week 12 of treatment with abrocitinib maintain that response over time. “By and large, there’s a steep initial rise that flattens over the long run, which is what you want to see. People getting that response are generally staying there over the course of treatment,” he said, referring to the JADE EXTEND data up to week 48.

It’s important to also appreciate, however, that the proportion of patients meeting efficacy outcomes in the trials of abrocitinib has grown well beyond 12 weeks, Dr. Chovatiya said.

Pointing to data presented at a 2021 RAD meeting depicting the proportion of 12-week nonresponders achieving a response at weeks 24 and 48 on IGA 0/1, EASI-75, and PP-NRS, Dr. Chovatiya said the level of response grew at both time points. “You’re capturing a chunk of people well beyond the primary endpoint if you keep them on therapy continuously, suggesting that ... we may need to reframe how we’re thinking about oral JAK inhibitors,” he said. “Not only are they rapidly acting, but they are medications that can provide good control and changes in the long run.”

Dr. Alexis and Dr. Chovatiya disclosed ties with Pfizer, which funded the study.

WASHINGTON – A substantial proportion of adults with moderate to severe atopic dermatitis (AD) treated with oral abrocitinib 100 mg or 200 mg once daily for up to 96 weeks had sustained improvements in skin clearance, itch, and quality of life in a post hoc analysis of the JADE EXTEND phase 3 trial, Andrew F. Alexis, MD, MPH, reported in a late-breaker abstract session at the annual Revolutionizing Atopic Dermatitis conference.

The analysis stratified patients by age – 18-50 and over 50 years – and found that the sustained improvement with the JAK-1 selective inhibitor as monotherapy was seen regardless of age. “In practice, patients who are older tend to have had AD for a longer period of time and tend to be more difficult to treat so it’s reassuring to see that even in the over-50 age group, they show substantial responses, even with more stringent endpoints,” said Dr. Alexis, professor of clinical dermatology at Weill Cornell Medical College, New York.

At week 96, for instance, the proportion of patients who achieved at least a 75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) was 73% with the 100-mg dose and 85% with the 200-mg dose in the younger age group, and 86% and 89%, respectively, in the older age group.

An EASI-90 response – one of the more stringent outcomes – was achieved by 45% and 58% in the 18-50 group and 58% and 73% in the over 50 group (for 100-mg and 200-mg doses, respectively), Dr. Alexis reported.

The interim analysis also showed dose-dependent efficacy overall up to 96 weeks in the younger age group but only up to 48 weeks in the older age group. Response to some outcome measures in patients over age 50 years was “less clearly dose dependent after week 48” than earlier, Dr. Alexis said.

The ongoing JADE EXTEND trial enrolled patients who had participated in the phase 3 JADE clinical trials. This analysis covered 1,309 patients who were enrolled by a September 2021 cutoff. The patient population leaned young: Eighty percent (1,046) were aged 18-50, and 20% (263) were over 50.

Patients who were randomly assigned to abrocitinib 200 mg or 100 mg in the parent trials continued to receive the same dose in JADE EXTEND with blinding maintained. Those who received placebo in the qualifying trial were randomly assigned to abrocitinib 200 mg or 100 mg. And patients from JADE DARE continued with their dosing of 200 mg. Grouping by age for the analysis was made based on the age recorded at the screening visit of the qualifying trial.
 

IGA, PP-NRS, and DLQI results

At week 96, the proportion of patients 18-50 years of age who achieved the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline was 44% in the 100-mg group and 55% in the 200-mg group. Among patients over 50, these proportions were 51% and 58%, respectively.

The proportion of patients who achieved at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS) score was 54% and 66% (on 100 mg and 200 mg, respectively) among those aged 18-50, and 79% and 80%, respectively, among those over 50.

Looking at more stringent outcomes, 26% and 38% in the 18-50 group on 100 mg and 200 mg, respectively, achieved a PP-NRS of 0/1, as did 54% and 44% in the over-50 group.

Lastly, a score of less than 2 on the Dermatology Life Quality Index (DLQI 0/1) was achieved by 32% and 41% of patients aged 18-50 and by 51% and 48% of patients over 50, for the 100-mg and 200-mg doses, respectively.

The decline in dose-dependent efficacy in the older age group after 48 weeks may be due to the smaller sample of older patients and/or the fact that a higher proportion of older patients had moderate baseline disease per their IGA score, versus severe disease, compared with the younger patients, Dr. Alexis said. “We see a skewing toward a bit more severe [disease] in the younger age group compared to the older,” he noted.

Abrocitinib (Cibinqo) is approved for the treatment of moderate to severe AD in adolescents aged 12 and up and adults whose disease is not adequately controlled with other systemic treatments or those for whom the use of these drugs is not advised. It is available in a 50-mg dose for dose adjustments in special populations, but this dose was not studied in the clinical trials, Dr. Alexis noted. The interim analysis did not include safety data.

In a separate presentation in which he reviewed long-term data on AD medications, Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, said that most patients who meet defined endpoints at week 12 of treatment with abrocitinib maintain that response over time. “By and large, there’s a steep initial rise that flattens over the long run, which is what you want to see. People getting that response are generally staying there over the course of treatment,” he said, referring to the JADE EXTEND data up to week 48.

It’s important to also appreciate, however, that the proportion of patients meeting efficacy outcomes in the trials of abrocitinib has grown well beyond 12 weeks, Dr. Chovatiya said.

Pointing to data presented at a 2021 RAD meeting depicting the proportion of 12-week nonresponders achieving a response at weeks 24 and 48 on IGA 0/1, EASI-75, and PP-NRS, Dr. Chovatiya said the level of response grew at both time points. “You’re capturing a chunk of people well beyond the primary endpoint if you keep them on therapy continuously, suggesting that ... we may need to reframe how we’re thinking about oral JAK inhibitors,” he said. “Not only are they rapidly acting, but they are medications that can provide good control and changes in the long run.”

Dr. Alexis and Dr. Chovatiya disclosed ties with Pfizer, which funded the study.

WASHINGTON – A substantial proportion of adults with moderate to severe atopic dermatitis (AD) treated with oral abrocitinib 100 mg or 200 mg once daily for up to 96 weeks had sustained improvements in skin clearance, itch, and quality of life in a post hoc analysis of the JADE EXTEND phase 3 trial, Andrew F. Alexis, MD, MPH, reported in a late-breaker abstract session at the annual Revolutionizing Atopic Dermatitis conference.

The analysis stratified patients by age – 18-50 and over 50 years – and found that the sustained improvement with the JAK-1 selective inhibitor as monotherapy was seen regardless of age. “In practice, patients who are older tend to have had AD for a longer period of time and tend to be more difficult to treat so it’s reassuring to see that even in the over-50 age group, they show substantial responses, even with more stringent endpoints,” said Dr. Alexis, professor of clinical dermatology at Weill Cornell Medical College, New York.

At week 96, for instance, the proportion of patients who achieved at least a 75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) was 73% with the 100-mg dose and 85% with the 200-mg dose in the younger age group, and 86% and 89%, respectively, in the older age group.

An EASI-90 response – one of the more stringent outcomes – was achieved by 45% and 58% in the 18-50 group and 58% and 73% in the over 50 group (for 100-mg and 200-mg doses, respectively), Dr. Alexis reported.

The interim analysis also showed dose-dependent efficacy overall up to 96 weeks in the younger age group but only up to 48 weeks in the older age group. Response to some outcome measures in patients over age 50 years was “less clearly dose dependent after week 48” than earlier, Dr. Alexis said.

The ongoing JADE EXTEND trial enrolled patients who had participated in the phase 3 JADE clinical trials. This analysis covered 1,309 patients who were enrolled by a September 2021 cutoff. The patient population leaned young: Eighty percent (1,046) were aged 18-50, and 20% (263) were over 50.

Patients who were randomly assigned to abrocitinib 200 mg or 100 mg in the parent trials continued to receive the same dose in JADE EXTEND with blinding maintained. Those who received placebo in the qualifying trial were randomly assigned to abrocitinib 200 mg or 100 mg. And patients from JADE DARE continued with their dosing of 200 mg. Grouping by age for the analysis was made based on the age recorded at the screening visit of the qualifying trial.
 

IGA, PP-NRS, and DLQI results

At week 96, the proportion of patients 18-50 years of age who achieved the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline was 44% in the 100-mg group and 55% in the 200-mg group. Among patients over 50, these proportions were 51% and 58%, respectively.

The proportion of patients who achieved at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS) score was 54% and 66% (on 100 mg and 200 mg, respectively) among those aged 18-50, and 79% and 80%, respectively, among those over 50.

Looking at more stringent outcomes, 26% and 38% in the 18-50 group on 100 mg and 200 mg, respectively, achieved a PP-NRS of 0/1, as did 54% and 44% in the over-50 group.

Lastly, a score of less than 2 on the Dermatology Life Quality Index (DLQI 0/1) was achieved by 32% and 41% of patients aged 18-50 and by 51% and 48% of patients over 50, for the 100-mg and 200-mg doses, respectively.

The decline in dose-dependent efficacy in the older age group after 48 weeks may be due to the smaller sample of older patients and/or the fact that a higher proportion of older patients had moderate baseline disease per their IGA score, versus severe disease, compared with the younger patients, Dr. Alexis said. “We see a skewing toward a bit more severe [disease] in the younger age group compared to the older,” he noted.

Abrocitinib (Cibinqo) is approved for the treatment of moderate to severe AD in adolescents aged 12 and up and adults whose disease is not adequately controlled with other systemic treatments or those for whom the use of these drugs is not advised. It is available in a 50-mg dose for dose adjustments in special populations, but this dose was not studied in the clinical trials, Dr. Alexis noted. The interim analysis did not include safety data.

In a separate presentation in which he reviewed long-term data on AD medications, Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, said that most patients who meet defined endpoints at week 12 of treatment with abrocitinib maintain that response over time. “By and large, there’s a steep initial rise that flattens over the long run, which is what you want to see. People getting that response are generally staying there over the course of treatment,” he said, referring to the JADE EXTEND data up to week 48.

It’s important to also appreciate, however, that the proportion of patients meeting efficacy outcomes in the trials of abrocitinib has grown well beyond 12 weeks, Dr. Chovatiya said.

Pointing to data presented at a 2021 RAD meeting depicting the proportion of 12-week nonresponders achieving a response at weeks 24 and 48 on IGA 0/1, EASI-75, and PP-NRS, Dr. Chovatiya said the level of response grew at both time points. “You’re capturing a chunk of people well beyond the primary endpoint if you keep them on therapy continuously, suggesting that ... we may need to reframe how we’re thinking about oral JAK inhibitors,” he said. “Not only are they rapidly acting, but they are medications that can provide good control and changes in the long run.”

Dr. Alexis and Dr. Chovatiya disclosed ties with Pfizer, which funded the study.

The European Commission has approved secukinumab (Cosentyx) as a treatment for adults with active, moderate to severe hidradenitis suppurativa (HS) that didn’t respond to conventional therapy.

The biologic is the first interleukin-17A (IL-17A) inhibitor to be approved for the treatment of moderate to severe HS. The manufacturer, Novartis, expects a regulatory decision from the U.S. Food and Drug Administration later this year, according to a company press release announcing the approval.

The European approval is based on the results from the phase 3 SUNSHINE and SUNRISE trials, which evaluated the efficacy, safety, and tolerability of the drug. The multicenter, randomized, placebo-controlled, double-blind trials enrolled a total of more than 1,000 adults with moderate to severe HS.

Patients were randomly assigned either to receive subcutaneous secukinumab 300 mg every 2 weeks or 4 weeks or to receive placebo. The treatment was effective at improving the symptoms of HS when given every 2 weeks, according to results recently published in The Lancet.

The primary outcome measure for both trials was HS clinical response – defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or draining fistulae, compared with baseline.

In the studies, 42% and 45% of patients treated with secukinumab every 2 weeks in the SUNRISE and SUNSHINE trials, respectively, had a clinical response at 16 weeks, compared with 31% and 34% among those who received placebo, which were statistically significant differences. A significant clinical response was seen at week 4 in the SUNSHINE trial and in week 2 in the SUNRISE trial. In both trials, clinical efficacy was sustained to the end of the trial, at week 52.

Headaches were the most common side effect. They affected approximately 1 in 10 patients in both trials.

HS, also called acne inversa, is a chronic skin condition that causes painful lesions. The condition affects 1%- 2% of the U.S. population, according to the nonprofit Hidradenitis Suppurativa Foundation. It also disproportionately affects young adults, women, and Black patients.

In Europe, about 200,000 people live with moderate to severe stages of the condition, according to the Novartis press release.

Secukinumab inhibits IL-17A, a cytokine involved in the inflammation of psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and nonradiographic axial spondylarthritis. It has been approved for the treatment of those conditions, as well as for the treatment of juvenile idiopathic arthritis and enthesitis-related arthritis in the United States and the European Union.

The only other approved biologic therapy for HS is the tumor necrosis factor inhibitor adalimumab.

Novartis is investigating the potential application of secukinumab for the treatment of lupus nephritis and giant cell arteritis, as well as polymyalgia rheumatica and rotator cuff tendinopathy, according to the company press release.

The study published in The Lancet was funded by Novartis.

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

The European Commission has approved secukinumab (Cosentyx) as a treatment for adults with active, moderate to severe hidradenitis suppurativa (HS) that didn’t respond to conventional therapy.

The biologic is the first interleukin-17A (IL-17A) inhibitor to be approved for the treatment of moderate to severe HS. The manufacturer, Novartis, expects a regulatory decision from the U.S. Food and Drug Administration later this year, according to a company press release announcing the approval.

The European approval is based on the results from the phase 3 SUNSHINE and SUNRISE trials, which evaluated the efficacy, safety, and tolerability of the drug. The multicenter, randomized, placebo-controlled, double-blind trials enrolled a total of more than 1,000 adults with moderate to severe HS.

Patients were randomly assigned either to receive subcutaneous secukinumab 300 mg every 2 weeks or 4 weeks or to receive placebo. The treatment was effective at improving the symptoms of HS when given every 2 weeks, according to results recently published in The Lancet.

The primary outcome measure for both trials was HS clinical response – defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or draining fistulae, compared with baseline.

In the studies, 42% and 45% of patients treated with secukinumab every 2 weeks in the SUNRISE and SUNSHINE trials, respectively, had a clinical response at 16 weeks, compared with 31% and 34% among those who received placebo, which were statistically significant differences. A significant clinical response was seen at week 4 in the SUNSHINE trial and in week 2 in the SUNRISE trial. In both trials, clinical efficacy was sustained to the end of the trial, at week 52.

Headaches were the most common side effect. They affected approximately 1 in 10 patients in both trials.

HS, also called acne inversa, is a chronic skin condition that causes painful lesions. The condition affects 1%- 2% of the U.S. population, according to the nonprofit Hidradenitis Suppurativa Foundation. It also disproportionately affects young adults, women, and Black patients.

In Europe, about 200,000 people live with moderate to severe stages of the condition, according to the Novartis press release.

Secukinumab inhibits IL-17A, a cytokine involved in the inflammation of psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and nonradiographic axial spondylarthritis. It has been approved for the treatment of those conditions, as well as for the treatment of juvenile idiopathic arthritis and enthesitis-related arthritis in the United States and the European Union.

The only other approved biologic therapy for HS is the tumor necrosis factor inhibitor adalimumab.

Novartis is investigating the potential application of secukinumab for the treatment of lupus nephritis and giant cell arteritis, as well as polymyalgia rheumatica and rotator cuff tendinopathy, according to the company press release.

The study published in The Lancet was funded by Novartis.

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

The European Commission has approved secukinumab (Cosentyx) as a treatment for adults with active, moderate to severe hidradenitis suppurativa (HS) that didn’t respond to conventional therapy.

The biologic is the first interleukin-17A (IL-17A) inhibitor to be approved for the treatment of moderate to severe HS. The manufacturer, Novartis, expects a regulatory decision from the U.S. Food and Drug Administration later this year, according to a company press release announcing the approval.

The European approval is based on the results from the phase 3 SUNSHINE and SUNRISE trials, which evaluated the efficacy, safety, and tolerability of the drug. The multicenter, randomized, placebo-controlled, double-blind trials enrolled a total of more than 1,000 adults with moderate to severe HS.

Patients were randomly assigned either to receive subcutaneous secukinumab 300 mg every 2 weeks or 4 weeks or to receive placebo. The treatment was effective at improving the symptoms of HS when given every 2 weeks, according to results recently published in The Lancet.

The primary outcome measure for both trials was HS clinical response – defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or draining fistulae, compared with baseline.

In the studies, 42% and 45% of patients treated with secukinumab every 2 weeks in the SUNRISE and SUNSHINE trials, respectively, had a clinical response at 16 weeks, compared with 31% and 34% among those who received placebo, which were statistically significant differences. A significant clinical response was seen at week 4 in the SUNSHINE trial and in week 2 in the SUNRISE trial. In both trials, clinical efficacy was sustained to the end of the trial, at week 52.

Headaches were the most common side effect. They affected approximately 1 in 10 patients in both trials.

HS, also called acne inversa, is a chronic skin condition that causes painful lesions. The condition affects 1%- 2% of the U.S. population, according to the nonprofit Hidradenitis Suppurativa Foundation. It also disproportionately affects young adults, women, and Black patients.

In Europe, about 200,000 people live with moderate to severe stages of the condition, according to the Novartis press release.

Secukinumab inhibits IL-17A, a cytokine involved in the inflammation of psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and nonradiographic axial spondylarthritis. It has been approved for the treatment of those conditions, as well as for the treatment of juvenile idiopathic arthritis and enthesitis-related arthritis in the United States and the European Union.

The only other approved biologic therapy for HS is the tumor necrosis factor inhibitor adalimumab.

Novartis is investigating the potential application of secukinumab for the treatment of lupus nephritis and giant cell arteritis, as well as polymyalgia rheumatica and rotator cuff tendinopathy, according to the company press release.

The study published in The Lancet was funded by Novartis.

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

WASHINGTON – The LIBERTY AD open-label extension study of dupilumab is closing after 5 years with the small number of remaining patients showing stable and sustained improvements in skin lesions and pruritus and no new emergent side effects, Lisa Beck, MD, reported during a late-breaking session at the annual Revolutionizing Atopic Dermatitis conference.

Other recent research on the biologic has shown that it improves lesional skin barrier function and rapidly reduces the abundance of Staphylococcus aureus on lesional skin, Dr. Beck, professor of dermatology at the University of Rochester (N.Y.), said during another session at the meeting on long-term control of AD. Dr. Beck directs a laboratory at the University of Rochester Medical Center that focuses on understanding AD and is involved in the National Institute of Allergy and Infectious Diseases (NIAID)-funded Atopic Dermatitis Research Network (ADRN).

The LIBERTY AD open-label extension (OLE) study was a phase 3 trial of 2,677 adults with moderate to severe AD who had participated in previous dupilumab clinical trials and were treated with 300 mg dupilumab weekly or every other week. Concomitant treatments were permitted, including topical corticosteroids and topical calcineurin inhibitors. (The proportion of patients dosed on an every-other-week or weekly dosing schedule was not available.)

Of 334 patients (12.5%) who remained in the trial at week 260, or 5 years, 88.9% achieved at least a 75% improvement in lesion extent and severity (Eczema Area and Severity Index [EASI]-75), and 76.2% achieved an EASI-90. The proportion achieving at least a 4-point reduction in the Peak Pruritus Numerical Rating Scale (NRS) or a score of 0 was 66.5%. At 5 years, improvements “seem very stable,” with “no loss in efficacy,” Dr. Beck said.

The majority of patients who withdrew from the open-label extension trial did so because the study was terminated at their site or because of the drug’s approval and commercialization – not for a medical reason, Dr. Beck said. Over the course of the extension trial, 4% of those enrolled withdrew because of adverse events and about 2% withdrew because of lack of efficacy.

Safety of dupilumab

The extension trial lacked a control arm, so Dr. Beck and her colleagues compared safety results to those in the final data set for patients in the LIBERTY AD CHRONOS study who received dupilumab 300 mg weekly with concomitant corticosteroids. The CHRONOS study was a 1-year randomized, double-blinded placebo-controlled phase 3 trial.

The exposure-adjusted incidence rate of severe treatment-emergent adverse events (TEAE) was lower at the close of the extension trial (5 patients/100 patient years [PY]) than at the end of the CHRONOS study (5.9 patients/100 PY). The incidence of serious adverse events related to treatment was 0.6 patients/100 PY in the final open label extension study data set, compared with 0.7 patients/100 PY in the CHRONOS final data set.

Adverse event rates “are really, if anything, slightly less in the OLE study versus the CHRONOS study, which was 1 year of treatment,” Dr. Beck said. And “no new adverse events have emerged.”

During a question and answer period, Dr. Beck pointed out that existing and future “real world” registries of patients on dupilumab and other new therapies will better inform dermatologists of adverse events than clinical trials have done.
 

Ocular surface disease

In a separate presentation on the safety of biologics, Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, Portland, said that in routine care, ocular surface disease is the most predominant side effect associated with dupilumab. “We don’t know the mechanism of action. But it’s not infectious, it’s not pink eye, and importantly, it’s not allergic conjunctivitis,” he said, noting that the spectrum of disease ranges from dry eye and eye itching to “frank conjunctivitis” and keratitis.

Most cases are mild to moderate and can often be managed with lubricating eye drops and periodic use of corticosteroid eye drops. Co-management with an ophthalmologist is often advisable, he said.

Dupilumab-associated erythema/eczema of the face was “not seen much” in clinical trials but is also being reported in the literature, largely by European researchers, Dr. Blauvelt said. “We hear a lot about red face, but I don’t think it’s much of an issue,” he said. “Most of the time, in my experience, it will [reflect] breakthrough residual AD, and I like to treat it with non-steroidal topicals.”

Occasionally, the withdrawal of steroids or allergic contact dermatitis are at play, Dr. Blauvelt said. “If you see red face in a person on dupilumab, use your clinical prowess, do a differential diagnosis, and treat accordingly.”
 

Effect on S. aureus

The vast majority of adults with moderate to severe AD have skin colonization with S. aureus, Dr. Beck said during the session on long-term control of AD. The presence of S. aureus in skin cultures correlates strongly with AD severity, type 2 immunity polarization, skin barrier disruption, and allergen sensitization, she said.

“So if we could do something to get rid of the staph and keep it away, one might imagine that would help” control the AD disease process, she said.

An ADRN study evaluated S. aureus in the skin of 71 patients who were randomized to receive dupilumab or placebo and found a “profound” effect of the biologic. “We were truly shocked by how quickly we saw a reduction in Staph aureus ... in lesional skin as early as 3 days” into treatment with dupilumab, she said of the unpublished findings. “And there is a pretty nice association with improvement in disease severity.”

Dr. Beck reported consultancy/advisory board work with Regeneron, Sanofi/Genzyme, among other disclosures. Dr. Blauvelt reported consultancy/advisory board work for Regeneron and Sanofi Genzyme and has received speakers bureau/honoraria for non-CME work for Regeneron and Sanofi, among other disclosures.

WASHINGTON – The LIBERTY AD open-label extension study of dupilumab is closing after 5 years with the small number of remaining patients showing stable and sustained improvements in skin lesions and pruritus and no new emergent side effects, Lisa Beck, MD, reported during a late-breaking session at the annual Revolutionizing Atopic Dermatitis conference.

Other recent research on the biologic has shown that it improves lesional skin barrier function and rapidly reduces the abundance of Staphylococcus aureus on lesional skin, Dr. Beck, professor of dermatology at the University of Rochester (N.Y.), said during another session at the meeting on long-term control of AD. Dr. Beck directs a laboratory at the University of Rochester Medical Center that focuses on understanding AD and is involved in the National Institute of Allergy and Infectious Diseases (NIAID)-funded Atopic Dermatitis Research Network (ADRN).

The LIBERTY AD open-label extension (OLE) study was a phase 3 trial of 2,677 adults with moderate to severe AD who had participated in previous dupilumab clinical trials and were treated with 300 mg dupilumab weekly or every other week. Concomitant treatments were permitted, including topical corticosteroids and topical calcineurin inhibitors. (The proportion of patients dosed on an every-other-week or weekly dosing schedule was not available.)

Of 334 patients (12.5%) who remained in the trial at week 260, or 5 years, 88.9% achieved at least a 75% improvement in lesion extent and severity (Eczema Area and Severity Index [EASI]-75), and 76.2% achieved an EASI-90. The proportion achieving at least a 4-point reduction in the Peak Pruritus Numerical Rating Scale (NRS) or a score of 0 was 66.5%. At 5 years, improvements “seem very stable,” with “no loss in efficacy,” Dr. Beck said.

The majority of patients who withdrew from the open-label extension trial did so because the study was terminated at their site or because of the drug’s approval and commercialization – not for a medical reason, Dr. Beck said. Over the course of the extension trial, 4% of those enrolled withdrew because of adverse events and about 2% withdrew because of lack of efficacy.

Safety of dupilumab

The extension trial lacked a control arm, so Dr. Beck and her colleagues compared safety results to those in the final data set for patients in the LIBERTY AD CHRONOS study who received dupilumab 300 mg weekly with concomitant corticosteroids. The CHRONOS study was a 1-year randomized, double-blinded placebo-controlled phase 3 trial.

The exposure-adjusted incidence rate of severe treatment-emergent adverse events (TEAE) was lower at the close of the extension trial (5 patients/100 patient years [PY]) than at the end of the CHRONOS study (5.9 patients/100 PY). The incidence of serious adverse events related to treatment was 0.6 patients/100 PY in the final open label extension study data set, compared with 0.7 patients/100 PY in the CHRONOS final data set.

Adverse event rates “are really, if anything, slightly less in the OLE study versus the CHRONOS study, which was 1 year of treatment,” Dr. Beck said. And “no new adverse events have emerged.”

During a question and answer period, Dr. Beck pointed out that existing and future “real world” registries of patients on dupilumab and other new therapies will better inform dermatologists of adverse events than clinical trials have done.
 

Ocular surface disease

In a separate presentation on the safety of biologics, Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, Portland, said that in routine care, ocular surface disease is the most predominant side effect associated with dupilumab. “We don’t know the mechanism of action. But it’s not infectious, it’s not pink eye, and importantly, it’s not allergic conjunctivitis,” he said, noting that the spectrum of disease ranges from dry eye and eye itching to “frank conjunctivitis” and keratitis.

Most cases are mild to moderate and can often be managed with lubricating eye drops and periodic use of corticosteroid eye drops. Co-management with an ophthalmologist is often advisable, he said.

Dupilumab-associated erythema/eczema of the face was “not seen much” in clinical trials but is also being reported in the literature, largely by European researchers, Dr. Blauvelt said. “We hear a lot about red face, but I don’t think it’s much of an issue,” he said. “Most of the time, in my experience, it will [reflect] breakthrough residual AD, and I like to treat it with non-steroidal topicals.”

Occasionally, the withdrawal of steroids or allergic contact dermatitis are at play, Dr. Blauvelt said. “If you see red face in a person on dupilumab, use your clinical prowess, do a differential diagnosis, and treat accordingly.”
 

Effect on S. aureus

The vast majority of adults with moderate to severe AD have skin colonization with S. aureus, Dr. Beck said during the session on long-term control of AD. The presence of S. aureus in skin cultures correlates strongly with AD severity, type 2 immunity polarization, skin barrier disruption, and allergen sensitization, she said.

“So if we could do something to get rid of the staph and keep it away, one might imagine that would help” control the AD disease process, she said.

An ADRN study evaluated S. aureus in the skin of 71 patients who were randomized to receive dupilumab or placebo and found a “profound” effect of the biologic. “We were truly shocked by how quickly we saw a reduction in Staph aureus ... in lesional skin as early as 3 days” into treatment with dupilumab, she said of the unpublished findings. “And there is a pretty nice association with improvement in disease severity.”

Dr. Beck reported consultancy/advisory board work with Regeneron, Sanofi/Genzyme, among other disclosures. Dr. Blauvelt reported consultancy/advisory board work for Regeneron and Sanofi Genzyme and has received speakers bureau/honoraria for non-CME work for Regeneron and Sanofi, among other disclosures.

WASHINGTON – The LIBERTY AD open-label extension study of dupilumab is closing after 5 years with the small number of remaining patients showing stable and sustained improvements in skin lesions and pruritus and no new emergent side effects, Lisa Beck, MD, reported during a late-breaking session at the annual Revolutionizing Atopic Dermatitis conference.

Other recent research on the biologic has shown that it improves lesional skin barrier function and rapidly reduces the abundance of Staphylococcus aureus on lesional skin, Dr. Beck, professor of dermatology at the University of Rochester (N.Y.), said during another session at the meeting on long-term control of AD. Dr. Beck directs a laboratory at the University of Rochester Medical Center that focuses on understanding AD and is involved in the National Institute of Allergy and Infectious Diseases (NIAID)-funded Atopic Dermatitis Research Network (ADRN).

The LIBERTY AD open-label extension (OLE) study was a phase 3 trial of 2,677 adults with moderate to severe AD who had participated in previous dupilumab clinical trials and were treated with 300 mg dupilumab weekly or every other week. Concomitant treatments were permitted, including topical corticosteroids and topical calcineurin inhibitors. (The proportion of patients dosed on an every-other-week or weekly dosing schedule was not available.)

Of 334 patients (12.5%) who remained in the trial at week 260, or 5 years, 88.9% achieved at least a 75% improvement in lesion extent and severity (Eczema Area and Severity Index [EASI]-75), and 76.2% achieved an EASI-90. The proportion achieving at least a 4-point reduction in the Peak Pruritus Numerical Rating Scale (NRS) or a score of 0 was 66.5%. At 5 years, improvements “seem very stable,” with “no loss in efficacy,” Dr. Beck said.

The majority of patients who withdrew from the open-label extension trial did so because the study was terminated at their site or because of the drug’s approval and commercialization – not for a medical reason, Dr. Beck said. Over the course of the extension trial, 4% of those enrolled withdrew because of adverse events and about 2% withdrew because of lack of efficacy.

Safety of dupilumab

The extension trial lacked a control arm, so Dr. Beck and her colleagues compared safety results to those in the final data set for patients in the LIBERTY AD CHRONOS study who received dupilumab 300 mg weekly with concomitant corticosteroids. The CHRONOS study was a 1-year randomized, double-blinded placebo-controlled phase 3 trial.

The exposure-adjusted incidence rate of severe treatment-emergent adverse events (TEAE) was lower at the close of the extension trial (5 patients/100 patient years [PY]) than at the end of the CHRONOS study (5.9 patients/100 PY). The incidence of serious adverse events related to treatment was 0.6 patients/100 PY in the final open label extension study data set, compared with 0.7 patients/100 PY in the CHRONOS final data set.

Adverse event rates “are really, if anything, slightly less in the OLE study versus the CHRONOS study, which was 1 year of treatment,” Dr. Beck said. And “no new adverse events have emerged.”

During a question and answer period, Dr. Beck pointed out that existing and future “real world” registries of patients on dupilumab and other new therapies will better inform dermatologists of adverse events than clinical trials have done.
 

Ocular surface disease

In a separate presentation on the safety of biologics, Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, Portland, said that in routine care, ocular surface disease is the most predominant side effect associated with dupilumab. “We don’t know the mechanism of action. But it’s not infectious, it’s not pink eye, and importantly, it’s not allergic conjunctivitis,” he said, noting that the spectrum of disease ranges from dry eye and eye itching to “frank conjunctivitis” and keratitis.

Most cases are mild to moderate and can often be managed with lubricating eye drops and periodic use of corticosteroid eye drops. Co-management with an ophthalmologist is often advisable, he said.

Dupilumab-associated erythema/eczema of the face was “not seen much” in clinical trials but is also being reported in the literature, largely by European researchers, Dr. Blauvelt said. “We hear a lot about red face, but I don’t think it’s much of an issue,” he said. “Most of the time, in my experience, it will [reflect] breakthrough residual AD, and I like to treat it with non-steroidal topicals.”

Occasionally, the withdrawal of steroids or allergic contact dermatitis are at play, Dr. Blauvelt said. “If you see red face in a person on dupilumab, use your clinical prowess, do a differential diagnosis, and treat accordingly.”
 

Effect on S. aureus

The vast majority of adults with moderate to severe AD have skin colonization with S. aureus, Dr. Beck said during the session on long-term control of AD. The presence of S. aureus in skin cultures correlates strongly with AD severity, type 2 immunity polarization, skin barrier disruption, and allergen sensitization, she said.

“So if we could do something to get rid of the staph and keep it away, one might imagine that would help” control the AD disease process, she said.

An ADRN study evaluated S. aureus in the skin of 71 patients who were randomized to receive dupilumab or placebo and found a “profound” effect of the biologic. “We were truly shocked by how quickly we saw a reduction in Staph aureus ... in lesional skin as early as 3 days” into treatment with dupilumab, she said of the unpublished findings. “And there is a pretty nice association with improvement in disease severity.”

Dr. Beck reported consultancy/advisory board work with Regeneron, Sanofi/Genzyme, among other disclosures. Dr. Blauvelt reported consultancy/advisory board work for Regeneron and Sanofi Genzyme and has received speakers bureau/honoraria for non-CME work for Regeneron and Sanofi, among other disclosures.

MILAN – Targeted synthetic and biologic therapies are recommended as disease-modifying agents for key fibrotic manifestations of systemic sclerosis for the first time in the 2023 update of European Alliance of Associations for Rheumatology recommendations for the treatment of systemic sclerosis.

Reflecting important advances over the past 8 years, mostly relating to the use of new treatments being made available to patients, the recommendations provide an update on the 2017 recommendations, which relied on evidence published through 2014. Of note, these include the use of immunosuppressive agents, for example, the monoclonal antibody rituximab (Rituxan) for skin and lung fibrosis.

“For the first time, synthetic and targeted treatments are recommended for the treatment of systemic sclerosis–interstitial lung disease, including mycophenolate mofetil [Cellcept], nintedanib [Ofev], rituximab, and tocilizumab [Actemra]. None of these were present in 2017. Mycophenolate mofetil is also recommended for the treatment of skin fibrosis, and this was not present in 2017,” Francesco Del Galdo, MD, rheumatology consultant at Leeds Teaching Hospital NHS Trust, Leeds, England, and member of the 2023 recommendations task force, said in an interview. He gave an overview of the preliminary recommendations at the annual European Congress of Rheumatology.

“Phosphodiesterase-5 [PDE-5] inhibitors and endothelin receptor antagonist [ERA] monotherapy are also recommended for up-front combination use for digital ulcers and pulmonary hypertension, and this is new for 2023 and was not present in the 2017 recommendations,” Dr. Del Galdo added.

The new recommendations also note that iloprost is categorized as having grade A evidence for use in Raynaud’s phenomenon and digital ulcers, while it has grade B evidence for pulmonary hypertension.

“We are not allowed to share the final table [of recommendations] today because the wording has only very recently been agreed” upon, Dr. Del Galdo said, but he provided a summary representation and reflected on some changes, noting that the task force is aiming to publish the 2023 recommendations by the end of the year.

Consideration and discussion of both established and new evidence highlighted a need for more evidence on the use of immunosuppressive agents in vascular manifestations of systemic sclerosis, as well as for gastrointestinal and musculoskeletal ones.

In this update to the 2017 recommendations, high-grade evidence was identified for use of immunosuppressants in skin and lung fibrosis. Grade A evidence has been accepted for the use of rituximab in skin fibrosis; for interstitial lung disease, rituximab, cyclophosphamide, and nintedanib also have grade A evidence, which is a change from the 2017 recommendations.

A total of 20 updated recommendations were agreed on, an increase from 16 in 2017. These were grouped into eight disease domains: Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, skin fibrosis, interstitial lung disease, musculoskeletal and gastrointestinal manifestations, and renal crisis. Interventions were then graded A-D based on the evidence reviewed.

“This approach allowed us to see clearly that there were patterns of similar recommendations in different organ manifestations, reflecting an understanding of common pathogenic pathways,” said Dr. Del Galdo.

He also noted that the development of the recommendations highlighted certain gaps in research that limit treatment options. “By grouping the recommendations in blocks – for example, skin fibrosis or vascular [manifestations] – we show that immunosuppressive treatments have only been studied in skin and lung, while vascular manifestations have very little evidence for immunosuppression. They might be effective but there’s no evidence yet [hence no recommendation in vascular manifestations].”

“Also, there’s no grade A evidence at all for musculoskeletal and gastrointestinal manifestations, and this should help to define the research agenda going forward,” Dr. Del Galdo said.

The 2023 recommendations task force comprised 28 members from 14 countries, including 18 rheumatologists, 1 EULAR methodologist, 1 health professional representative, 5 rheumatology fellows, 1 librarian, and 2 patient representatives. They used a consensual approach incorporating the views of 101 European Scleroderma Trials and Research group (EUSTAR) centers, sourced via a survey in which questions were advanced to an extensive systematic review if there was 70% or greater agreement.

Eventually, 31 questions on interventions were chosen, and the task force reviewed 12,500 abstracts (up to December 2022) related to interventions and outcomes that were either included in the 2017 recommendations or were totally new.

Dr. Del Galdo said that the three vascular manifestations of scleroderma – Raynaud’s, pulmonary arterial hypertension, and digital ulcers – were treated with the same drugs, all with a similar grade of evidence. “This suggests two things – firstly there’s a vascular disease continuum in the disease, and secondly, we’ve borrowed these drugs from vascular community, but we have not yet tested synthetic and biologic targeted treatments in these manifestations, and we should.

“Treating one manifestation may benefit the other, and this is important time wise because pulmonary hypertension usually comes around 10 years after the first phenomena so by treating digital ulcers and Raynaud’s phenomena, we may prevent pulmonary hypertension, but a study is needed,” added Dr. Del Galdo, who is also president of EUSTAR.

Finally, he pointed out that research remains particularly open for nonpharmacologic treatments for digital ulcers and severe gastrointestinal involvement. “Patients can now ask for studies into this because of the current lack of evidence.”

Moderator Ariane Herrick, PhD, professor of rheumatology at the University of Manchester (England), shared her thoughts on the guidelines. “These recommendations have been long awaited by the scleroderma community because there has been some exciting progress in recent years, and the new recommendations reflect these new developments.”

Commenting on the paucity of evidence in some areas, she added that “there do remain some huge areas of unmet need that are difficult to address, and these are musculoskeletal, gastrointestinal, and calcinosis, for which there have been no trials at all.”

Dr. Del Galdo declared disclosures relating to AstraZeneca, Janssen, Boehringer Ingelheim, Capella, Chemomab, GlaxoSmithKline, and Mitsubishi-Tanabe. Dr. Herrick disclosed serving as a consultant for Boehringer Ingelheim and Janssen.

MILAN – Targeted synthetic and biologic therapies are recommended as disease-modifying agents for key fibrotic manifestations of systemic sclerosis for the first time in the 2023 update of European Alliance of Associations for Rheumatology recommendations for the treatment of systemic sclerosis.

Reflecting important advances over the past 8 years, mostly relating to the use of new treatments being made available to patients, the recommendations provide an update on the 2017 recommendations, which relied on evidence published through 2014. Of note, these include the use of immunosuppressive agents, for example, the monoclonal antibody rituximab (Rituxan) for skin and lung fibrosis.

“For the first time, synthetic and targeted treatments are recommended for the treatment of systemic sclerosis–interstitial lung disease, including mycophenolate mofetil [Cellcept], nintedanib [Ofev], rituximab, and tocilizumab [Actemra]. None of these were present in 2017. Mycophenolate mofetil is also recommended for the treatment of skin fibrosis, and this was not present in 2017,” Francesco Del Galdo, MD, rheumatology consultant at Leeds Teaching Hospital NHS Trust, Leeds, England, and member of the 2023 recommendations task force, said in an interview. He gave an overview of the preliminary recommendations at the annual European Congress of Rheumatology.

“Phosphodiesterase-5 [PDE-5] inhibitors and endothelin receptor antagonist [ERA] monotherapy are also recommended for up-front combination use for digital ulcers and pulmonary hypertension, and this is new for 2023 and was not present in the 2017 recommendations,” Dr. Del Galdo added.

The new recommendations also note that iloprost is categorized as having grade A evidence for use in Raynaud’s phenomenon and digital ulcers, while it has grade B evidence for pulmonary hypertension.

“We are not allowed to share the final table [of recommendations] today because the wording has only very recently been agreed” upon, Dr. Del Galdo said, but he provided a summary representation and reflected on some changes, noting that the task force is aiming to publish the 2023 recommendations by the end of the year.

Consideration and discussion of both established and new evidence highlighted a need for more evidence on the use of immunosuppressive agents in vascular manifestations of systemic sclerosis, as well as for gastrointestinal and musculoskeletal ones.

In this update to the 2017 recommendations, high-grade evidence was identified for use of immunosuppressants in skin and lung fibrosis. Grade A evidence has been accepted for the use of rituximab in skin fibrosis; for interstitial lung disease, rituximab, cyclophosphamide, and nintedanib also have grade A evidence, which is a change from the 2017 recommendations.

A total of 20 updated recommendations were agreed on, an increase from 16 in 2017. These were grouped into eight disease domains: Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, skin fibrosis, interstitial lung disease, musculoskeletal and gastrointestinal manifestations, and renal crisis. Interventions were then graded A-D based on the evidence reviewed.

“This approach allowed us to see clearly that there were patterns of similar recommendations in different organ manifestations, reflecting an understanding of common pathogenic pathways,” said Dr. Del Galdo.

He also noted that the development of the recommendations highlighted certain gaps in research that limit treatment options. “By grouping the recommendations in blocks – for example, skin fibrosis or vascular [manifestations] – we show that immunosuppressive treatments have only been studied in skin and lung, while vascular manifestations have very little evidence for immunosuppression. They might be effective but there’s no evidence yet [hence no recommendation in vascular manifestations].”

“Also, there’s no grade A evidence at all for musculoskeletal and gastrointestinal manifestations, and this should help to define the research agenda going forward,” Dr. Del Galdo said.

The 2023 recommendations task force comprised 28 members from 14 countries, including 18 rheumatologists, 1 EULAR methodologist, 1 health professional representative, 5 rheumatology fellows, 1 librarian, and 2 patient representatives. They used a consensual approach incorporating the views of 101 European Scleroderma Trials and Research group (EUSTAR) centers, sourced via a survey in which questions were advanced to an extensive systematic review if there was 70% or greater agreement.

Eventually, 31 questions on interventions were chosen, and the task force reviewed 12,500 abstracts (up to December 2022) related to interventions and outcomes that were either included in the 2017 recommendations or were totally new.

Dr. Del Galdo said that the three vascular manifestations of scleroderma – Raynaud’s, pulmonary arterial hypertension, and digital ulcers – were treated with the same drugs, all with a similar grade of evidence. “This suggests two things – firstly there’s a vascular disease continuum in the disease, and secondly, we’ve borrowed these drugs from vascular community, but we have not yet tested synthetic and biologic targeted treatments in these manifestations, and we should.

“Treating one manifestation may benefit the other, and this is important time wise because pulmonary hypertension usually comes around 10 years after the first phenomena so by treating digital ulcers and Raynaud’s phenomena, we may prevent pulmonary hypertension, but a study is needed,” added Dr. Del Galdo, who is also president of EUSTAR.

Finally, he pointed out that research remains particularly open for nonpharmacologic treatments for digital ulcers and severe gastrointestinal involvement. “Patients can now ask for studies into this because of the current lack of evidence.”

Moderator Ariane Herrick, PhD, professor of rheumatology at the University of Manchester (England), shared her thoughts on the guidelines. “These recommendations have been long awaited by the scleroderma community because there has been some exciting progress in recent years, and the new recommendations reflect these new developments.”

Commenting on the paucity of evidence in some areas, she added that “there do remain some huge areas of unmet need that are difficult to address, and these are musculoskeletal, gastrointestinal, and calcinosis, for which there have been no trials at all.”

Dr. Del Galdo declared disclosures relating to AstraZeneca, Janssen, Boehringer Ingelheim, Capella, Chemomab, GlaxoSmithKline, and Mitsubishi-Tanabe. Dr. Herrick disclosed serving as a consultant for Boehringer Ingelheim and Janssen.

MILAN – Targeted synthetic and biologic therapies are recommended as disease-modifying agents for key fibrotic manifestations of systemic sclerosis for the first time in the 2023 update of European Alliance of Associations for Rheumatology recommendations for the treatment of systemic sclerosis.

Reflecting important advances over the past 8 years, mostly relating to the use of new treatments being made available to patients, the recommendations provide an update on the 2017 recommendations, which relied on evidence published through 2014. Of note, these include the use of immunosuppressive agents, for example, the monoclonal antibody rituximab (Rituxan) for skin and lung fibrosis.

“For the first time, synthetic and targeted treatments are recommended for the treatment of systemic sclerosis–interstitial lung disease, including mycophenolate mofetil [Cellcept], nintedanib [Ofev], rituximab, and tocilizumab [Actemra]. None of these were present in 2017. Mycophenolate mofetil is also recommended for the treatment of skin fibrosis, and this was not present in 2017,” Francesco Del Galdo, MD, rheumatology consultant at Leeds Teaching Hospital NHS Trust, Leeds, England, and member of the 2023 recommendations task force, said in an interview. He gave an overview of the preliminary recommendations at the annual European Congress of Rheumatology.

“Phosphodiesterase-5 [PDE-5] inhibitors and endothelin receptor antagonist [ERA] monotherapy are also recommended for up-front combination use for digital ulcers and pulmonary hypertension, and this is new for 2023 and was not present in the 2017 recommendations,” Dr. Del Galdo added.

The new recommendations also note that iloprost is categorized as having grade A evidence for use in Raynaud’s phenomenon and digital ulcers, while it has grade B evidence for pulmonary hypertension.

“We are not allowed to share the final table [of recommendations] today because the wording has only very recently been agreed” upon, Dr. Del Galdo said, but he provided a summary representation and reflected on some changes, noting that the task force is aiming to publish the 2023 recommendations by the end of the year.

Consideration and discussion of both established and new evidence highlighted a need for more evidence on the use of immunosuppressive agents in vascular manifestations of systemic sclerosis, as well as for gastrointestinal and musculoskeletal ones.

In this update to the 2017 recommendations, high-grade evidence was identified for use of immunosuppressants in skin and lung fibrosis. Grade A evidence has been accepted for the use of rituximab in skin fibrosis; for interstitial lung disease, rituximab, cyclophosphamide, and nintedanib also have grade A evidence, which is a change from the 2017 recommendations.

A total of 20 updated recommendations were agreed on, an increase from 16 in 2017. These were grouped into eight disease domains: Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, skin fibrosis, interstitial lung disease, musculoskeletal and gastrointestinal manifestations, and renal crisis. Interventions were then graded A-D based on the evidence reviewed.

“This approach allowed us to see clearly that there were patterns of similar recommendations in different organ manifestations, reflecting an understanding of common pathogenic pathways,” said Dr. Del Galdo.

He also noted that the development of the recommendations highlighted certain gaps in research that limit treatment options. “By grouping the recommendations in blocks – for example, skin fibrosis or vascular [manifestations] – we show that immunosuppressive treatments have only been studied in skin and lung, while vascular manifestations have very little evidence for immunosuppression. They might be effective but there’s no evidence yet [hence no recommendation in vascular manifestations].”

“Also, there’s no grade A evidence at all for musculoskeletal and gastrointestinal manifestations, and this should help to define the research agenda going forward,” Dr. Del Galdo said.

The 2023 recommendations task force comprised 28 members from 14 countries, including 18 rheumatologists, 1 EULAR methodologist, 1 health professional representative, 5 rheumatology fellows, 1 librarian, and 2 patient representatives. They used a consensual approach incorporating the views of 101 European Scleroderma Trials and Research group (EUSTAR) centers, sourced via a survey in which questions were advanced to an extensive systematic review if there was 70% or greater agreement.

Eventually, 31 questions on interventions were chosen, and the task force reviewed 12,500 abstracts (up to December 2022) related to interventions and outcomes that were either included in the 2017 recommendations or were totally new.

Dr. Del Galdo said that the three vascular manifestations of scleroderma – Raynaud’s, pulmonary arterial hypertension, and digital ulcers – were treated with the same drugs, all with a similar grade of evidence. “This suggests two things – firstly there’s a vascular disease continuum in the disease, and secondly, we’ve borrowed these drugs from vascular community, but we have not yet tested synthetic and biologic targeted treatments in these manifestations, and we should.

“Treating one manifestation may benefit the other, and this is important time wise because pulmonary hypertension usually comes around 10 years after the first phenomena so by treating digital ulcers and Raynaud’s phenomena, we may prevent pulmonary hypertension, but a study is needed,” added Dr. Del Galdo, who is also president of EUSTAR.

Finally, he pointed out that research remains particularly open for nonpharmacologic treatments for digital ulcers and severe gastrointestinal involvement. “Patients can now ask for studies into this because of the current lack of evidence.”

Moderator Ariane Herrick, PhD, professor of rheumatology at the University of Manchester (England), shared her thoughts on the guidelines. “These recommendations have been long awaited by the scleroderma community because there has been some exciting progress in recent years, and the new recommendations reflect these new developments.”

Commenting on the paucity of evidence in some areas, she added that “there do remain some huge areas of unmet need that are difficult to address, and these are musculoskeletal, gastrointestinal, and calcinosis, for which there have been no trials at all.”

Dr. Del Galdo declared disclosures relating to AstraZeneca, Janssen, Boehringer Ingelheim, Capella, Chemomab, GlaxoSmithKline, and Mitsubishi-Tanabe. Dr. Herrick disclosed serving as a consultant for Boehringer Ingelheim and Janssen.

More than 600,000 Americans have lost Medicaid coverage since pandemic protections ended on April 1. And a KFF Health News analysis of state data shows the vast majority were removed from state rolls for not completing paperwork.

Under normal circumstances, states review their Medicaid enrollment lists regularly to ensure every recipient qualifies for coverage. But because of a nationwide pause in those reviews during the pandemic, the health insurance program for low-income and disabled Americans kept people covered even if they no longer qualified.

Now, in what’s known as the Medicaid unwinding, states are combing through rolls and deciding who stays and who goes. People who are no longer eligible or don’t complete paperwork in time will be dropped.

The overwhelming majority of people who have lost coverage in most states were dropped because of technicalities, not because state officials determined they no longer meet Medicaid income limits. Four out of every five people dropped so far either never returned the paperwork or omitted required documents, according to a KFF Health News analysis of data from 11 states that provided details on recent cancellations. Now, lawmakers and advocates are expressing alarm over the volume of people losing coverage and, in some states, calling to pause the process.

KFF Health News sought data from the 19 states that started cancellations by May 1. Based on records from 14 states that provided detailed numbers, either in response to a public records request or by posting online, 36% of people whose eligibility was reviewed have been disenrolled.

In Indiana, 53,000 residents lost coverage in the first month of the unwinding, 89% for procedural reasons like not returning renewal forms. State Rep. Ed Clere, a Republican, expressed dismay at those “staggering numbers” in a May 24 Medicaid advisory group meeting, repeatedly questioning state officials about forms mailed to out-of-date addresses and urging them to give people more than 2 weeks’ notice before canceling their coverage.

Rep. Clere warned that the cancellations set in motion an avoidable revolving door. Some people dropped from Medicaid will have to forgo filling prescriptions and cancel doctor visits because they can’t afford care. Months down the line, after untreated chronic illnesses spiral out of control, they’ll end up in the emergency room where social workers will need to again help them join the program, he said.

Before the unwinding, more than one in four Americans – 93 million – were covered by Medicaid or CHIP, the Children’s Health Insurance Program, according to KFF Health News’ analysis of the latest enrollment data. Half of all kids are covered by the programs.

About 15 million people will be dropped over the next year as states review participants’ eligibility in monthly tranches.

Most people will find health coverage through new jobs or qualify for subsidized plans through the Affordable Care Act. But millions of others, including many children, will become uninsured and unable to afford basic prescriptions or preventive care. The uninsured rate among those under 65 is projected to rise from a historical low of 8.3% today to 9.3% next year, according to the Congressional Budget Office.

Because each state is handling the unwinding differently, the share of enrollees dropped in the first weeks varies widely.

Several states are first reviewing people officials believe are no longer eligible or who haven’t recently used their insurance. High cancellation rates in those states should level out as the agencies move on to people who likely still qualify.

In Utah, nearly 56% of people included in early reviews were dropped. In New Hampshire, 44% received cancellation letters within the first 2 months – almost all for procedural reasons, like not returning paperwork.

But New Hampshire officials found that thousands of people who didn’t fill out the forms indeed earn too much to qualify, according to Henry Lipman, the state’s Medicaid director. They would have been denied anyway. Even so, more people than he expected are not returning renewal forms. “That tells us that we need to change up our strategy,” said Mr. Lipman.

In other states, like Virginia and Nebraska, which aren’t prioritizing renewals by likely eligibility, about 90% have been renewed.

Because of the 3-year pause in renewals, many people on Medicaid have never been through the process or aren’t aware they may need to fill out long verification forms, as a recent KFF poll found. Some people moved and didn’t update their contact information.

And while agencies are required to assist enrollees who don’t speak English well, many are sending the forms in only a few common languages.

Tens of thousands of children are losing coverage, as researchers have warned, even though some may still qualify for Medicaid or CHIP. In its first month of reviews, South Dakota ended coverage for 10% of all Medicaid and CHIP enrollees in the state. More than half of them were children. In Arkansas, about 40% were kids.

Many parents don’t know that limits on household income are significantly higher for children than adults. Parents should fill out renewal forms even if they don’t qualify themselves, said Joan Alker, executive director of the Georgetown University Center for Children and Families, Washington.

New Hampshire has moved most families with children to the end of the review process. Mr. Lipman said his biggest worry is that a child will end up uninsured. Florida also planned to push kids with serious health conditions and other vulnerable groups to the end of the review line.

But according to Miriam Harmatz, advocacy director and founder of the Florida Health Justice Project, state officials sent cancellation letters to several clients with disabled children who probably still qualify. She’s helping those families appeal.

Nearly 250,000 Floridians reviewed in the first month of the unwinding lost coverage, 82% of them for reasons like incomplete paperwork, the state reported to federal authorities. House Democrats from the state petitioned Republican Gov. Ron DeSantis to pause the unwinding.

Advocacy coalitions in both Florida and Arkansas also have called for investigations into the review process and a pause on cancellations.

The state is contacting enrollees by phone, email, and text, and continues to process late applications, said Tori Cuddy, a spokesperson for the Florida Department of Children and Families. Ms. Cuddy did not respond to questions about issues raised in the petitions.

Federal officials are investigating those complaints and any other problems that emerge, said Dan Tsai, director of the Center for Medicaid & CHIP Services. “If we find that the rules are not being followed, we will take action.”

His agency has directed states to automatically reenroll residents using data from other government programs like unemployment and food assistance when possible. Anyone who can’t be approved through that process must act quickly.

“For the past 3 years, people have been told to ignore the mail around this, that the renewal was not going to lead to a termination.” Suddenly that mail matters, he said.

Federal law requires states to tell people why they’re losing Medicaid coverage and how to appeal the decision.

Ms. Harmatz said some cancellation notices in Florida are vague and could violate due process rules. Letters that she’s seen say “your Medicaid for this period is ending” rather than providing a specific reason for disenrollment, like having too high an income or incomplete paperwork.
If a person requests a hearing before their cancellation takes effect, they can stay covered during the appeals process. Even after being disenrolled, many still have a 90-day window to restore coverage.

In New Hampshire, 13% of people deemed ineligible in the first month have asked for extra time to provide the necessary records. “If you’re eligible for Medicaid, we don’t want you to lose it,” said Mr. Lipman.

Rep. Clere pushed Indiana’s Medicaid officials during the May meeting to immediately make changes to avoid people unnecessarily becoming uninsured. One official responded that they’ll learn and improve over time.

“I’m just concerned that we’re going to be ‘learning’ as a result of people losing coverage,” Rep. Clere replied. “So I don’t want to learn at their expense.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

More than 600,000 Americans have lost Medicaid coverage since pandemic protections ended on April 1. And a KFF Health News analysis of state data shows the vast majority were removed from state rolls for not completing paperwork.

Under normal circumstances, states review their Medicaid enrollment lists regularly to ensure every recipient qualifies for coverage. But because of a nationwide pause in those reviews during the pandemic, the health insurance program for low-income and disabled Americans kept people covered even if they no longer qualified.

Now, in what’s known as the Medicaid unwinding, states are combing through rolls and deciding who stays and who goes. People who are no longer eligible or don’t complete paperwork in time will be dropped.

The overwhelming majority of people who have lost coverage in most states were dropped because of technicalities, not because state officials determined they no longer meet Medicaid income limits. Four out of every five people dropped so far either never returned the paperwork or omitted required documents, according to a KFF Health News analysis of data from 11 states that provided details on recent cancellations. Now, lawmakers and advocates are expressing alarm over the volume of people losing coverage and, in some states, calling to pause the process.

KFF Health News sought data from the 19 states that started cancellations by May 1. Based on records from 14 states that provided detailed numbers, either in response to a public records request or by posting online, 36% of people whose eligibility was reviewed have been disenrolled.

In Indiana, 53,000 residents lost coverage in the first month of the unwinding, 89% for procedural reasons like not returning renewal forms. State Rep. Ed Clere, a Republican, expressed dismay at those “staggering numbers” in a May 24 Medicaid advisory group meeting, repeatedly questioning state officials about forms mailed to out-of-date addresses and urging them to give people more than 2 weeks’ notice before canceling their coverage.

Rep. Clere warned that the cancellations set in motion an avoidable revolving door. Some people dropped from Medicaid will have to forgo filling prescriptions and cancel doctor visits because they can’t afford care. Months down the line, after untreated chronic illnesses spiral out of control, they’ll end up in the emergency room where social workers will need to again help them join the program, he said.

Before the unwinding, more than one in four Americans – 93 million – were covered by Medicaid or CHIP, the Children’s Health Insurance Program, according to KFF Health News’ analysis of the latest enrollment data. Half of all kids are covered by the programs.

About 15 million people will be dropped over the next year as states review participants’ eligibility in monthly tranches.

Most people will find health coverage through new jobs or qualify for subsidized plans through the Affordable Care Act. But millions of others, including many children, will become uninsured and unable to afford basic prescriptions or preventive care. The uninsured rate among those under 65 is projected to rise from a historical low of 8.3% today to 9.3% next year, according to the Congressional Budget Office.

Because each state is handling the unwinding differently, the share of enrollees dropped in the first weeks varies widely.

Several states are first reviewing people officials believe are no longer eligible or who haven’t recently used their insurance. High cancellation rates in those states should level out as the agencies move on to people who likely still qualify.

In Utah, nearly 56% of people included in early reviews were dropped. In New Hampshire, 44% received cancellation letters within the first 2 months – almost all for procedural reasons, like not returning paperwork.

But New Hampshire officials found that thousands of people who didn’t fill out the forms indeed earn too much to qualify, according to Henry Lipman, the state’s Medicaid director. They would have been denied anyway. Even so, more people than he expected are not returning renewal forms. “That tells us that we need to change up our strategy,” said Mr. Lipman.

In other states, like Virginia and Nebraska, which aren’t prioritizing renewals by likely eligibility, about 90% have been renewed.

Because of the 3-year pause in renewals, many people on Medicaid have never been through the process or aren’t aware they may need to fill out long verification forms, as a recent KFF poll found. Some people moved and didn’t update their contact information.

And while agencies are required to assist enrollees who don’t speak English well, many are sending the forms in only a few common languages.

Tens of thousands of children are losing coverage, as researchers have warned, even though some may still qualify for Medicaid or CHIP. In its first month of reviews, South Dakota ended coverage for 10% of all Medicaid and CHIP enrollees in the state. More than half of them were children. In Arkansas, about 40% were kids.

Many parents don’t know that limits on household income are significantly higher for children than adults. Parents should fill out renewal forms even if they don’t qualify themselves, said Joan Alker, executive director of the Georgetown University Center for Children and Families, Washington.

New Hampshire has moved most families with children to the end of the review process. Mr. Lipman said his biggest worry is that a child will end up uninsured. Florida also planned to push kids with serious health conditions and other vulnerable groups to the end of the review line.

But according to Miriam Harmatz, advocacy director and founder of the Florida Health Justice Project, state officials sent cancellation letters to several clients with disabled children who probably still qualify. She’s helping those families appeal.

Nearly 250,000 Floridians reviewed in the first month of the unwinding lost coverage, 82% of them for reasons like incomplete paperwork, the state reported to federal authorities. House Democrats from the state petitioned Republican Gov. Ron DeSantis to pause the unwinding.

Advocacy coalitions in both Florida and Arkansas also have called for investigations into the review process and a pause on cancellations.

The state is contacting enrollees by phone, email, and text, and continues to process late applications, said Tori Cuddy, a spokesperson for the Florida Department of Children and Families. Ms. Cuddy did not respond to questions about issues raised in the petitions.

Federal officials are investigating those complaints and any other problems that emerge, said Dan Tsai, director of the Center for Medicaid & CHIP Services. “If we find that the rules are not being followed, we will take action.”

His agency has directed states to automatically reenroll residents using data from other government programs like unemployment and food assistance when possible. Anyone who can’t be approved through that process must act quickly.

“For the past 3 years, people have been told to ignore the mail around this, that the renewal was not going to lead to a termination.” Suddenly that mail matters, he said.

Federal law requires states to tell people why they’re losing Medicaid coverage and how to appeal the decision.

Ms. Harmatz said some cancellation notices in Florida are vague and could violate due process rules. Letters that she’s seen say “your Medicaid for this period is ending” rather than providing a specific reason for disenrollment, like having too high an income or incomplete paperwork.
If a person requests a hearing before their cancellation takes effect, they can stay covered during the appeals process. Even after being disenrolled, many still have a 90-day window to restore coverage.

In New Hampshire, 13% of people deemed ineligible in the first month have asked for extra time to provide the necessary records. “If you’re eligible for Medicaid, we don’t want you to lose it,” said Mr. Lipman.

Rep. Clere pushed Indiana’s Medicaid officials during the May meeting to immediately make changes to avoid people unnecessarily becoming uninsured. One official responded that they’ll learn and improve over time.

“I’m just concerned that we’re going to be ‘learning’ as a result of people losing coverage,” Rep. Clere replied. “So I don’t want to learn at their expense.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

More than 600,000 Americans have lost Medicaid coverage since pandemic protections ended on April 1. And a KFF Health News analysis of state data shows the vast majority were removed from state rolls for not completing paperwork.

Under normal circumstances, states review their Medicaid enrollment lists regularly to ensure every recipient qualifies for coverage. But because of a nationwide pause in those reviews during the pandemic, the health insurance program for low-income and disabled Americans kept people covered even if they no longer qualified.

Now, in what’s known as the Medicaid unwinding, states are combing through rolls and deciding who stays and who goes. People who are no longer eligible or don’t complete paperwork in time will be dropped.

The overwhelming majority of people who have lost coverage in most states were dropped because of technicalities, not because state officials determined they no longer meet Medicaid income limits. Four out of every five people dropped so far either never returned the paperwork or omitted required documents, according to a KFF Health News analysis of data from 11 states that provided details on recent cancellations. Now, lawmakers and advocates are expressing alarm over the volume of people losing coverage and, in some states, calling to pause the process.

KFF Health News sought data from the 19 states that started cancellations by May 1. Based on records from 14 states that provided detailed numbers, either in response to a public records request or by posting online, 36% of people whose eligibility was reviewed have been disenrolled.

In Indiana, 53,000 residents lost coverage in the first month of the unwinding, 89% for procedural reasons like not returning renewal forms. State Rep. Ed Clere, a Republican, expressed dismay at those “staggering numbers” in a May 24 Medicaid advisory group meeting, repeatedly questioning state officials about forms mailed to out-of-date addresses and urging them to give people more than 2 weeks’ notice before canceling their coverage.

Rep. Clere warned that the cancellations set in motion an avoidable revolving door. Some people dropped from Medicaid will have to forgo filling prescriptions and cancel doctor visits because they can’t afford care. Months down the line, after untreated chronic illnesses spiral out of control, they’ll end up in the emergency room where social workers will need to again help them join the program, he said.

Before the unwinding, more than one in four Americans – 93 million – were covered by Medicaid or CHIP, the Children’s Health Insurance Program, according to KFF Health News’ analysis of the latest enrollment data. Half of all kids are covered by the programs.

About 15 million people will be dropped over the next year as states review participants’ eligibility in monthly tranches.

Most people will find health coverage through new jobs or qualify for subsidized plans through the Affordable Care Act. But millions of others, including many children, will become uninsured and unable to afford basic prescriptions or preventive care. The uninsured rate among those under 65 is projected to rise from a historical low of 8.3% today to 9.3% next year, according to the Congressional Budget Office.

Because each state is handling the unwinding differently, the share of enrollees dropped in the first weeks varies widely.

Several states are first reviewing people officials believe are no longer eligible or who haven’t recently used their insurance. High cancellation rates in those states should level out as the agencies move on to people who likely still qualify.

In Utah, nearly 56% of people included in early reviews were dropped. In New Hampshire, 44% received cancellation letters within the first 2 months – almost all for procedural reasons, like not returning paperwork.

But New Hampshire officials found that thousands of people who didn’t fill out the forms indeed earn too much to qualify, according to Henry Lipman, the state’s Medicaid director. They would have been denied anyway. Even so, more people than he expected are not returning renewal forms. “That tells us that we need to change up our strategy,” said Mr. Lipman.

In other states, like Virginia and Nebraska, which aren’t prioritizing renewals by likely eligibility, about 90% have been renewed.

Because of the 3-year pause in renewals, many people on Medicaid have never been through the process or aren’t aware they may need to fill out long verification forms, as a recent KFF poll found. Some people moved and didn’t update their contact information.

And while agencies are required to assist enrollees who don’t speak English well, many are sending the forms in only a few common languages.

Tens of thousands of children are losing coverage, as researchers have warned, even though some may still qualify for Medicaid or CHIP. In its first month of reviews, South Dakota ended coverage for 10% of all Medicaid and CHIP enrollees in the state. More than half of them were children. In Arkansas, about 40% were kids.

Many parents don’t know that limits on household income are significantly higher for children than adults. Parents should fill out renewal forms even if they don’t qualify themselves, said Joan Alker, executive director of the Georgetown University Center for Children and Families, Washington.

New Hampshire has moved most families with children to the end of the review process. Mr. Lipman said his biggest worry is that a child will end up uninsured. Florida also planned to push kids with serious health conditions and other vulnerable groups to the end of the review line.

But according to Miriam Harmatz, advocacy director and founder of the Florida Health Justice Project, state officials sent cancellation letters to several clients with disabled children who probably still qualify. She’s helping those families appeal.

Nearly 250,000 Floridians reviewed in the first month of the unwinding lost coverage, 82% of them for reasons like incomplete paperwork, the state reported to federal authorities. House Democrats from the state petitioned Republican Gov. Ron DeSantis to pause the unwinding.

Advocacy coalitions in both Florida and Arkansas also have called for investigations into the review process and a pause on cancellations.

The state is contacting enrollees by phone, email, and text, and continues to process late applications, said Tori Cuddy, a spokesperson for the Florida Department of Children and Families. Ms. Cuddy did not respond to questions about issues raised in the petitions.

Federal officials are investigating those complaints and any other problems that emerge, said Dan Tsai, director of the Center for Medicaid & CHIP Services. “If we find that the rules are not being followed, we will take action.”

His agency has directed states to automatically reenroll residents using data from other government programs like unemployment and food assistance when possible. Anyone who can’t be approved through that process must act quickly.

“For the past 3 years, people have been told to ignore the mail around this, that the renewal was not going to lead to a termination.” Suddenly that mail matters, he said.

Federal law requires states to tell people why they’re losing Medicaid coverage and how to appeal the decision.

Ms. Harmatz said some cancellation notices in Florida are vague and could violate due process rules. Letters that she’s seen say “your Medicaid for this period is ending” rather than providing a specific reason for disenrollment, like having too high an income or incomplete paperwork.
If a person requests a hearing before their cancellation takes effect, they can stay covered during the appeals process. Even after being disenrolled, many still have a 90-day window to restore coverage.

In New Hampshire, 13% of people deemed ineligible in the first month have asked for extra time to provide the necessary records. “If you’re eligible for Medicaid, we don’t want you to lose it,” said Mr. Lipman.

Rep. Clere pushed Indiana’s Medicaid officials during the May meeting to immediately make changes to avoid people unnecessarily becoming uninsured. One official responded that they’ll learn and improve over time.

“I’m just concerned that we’re going to be ‘learning’ as a result of people losing coverage,” Rep. Clere replied. “So I don’t want to learn at their expense.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

CHICAGO – Sunscreen recommendations are most effective when a multitude of factors are considered, Susan C. Taylor, MD, said during a presentation on personal photoprotection at the inaugural Pigmentary Disorders Exchange Symposium.

Among the first factors physicians should consider before recommending sunscreen are a patient’s Fitzpatrick skin type, risks for burning or tanning, underlying skin disorders, and medications the patient is taking, Dr. Taylor, professor of dermatology at the University of Pennsylvania, Philadelphia, said at the meeting, provided by MedscapeLIVE! If patients are on hypertensives, for example, medications can make them more photosensitive.

MedscapeLIVE!

Consider skin type

Dr. Taylor said she was dismayed by the results of a recent study, which found that 43% of dermatologists who responded to a survey reported that they never, rarely, or only sometimes took a patient’s skin type into account when making sunscreen recommendations. The article is referenced in a 2022 expert panel consensus paper she coauthored on photoprotection “for skin of all color.” But she pointed out that considering skin type alone is inadequate.

Questions for patients in joint decision-making should include lifestyle and work choices such as whether they work inside or outside, and how much sun exposure they get in a typical day. Heat and humidity levels should also be considered as should a patient’s susceptibility to dyspigmentation. “That could be overall darkening of the skin, mottled hyperpigmentation, actinic dyspigmentation, and, of course, propensity for skin cancer,” she said.
 

Use differs by race

Dr. Taylor, who is also vice chair for diversity, equity and inclusion in the department of dermatology at the University of Pennsylvania, pointed out that sunscreen use differs considerably by race.

In study of 8,952 adults in the United States who reported that they were sun sensitive found that a subset of adults with skin of color were significantly less likely to use sunscreen when compared with non-Hispanic White adults: Non-Hispanic Black (adjusted odds ratio, 0.43); non-Hispanic Asian (aOR. 0.54); and Hispanic (aOR, 0.70) adults.

In the study, non-Hispanic Black and Hispanic adults were significantly less likely to use sunscreens with an SPF greater than 15. In addition, non-Hispanic Black, non-Hispanic Asian, and Hispanic adults were significantly more likely than non-Hispanic Whites to wear long sleeves when outside. Such differences are important to keep in mind when advising patients about sunscreens, she said.
 

Protection for lighter-colored skin

Dr. Taylor said that, for patients with lighter skin tones, “we really want to protect against ultraviolet B as well as ultraviolet A, particularly ultraviolet A2. Ultraviolet radiation is going to cause DNA damage.” Patients with Fitzpatrick skin types I, II, or III are most susceptible to the effects of UVB with sunburn inflammation, which will cause erythema and tanning, and immunosuppression.

“For those who are I, II, and III, we do want to recommend a broad-spectrum, photostable sunscreen with a critical wavelength of 370 nanometers, which is going to protect from both UVB and UVA2,” she said.

Sunscreen recommendations are meant to be paired with advice to avoid midday sun from 10 a.m. to 2 p.m., wearing protective clothing and accessories, and seeking shade, she noted.

Dr. Taylor said, for those patients with lighter skin who are more susceptible to photodamage and premature aging, physicians should recommend sunscreens that contain DNA repair enzymes such as photolyases and sunscreens that contain antioxidants that can prevent or reverse DNA damage. “The exogenous form of these lyases have been manufactured and added to sunscreens,” Dr. Taylor said. “They’re readily available in the United States. That is something to consider for patients with significant photodamage.”

Retinoids can also help alleviate or reverse photodamage, she added.
 

Protection for darker-colored skin

“Many people of color do not believe they need sunscreen,” Dr. Taylor said. But studies show that, although there may be more intrinsic protection, sunscreen is still needed.

Over 30 years ago, Halder and colleagues reported that melanin in skin of color can filter two to five times more UV radiation, and in a paper on the photoprotective role of melanin, Kaidbey and colleagues found that skin types V and VI had an intrinsic SPF of 13 when compared with those who have lighter complexions, which had an SPF of 3.

Sunburns seem to occur less frequently in people with skin of color, but that may be because erythema is less apparent in people with darker skin tones or because of differences in personal definitions of sunburn, Dr. Taylor said.

“Skin of color can and does sustain sunburns and sunscreen will help prevent that,” she said, adding that a recommendation of an SPF 30 is likely sufficient for these patients. Dr. Taylor noted that sunscreens for patients with darker skin often cost substantially more than those for lighter skin, and that should be considered in recommendations.

Tinted sunscreens

Dr. Taylor said that, while broad-spectrum photostable sunscreens protect against UVB and UVA 2, they don’t protect from visible light and UVA1. Two methods to add that protection are using inorganic tinted sunscreens that contain iron oxide or pigmentary titanium dioxide. Dr. Taylor was a coauthor of a practical guide to tinted sunscreens published in 2022.

“For iron oxide, we want a concentration of 3% or greater,” she said, adding that the percentage often is not known because if it is contained in a sunscreen, it is listed as an inactive ingredient.

Another method to address visible light and UVA1 is the use of antioxidant-containing sunscreens with vitamin E, vitamin C, or licochalcone A, Dr. Taylor said.

During the question-and-answer period following her presentation, Amit Pandya, MD, adjunct professor of dermatology at University of Texas Southwestern Medical Center, Dallas, asked why “every makeup, every sunscreen, just says iron oxide,” since it is known that visible light will cause pigmentation, especially in those with darker skin tones.

He urged pushing for a law that would require listing the percentage of iron oxide on products to assure it is sufficient, according to what the literature recommends.

Conference Chair Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute of Southern California, Los Angeles, said that she recommends tinted sunscreens almost exclusively for her patients, but those with darker skin colors struggle to match color.

Dr. Taylor referred to an analysis published in 2022 of 58 over-the counter sunscreens, which found that only 38% of tinted sunscreens was available in more than one shade, “which is a problem for many of our patients.” She said that providing samples with different hues and tactile sensations may help patients find the right product.

Dr. Taylor disclosed being on the advisory boards for AbbVie, Avita Medical, Beiersdorf, Biorez, Eli Lily, EPI Health, Evolus, Galderma, Hugel America, Johnson and Johnson, L’Oreal USA, MedScape, Pfizer, Scientis US, UCB, Vichy Laboratories. She is a consultant for Arcutis Biothermapeutics, Beiersdorf, Bristol-Myers Squibb, Cara Therapeutics, Dior, and Sanofi. She has done contracted research for Allergan Aesthetics, Concert Pharmaceuticals, Croma-Pharma, Eli Lilly, and Pfizer, and has an ownership interest in Armis Scientific, GloGetter, and Piction Health.

Medscape and this news organization are owned by the same parent company.

CHICAGO – Sunscreen recommendations are most effective when a multitude of factors are considered, Susan C. Taylor, MD, said during a presentation on personal photoprotection at the inaugural Pigmentary Disorders Exchange Symposium.

Among the first factors physicians should consider before recommending sunscreen are a patient’s Fitzpatrick skin type, risks for burning or tanning, underlying skin disorders, and medications the patient is taking, Dr. Taylor, professor of dermatology at the University of Pennsylvania, Philadelphia, said at the meeting, provided by MedscapeLIVE! If patients are on hypertensives, for example, medications can make them more photosensitive.

MedscapeLIVE!

Consider skin type

Dr. Taylor said she was dismayed by the results of a recent study, which found that 43% of dermatologists who responded to a survey reported that they never, rarely, or only sometimes took a patient’s skin type into account when making sunscreen recommendations. The article is referenced in a 2022 expert panel consensus paper she coauthored on photoprotection “for skin of all color.” But she pointed out that considering skin type alone is inadequate.

Questions for patients in joint decision-making should include lifestyle and work choices such as whether they work inside or outside, and how much sun exposure they get in a typical day. Heat and humidity levels should also be considered as should a patient’s susceptibility to dyspigmentation. “That could be overall darkening of the skin, mottled hyperpigmentation, actinic dyspigmentation, and, of course, propensity for skin cancer,” she said.
 

Use differs by race

Dr. Taylor, who is also vice chair for diversity, equity and inclusion in the department of dermatology at the University of Pennsylvania, pointed out that sunscreen use differs considerably by race.

In study of 8,952 adults in the United States who reported that they were sun sensitive found that a subset of adults with skin of color were significantly less likely to use sunscreen when compared with non-Hispanic White adults: Non-Hispanic Black (adjusted odds ratio, 0.43); non-Hispanic Asian (aOR. 0.54); and Hispanic (aOR, 0.70) adults.

In the study, non-Hispanic Black and Hispanic adults were significantly less likely to use sunscreens with an SPF greater than 15. In addition, non-Hispanic Black, non-Hispanic Asian, and Hispanic adults were significantly more likely than non-Hispanic Whites to wear long sleeves when outside. Such differences are important to keep in mind when advising patients about sunscreens, she said.
 

Protection for lighter-colored skin

Dr. Taylor said that, for patients with lighter skin tones, “we really want to protect against ultraviolet B as well as ultraviolet A, particularly ultraviolet A2. Ultraviolet radiation is going to cause DNA damage.” Patients with Fitzpatrick skin types I, II, or III are most susceptible to the effects of UVB with sunburn inflammation, which will cause erythema and tanning, and immunosuppression.

“For those who are I, II, and III, we do want to recommend a broad-spectrum, photostable sunscreen with a critical wavelength of 370 nanometers, which is going to protect from both UVB and UVA2,” she said.

Sunscreen recommendations are meant to be paired with advice to avoid midday sun from 10 a.m. to 2 p.m., wearing protective clothing and accessories, and seeking shade, she noted.

Dr. Taylor said, for those patients with lighter skin who are more susceptible to photodamage and premature aging, physicians should recommend sunscreens that contain DNA repair enzymes such as photolyases and sunscreens that contain antioxidants that can prevent or reverse DNA damage. “The exogenous form of these lyases have been manufactured and added to sunscreens,” Dr. Taylor said. “They’re readily available in the United States. That is something to consider for patients with significant photodamage.”

Retinoids can also help alleviate or reverse photodamage, she added.
 

Protection for darker-colored skin

“Many people of color do not believe they need sunscreen,” Dr. Taylor said. But studies show that, although there may be more intrinsic protection, sunscreen is still needed.

Over 30 years ago, Halder and colleagues reported that melanin in skin of color can filter two to five times more UV radiation, and in a paper on the photoprotective role of melanin, Kaidbey and colleagues found that skin types V and VI had an intrinsic SPF of 13 when compared with those who have lighter complexions, which had an SPF of 3.

Sunburns seem to occur less frequently in people with skin of color, but that may be because erythema is less apparent in people with darker skin tones or because of differences in personal definitions of sunburn, Dr. Taylor said.

“Skin of color can and does sustain sunburns and sunscreen will help prevent that,” she said, adding that a recommendation of an SPF 30 is likely sufficient for these patients. Dr. Taylor noted that sunscreens for patients with darker skin often cost substantially more than those for lighter skin, and that should be considered in recommendations.

Tinted sunscreens

Dr. Taylor said that, while broad-spectrum photostable sunscreens protect against UVB and UVA 2, they don’t protect from visible light and UVA1. Two methods to add that protection are using inorganic tinted sunscreens that contain iron oxide or pigmentary titanium dioxide. Dr. Taylor was a coauthor of a practical guide to tinted sunscreens published in 2022.

“For iron oxide, we want a concentration of 3% or greater,” she said, adding that the percentage often is not known because if it is contained in a sunscreen, it is listed as an inactive ingredient.

Another method to address visible light and UVA1 is the use of antioxidant-containing sunscreens with vitamin E, vitamin C, or licochalcone A, Dr. Taylor said.

During the question-and-answer period following her presentation, Amit Pandya, MD, adjunct professor of dermatology at University of Texas Southwestern Medical Center, Dallas, asked why “every makeup, every sunscreen, just says iron oxide,” since it is known that visible light will cause pigmentation, especially in those with darker skin tones.

He urged pushing for a law that would require listing the percentage of iron oxide on products to assure it is sufficient, according to what the literature recommends.

Conference Chair Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute of Southern California, Los Angeles, said that she recommends tinted sunscreens almost exclusively for her patients, but those with darker skin colors struggle to match color.

Dr. Taylor referred to an analysis published in 2022 of 58 over-the counter sunscreens, which found that only 38% of tinted sunscreens was available in more than one shade, “which is a problem for many of our patients.” She said that providing samples with different hues and tactile sensations may help patients find the right product.

Dr. Taylor disclosed being on the advisory boards for AbbVie, Avita Medical, Beiersdorf, Biorez, Eli Lily, EPI Health, Evolus, Galderma, Hugel America, Johnson and Johnson, L’Oreal USA, MedScape, Pfizer, Scientis US, UCB, Vichy Laboratories. She is a consultant for Arcutis Biothermapeutics, Beiersdorf, Bristol-Myers Squibb, Cara Therapeutics, Dior, and Sanofi. She has done contracted research for Allergan Aesthetics, Concert Pharmaceuticals, Croma-Pharma, Eli Lilly, and Pfizer, and has an ownership interest in Armis Scientific, GloGetter, and Piction Health.

Medscape and this news organization are owned by the same parent company.

CHICAGO – Sunscreen recommendations are most effective when a multitude of factors are considered, Susan C. Taylor, MD, said during a presentation on personal photoprotection at the inaugural Pigmentary Disorders Exchange Symposium.

Among the first factors physicians should consider before recommending sunscreen are a patient’s Fitzpatrick skin type, risks for burning or tanning, underlying skin disorders, and medications the patient is taking, Dr. Taylor, professor of dermatology at the University of Pennsylvania, Philadelphia, said at the meeting, provided by MedscapeLIVE! If patients are on hypertensives, for example, medications can make them more photosensitive.

MedscapeLIVE!

Consider skin type

Dr. Taylor said she was dismayed by the results of a recent study, which found that 43% of dermatologists who responded to a survey reported that they never, rarely, or only sometimes took a patient’s skin type into account when making sunscreen recommendations. The article is referenced in a 2022 expert panel consensus paper she coauthored on photoprotection “for skin of all color.” But she pointed out that considering skin type alone is inadequate.

Questions for patients in joint decision-making should include lifestyle and work choices such as whether they work inside or outside, and how much sun exposure they get in a typical day. Heat and humidity levels should also be considered as should a patient’s susceptibility to dyspigmentation. “That could be overall darkening of the skin, mottled hyperpigmentation, actinic dyspigmentation, and, of course, propensity for skin cancer,” she said.
 

Use differs by race

Dr. Taylor, who is also vice chair for diversity, equity and inclusion in the department of dermatology at the University of Pennsylvania, pointed out that sunscreen use differs considerably by race.

In study of 8,952 adults in the United States who reported that they were sun sensitive found that a subset of adults with skin of color were significantly less likely to use sunscreen when compared with non-Hispanic White adults: Non-Hispanic Black (adjusted odds ratio, 0.43); non-Hispanic Asian (aOR. 0.54); and Hispanic (aOR, 0.70) adults.

In the study, non-Hispanic Black and Hispanic adults were significantly less likely to use sunscreens with an SPF greater than 15. In addition, non-Hispanic Black, non-Hispanic Asian, and Hispanic adults were significantly more likely than non-Hispanic Whites to wear long sleeves when outside. Such differences are important to keep in mind when advising patients about sunscreens, she said.
 

Protection for lighter-colored skin

Dr. Taylor said that, for patients with lighter skin tones, “we really want to protect against ultraviolet B as well as ultraviolet A, particularly ultraviolet A2. Ultraviolet radiation is going to cause DNA damage.” Patients with Fitzpatrick skin types I, II, or III are most susceptible to the effects of UVB with sunburn inflammation, which will cause erythema and tanning, and immunosuppression.

“For those who are I, II, and III, we do want to recommend a broad-spectrum, photostable sunscreen with a critical wavelength of 370 nanometers, which is going to protect from both UVB and UVA2,” she said.

Sunscreen recommendations are meant to be paired with advice to avoid midday sun from 10 a.m. to 2 p.m., wearing protective clothing and accessories, and seeking shade, she noted.

Dr. Taylor said, for those patients with lighter skin who are more susceptible to photodamage and premature aging, physicians should recommend sunscreens that contain DNA repair enzymes such as photolyases and sunscreens that contain antioxidants that can prevent or reverse DNA damage. “The exogenous form of these lyases have been manufactured and added to sunscreens,” Dr. Taylor said. “They’re readily available in the United States. That is something to consider for patients with significant photodamage.”

Retinoids can also help alleviate or reverse photodamage, she added.
 

Protection for darker-colored skin

“Many people of color do not believe they need sunscreen,” Dr. Taylor said. But studies show that, although there may be more intrinsic protection, sunscreen is still needed.

Over 30 years ago, Halder and colleagues reported that melanin in skin of color can filter two to five times more UV radiation, and in a paper on the photoprotective role of melanin, Kaidbey and colleagues found that skin types V and VI had an intrinsic SPF of 13 when compared with those who have lighter complexions, which had an SPF of 3.

Sunburns seem to occur less frequently in people with skin of color, but that may be because erythema is less apparent in people with darker skin tones or because of differences in personal definitions of sunburn, Dr. Taylor said.

“Skin of color can and does sustain sunburns and sunscreen will help prevent that,” she said, adding that a recommendation of an SPF 30 is likely sufficient for these patients. Dr. Taylor noted that sunscreens for patients with darker skin often cost substantially more than those for lighter skin, and that should be considered in recommendations.

Tinted sunscreens

Dr. Taylor said that, while broad-spectrum photostable sunscreens protect against UVB and UVA 2, they don’t protect from visible light and UVA1. Two methods to add that protection are using inorganic tinted sunscreens that contain iron oxide or pigmentary titanium dioxide. Dr. Taylor was a coauthor of a practical guide to tinted sunscreens published in 2022.

“For iron oxide, we want a concentration of 3% or greater,” she said, adding that the percentage often is not known because if it is contained in a sunscreen, it is listed as an inactive ingredient.

Another method to address visible light and UVA1 is the use of antioxidant-containing sunscreens with vitamin E, vitamin C, or licochalcone A, Dr. Taylor said.

During the question-and-answer period following her presentation, Amit Pandya, MD, adjunct professor of dermatology at University of Texas Southwestern Medical Center, Dallas, asked why “every makeup, every sunscreen, just says iron oxide,” since it is known that visible light will cause pigmentation, especially in those with darker skin tones.

He urged pushing for a law that would require listing the percentage of iron oxide on products to assure it is sufficient, according to what the literature recommends.

Conference Chair Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute of Southern California, Los Angeles, said that she recommends tinted sunscreens almost exclusively for her patients, but those with darker skin colors struggle to match color.

Dr. Taylor referred to an analysis published in 2022 of 58 over-the counter sunscreens, which found that only 38% of tinted sunscreens was available in more than one shade, “which is a problem for many of our patients.” She said that providing samples with different hues and tactile sensations may help patients find the right product.

Dr. Taylor disclosed being on the advisory boards for AbbVie, Avita Medical, Beiersdorf, Biorez, Eli Lily, EPI Health, Evolus, Galderma, Hugel America, Johnson and Johnson, L’Oreal USA, MedScape, Pfizer, Scientis US, UCB, Vichy Laboratories. She is a consultant for Arcutis Biothermapeutics, Beiersdorf, Bristol-Myers Squibb, Cara Therapeutics, Dior, and Sanofi. She has done contracted research for Allergan Aesthetics, Concert Pharmaceuticals, Croma-Pharma, Eli Lilly, and Pfizer, and has an ownership interest in Armis Scientific, GloGetter, and Piction Health.

Medscape and this news organization are owned by the same parent company.

MILAN – Results of a phase 3 trial with the investigational drug telitacicept show that patients with systemic lupus erythematosus have a significantly greater rate of response to SLE response criteria, compared with placebo, while results from a phase 2 trial of the drug in patients with primary Sjögren’s syndrome (pSS) also show significant improvements versus placebo.

“With only a limited number of treatments available for patients with lupus, this additional option is certainly an advance and the trial shows a strong efficacy result,” said Ronald van Vollenhoven, MD, PhD, who was not an investigator for either trial but presented the results for both at the annual European Congress of Rheumatology. He is professor of clinical immunology and rheumatology at Amsterdam University Medical Center and VU University Medical Center, also in Amsterdam.

Becky McCall/MDedge News

Telitacicept is a recombinant fusion protein that targets B-lymphocyte stimulator and a proliferating-inducing ligand. It is currently undergoing testing in another phase 3 trial (REMESLE-1) at sites in the United States, Europe, and Asia. The current SLE results relate to the phase 3 study conducted in China, Dr. van Vollenhoven clarified.
 

SLE trial

The double-blind, placebo-controlled trial included 335 patients with SLE who had an average age of 35 years, a body mass index of 22-23 kg/m², and a mean SELENA-SLEDAI (Safety of Estrogens in Systemic Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index) score of at least 11.5, indicating high disease activity. Most patients were on glucocorticoids and immunosuppressants.

Patients were randomized 1:1 to weekly subcutaneous injections of telitacicept (160 mg; n = 167) or placebo (n = 168) in combination with standard therapy for 52 weeks. The primary endpoint was the SLE Responder Index-4 (SRI4) response rate at week 52, while key secondary endpoints included SELENA-SLEDAI, physician global assessment, and levels of immunologic biomarkers including C3, C4, IgM, IgG, IgA, and CD19+ B cells. Safety was also assessed.

At week 52, Dr. van Vollenhoven reported that significantly more patients taking telitacicept achieved a SRI4 response, compared with placebo, at 67.1% versus 32.7%, respectively (P < .001). “The difference was seen at 4-8 weeks and stabilized at around 20 weeks,” he said.

Time to first SLE flare was also reduced in patients on the trial drug at a median of 198 days (95% confidence interval, 169-254 days), compared with placebo at 115 days (95% CI, 92-140 days).

“The secondary outcomes also supported efficacy in these patients,” Dr. van Vollenhoven added, noting that there was a rapid and sustained increase of C3 and C4, the latter being significantly greater than placebo, and reduction of IgM, IgG, IgA, and CD19+ B cells observed following telitacicept treatment.

A significantly higher proportion of patients in the telitacicept group showed improvement in SELENA-SLEDAI at week 52, defined as a 4-point or greater reduction, compared with placebo (70.1% vs. 40.5%).

Telitacicept did not increase the risk of infections. Treatment-emergent adverse events occurred in 84.5% with telitacicept versus 91.6% with placebo, with infections (mostly upper respiratory) seen in 65.3% and 60.1%, respectively.
 

Sjögren’s trial

The second trial was a phase 2, randomized, placebo-controlled, 24-week study in 42 patients with pSS. Patients (18-65 years) received telitacicept at 160 mg or 240 mg subcutaneously once a week, or placebo, for a total of 24 doses. Patients had a EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score of 5 points or more, and were anti-SSA antibody positive.

“Compared with placebo, telitacicept treatment resulted in significant improvement in ESSDAI and MFI-20 [20-item Multidimensional Fatigue Inventory],” Dr. van Vollenhoven reported, adding that, “there was a trend for improvement in salivary gland function and lacrimal gland function relative to placebo, as well as a favorable safety profile.”

ESSDAI change from baseline was 0.5, –3.8, and –2.3 in placebo, 160-mg, and 240-mg telitacicept doses, respectively. MFI-20 change from baseline was 7.0, –4.0, and –5.1, respectively. Dr. Van Vollenhoven said the difference between the doses was not statistically significant.

“If these results are confirmed, it could be the first time a biologic is proven efficacious in this disease,” Dr. Van Vollenhoven said in an interview. “It’s encouraging to know that a new treatment is showing promise in this phase 2 trial. A phase 3 trial is warranted.”
 

Studies yield promising but confusing results

In an interview, Roy Fleischmann, MD, who was not involved with either study, wondered whether the results of the SLE study could be race specific given the magnitude of response to the drug and that the trial was conducted only in China, and whether the positive results of the small Sjögren’s study will pan out in a larger trial.

“The SLE study was very interesting, but the problem is that it’s a Chinese drug in Chinese patients with Chinese doctors, so they are very dramatic results,” he said, questioning whether “these results are race specific,” and that “we will find out when they do the multinational study, but we haven’t seen this type of separation before [in response]. It’s interesting.

“The Sjögren’s was a positive study, but it was confusing because the low dose seemed to be better than the higher dose, and there were very few patients,” said Dr. Fleischmann, clinical professor of medicine at the University of Texas Southwestern Medical Center and codirector of the Metroplex Clinical Research Center, both in Dallas. The left and right eyes gave different results, which was strange, and the salivary gland test was the same [mixed results], so what can we conclude? All in all, it was a small study with a suggestion of efficacy, but we have to do the phase 3 and see what it shows.”

Both trials were sponsored by RemeGen. Dr. van Vollenhoven reported serving as a paid adviser to AbbVie, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Pfizer, RemeGen, and UCB. He has received research funding from Bristol-Myers Squibb and UCB and educational support from AstraZeneca, Galapagos, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Fleischmann said he had has no relevant financial relationships.

MILAN – Results of a phase 3 trial with the investigational drug telitacicept show that patients with systemic lupus erythematosus have a significantly greater rate of response to SLE response criteria, compared with placebo, while results from a phase 2 trial of the drug in patients with primary Sjögren’s syndrome (pSS) also show significant improvements versus placebo.

“With only a limited number of treatments available for patients with lupus, this additional option is certainly an advance and the trial shows a strong efficacy result,” said Ronald van Vollenhoven, MD, PhD, who was not an investigator for either trial but presented the results for both at the annual European Congress of Rheumatology. He is professor of clinical immunology and rheumatology at Amsterdam University Medical Center and VU University Medical Center, also in Amsterdam.

Becky McCall/MDedge News

Telitacicept is a recombinant fusion protein that targets B-lymphocyte stimulator and a proliferating-inducing ligand. It is currently undergoing testing in another phase 3 trial (REMESLE-1) at sites in the United States, Europe, and Asia. The current SLE results relate to the phase 3 study conducted in China, Dr. van Vollenhoven clarified.
 

SLE trial

The double-blind, placebo-controlled trial included 335 patients with SLE who had an average age of 35 years, a body mass index of 22-23 kg/m², and a mean SELENA-SLEDAI (Safety of Estrogens in Systemic Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index) score of at least 11.5, indicating high disease activity. Most patients were on glucocorticoids and immunosuppressants.

Patients were randomized 1:1 to weekly subcutaneous injections of telitacicept (160 mg; n = 167) or placebo (n = 168) in combination with standard therapy for 52 weeks. The primary endpoint was the SLE Responder Index-4 (SRI4) response rate at week 52, while key secondary endpoints included SELENA-SLEDAI, physician global assessment, and levels of immunologic biomarkers including C3, C4, IgM, IgG, IgA, and CD19+ B cells. Safety was also assessed.

At week 52, Dr. van Vollenhoven reported that significantly more patients taking telitacicept achieved a SRI4 response, compared with placebo, at 67.1% versus 32.7%, respectively (P < .001). “The difference was seen at 4-8 weeks and stabilized at around 20 weeks,” he said.

Time to first SLE flare was also reduced in patients on the trial drug at a median of 198 days (95% confidence interval, 169-254 days), compared with placebo at 115 days (95% CI, 92-140 days).

“The secondary outcomes also supported efficacy in these patients,” Dr. van Vollenhoven added, noting that there was a rapid and sustained increase of C3 and C4, the latter being significantly greater than placebo, and reduction of IgM, IgG, IgA, and CD19+ B cells observed following telitacicept treatment.

A significantly higher proportion of patients in the telitacicept group showed improvement in SELENA-SLEDAI at week 52, defined as a 4-point or greater reduction, compared with placebo (70.1% vs. 40.5%).

Telitacicept did not increase the risk of infections. Treatment-emergent adverse events occurred in 84.5% with telitacicept versus 91.6% with placebo, with infections (mostly upper respiratory) seen in 65.3% and 60.1%, respectively.
 

Sjögren’s trial

The second trial was a phase 2, randomized, placebo-controlled, 24-week study in 42 patients with pSS. Patients (18-65 years) received telitacicept at 160 mg or 240 mg subcutaneously once a week, or placebo, for a total of 24 doses. Patients had a EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score of 5 points or more, and were anti-SSA antibody positive.

“Compared with placebo, telitacicept treatment resulted in significant improvement in ESSDAI and MFI-20 [20-item Multidimensional Fatigue Inventory],” Dr. van Vollenhoven reported, adding that, “there was a trend for improvement in salivary gland function and lacrimal gland function relative to placebo, as well as a favorable safety profile.”

ESSDAI change from baseline was 0.5, –3.8, and –2.3 in placebo, 160-mg, and 240-mg telitacicept doses, respectively. MFI-20 change from baseline was 7.0, –4.0, and –5.1, respectively. Dr. Van Vollenhoven said the difference between the doses was not statistically significant.

“If these results are confirmed, it could be the first time a biologic is proven efficacious in this disease,” Dr. Van Vollenhoven said in an interview. “It’s encouraging to know that a new treatment is showing promise in this phase 2 trial. A phase 3 trial is warranted.”
 

Studies yield promising but confusing results

In an interview, Roy Fleischmann, MD, who was not involved with either study, wondered whether the results of the SLE study could be race specific given the magnitude of response to the drug and that the trial was conducted only in China, and whether the positive results of the small Sjögren’s study will pan out in a larger trial.

“The SLE study was very interesting, but the problem is that it’s a Chinese drug in Chinese patients with Chinese doctors, so they are very dramatic results,” he said, questioning whether “these results are race specific,” and that “we will find out when they do the multinational study, but we haven’t seen this type of separation before [in response]. It’s interesting.

“The Sjögren’s was a positive study, but it was confusing because the low dose seemed to be better than the higher dose, and there were very few patients,” said Dr. Fleischmann, clinical professor of medicine at the University of Texas Southwestern Medical Center and codirector of the Metroplex Clinical Research Center, both in Dallas. The left and right eyes gave different results, which was strange, and the salivary gland test was the same [mixed results], so what can we conclude? All in all, it was a small study with a suggestion of efficacy, but we have to do the phase 3 and see what it shows.”

Both trials were sponsored by RemeGen. Dr. van Vollenhoven reported serving as a paid adviser to AbbVie, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Pfizer, RemeGen, and UCB. He has received research funding from Bristol-Myers Squibb and UCB and educational support from AstraZeneca, Galapagos, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Fleischmann said he had has no relevant financial relationships.

MILAN – Results of a phase 3 trial with the investigational drug telitacicept show that patients with systemic lupus erythematosus have a significantly greater rate of response to SLE response criteria, compared with placebo, while results from a phase 2 trial of the drug in patients with primary Sjögren’s syndrome (pSS) also show significant improvements versus placebo.

“With only a limited number of treatments available for patients with lupus, this additional option is certainly an advance and the trial shows a strong efficacy result,” said Ronald van Vollenhoven, MD, PhD, who was not an investigator for either trial but presented the results for both at the annual European Congress of Rheumatology. He is professor of clinical immunology and rheumatology at Amsterdam University Medical Center and VU University Medical Center, also in Amsterdam.

Becky McCall/MDedge News

Telitacicept is a recombinant fusion protein that targets B-lymphocyte stimulator and a proliferating-inducing ligand. It is currently undergoing testing in another phase 3 trial (REMESLE-1) at sites in the United States, Europe, and Asia. The current SLE results relate to the phase 3 study conducted in China, Dr. van Vollenhoven clarified.
 

SLE trial

The double-blind, placebo-controlled trial included 335 patients with SLE who had an average age of 35 years, a body mass index of 22-23 kg/m², and a mean SELENA-SLEDAI (Safety of Estrogens in Systemic Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index) score of at least 11.5, indicating high disease activity. Most patients were on glucocorticoids and immunosuppressants.

Patients were randomized 1:1 to weekly subcutaneous injections of telitacicept (160 mg; n = 167) or placebo (n = 168) in combination with standard therapy for 52 weeks. The primary endpoint was the SLE Responder Index-4 (SRI4) response rate at week 52, while key secondary endpoints included SELENA-SLEDAI, physician global assessment, and levels of immunologic biomarkers including C3, C4, IgM, IgG, IgA, and CD19+ B cells. Safety was also assessed.

At week 52, Dr. van Vollenhoven reported that significantly more patients taking telitacicept achieved a SRI4 response, compared with placebo, at 67.1% versus 32.7%, respectively (P < .001). “The difference was seen at 4-8 weeks and stabilized at around 20 weeks,” he said.

Time to first SLE flare was also reduced in patients on the trial drug at a median of 198 days (95% confidence interval, 169-254 days), compared with placebo at 115 days (95% CI, 92-140 days).

“The secondary outcomes also supported efficacy in these patients,” Dr. van Vollenhoven added, noting that there was a rapid and sustained increase of C3 and C4, the latter being significantly greater than placebo, and reduction of IgM, IgG, IgA, and CD19+ B cells observed following telitacicept treatment.

A significantly higher proportion of patients in the telitacicept group showed improvement in SELENA-SLEDAI at week 52, defined as a 4-point or greater reduction, compared with placebo (70.1% vs. 40.5%).

Telitacicept did not increase the risk of infections. Treatment-emergent adverse events occurred in 84.5% with telitacicept versus 91.6% with placebo, with infections (mostly upper respiratory) seen in 65.3% and 60.1%, respectively.
 

Sjögren’s trial

The second trial was a phase 2, randomized, placebo-controlled, 24-week study in 42 patients with pSS. Patients (18-65 years) received telitacicept at 160 mg or 240 mg subcutaneously once a week, or placebo, for a total of 24 doses. Patients had a EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score of 5 points or more, and were anti-SSA antibody positive.

“Compared with placebo, telitacicept treatment resulted in significant improvement in ESSDAI and MFI-20 [20-item Multidimensional Fatigue Inventory],” Dr. van Vollenhoven reported, adding that, “there was a trend for improvement in salivary gland function and lacrimal gland function relative to placebo, as well as a favorable safety profile.”

ESSDAI change from baseline was 0.5, –3.8, and –2.3 in placebo, 160-mg, and 240-mg telitacicept doses, respectively. MFI-20 change from baseline was 7.0, –4.0, and –5.1, respectively. Dr. Van Vollenhoven said the difference between the doses was not statistically significant.

“If these results are confirmed, it could be the first time a biologic is proven efficacious in this disease,” Dr. Van Vollenhoven said in an interview. “It’s encouraging to know that a new treatment is showing promise in this phase 2 trial. A phase 3 trial is warranted.”
 

Studies yield promising but confusing results

In an interview, Roy Fleischmann, MD, who was not involved with either study, wondered whether the results of the SLE study could be race specific given the magnitude of response to the drug and that the trial was conducted only in China, and whether the positive results of the small Sjögren’s study will pan out in a larger trial.

“The SLE study was very interesting, but the problem is that it’s a Chinese drug in Chinese patients with Chinese doctors, so they are very dramatic results,” he said, questioning whether “these results are race specific,” and that “we will find out when they do the multinational study, but we haven’t seen this type of separation before [in response]. It’s interesting.

“The Sjögren’s was a positive study, but it was confusing because the low dose seemed to be better than the higher dose, and there were very few patients,” said Dr. Fleischmann, clinical professor of medicine at the University of Texas Southwestern Medical Center and codirector of the Metroplex Clinical Research Center, both in Dallas. The left and right eyes gave different results, which was strange, and the salivary gland test was the same [mixed results], so what can we conclude? All in all, it was a small study with a suggestion of efficacy, but we have to do the phase 3 and see what it shows.”

Both trials were sponsored by RemeGen. Dr. van Vollenhoven reported serving as a paid adviser to AbbVie, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Pfizer, RemeGen, and UCB. He has received research funding from Bristol-Myers Squibb and UCB and educational support from AstraZeneca, Galapagos, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Fleischmann said he had has no relevant financial relationships.

A team of researchers has identified genomic variants that cause disabling pansclerotic morphea (DPM), a rare, severe inflammatory skin disorder, and report that the Janus kinase (JAK) inhibitor ruxolitinib may be a useful therapy, especially in patients who have not responded to other interventions.

DPM was first reported in 1923, and while a genetic cause has been suspected, it had not been identified until now. The disease is the most severe form of deep morphea, which affects individuals with juvenile localized scleroderma. Patients, generally children under age 14, experience rapid sclerosis of all layers of the skin, fascia, muscle, and bone. DPM is also deadly: Most patients do not live more than 10 years after diagnosis, as they contract squamous cell carcinoma, restrictive pulmonary disease, sepsis, and gangrene.

In the study, published in the New England Journal of Medicine, the researchers discovered that people with DPM have an overactive version of the protein STAT4, which regulates inflammation and wound healing. The scientists studied four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM.

“Researchers previously thought that this disorder was caused by the immune system attacking the skin,” Sarah Blackstone, a predoctoral fellow in the inflammatory disease section at the National Human Genome Research Institute and co–first author of the study, said in a statement from the National Institutes of Health describing the results. “However, we found that this is an oversimplification, and that both skin and the immune system play an active role in disabling pansclerotic morphea,” added Ms. Blackstone, also a medical student at the University of South Dakota, Sioux Falls.

The overactive STAT4 protein creates a positive feedback loop of inflammation and impaired wound-healing. By targeting JAK, the researchers were able to stop the feedback and patients’ wounds dramatically improved. After 18 months of treatment with oral ruxolitinib, one patient had discontinued all other medications, and had complete resolution of a chest rash, substantial clearing on the arms and legs, and global clinical improvement.

The authors said that oral systemic JAK inhibitor therapy is preferred over topical therapy. Their research also suggested that anti–interleukin-6 monoclonal antibodies – such as tocilizumab, approved for indications that include rheumatoid arthritis and systemic sclerosis–associated interstitial lung disease, “may be an alternative therapy or may be useful in combination with JAK inhibitors in patients with DPM,” the authors wrote.

Most current DPM therapies – including methotrexate, mycophenolate mofetil, and ultraviolet A light therapy – have been ineffective, and some have severe side effects.

“The findings of this study open doors for JAK inhibitors to be a potential treatment for other inflammatory skin disorders or disorders related to tissue scarring, whether it is scarring of the lungs, liver or bone marrow,” Dan Kastner, MD, PhD, an NIH distinguished investigator, head of the NHGRI’s inflammatory disease section, and a senior author of the paper, said in the NIH statement.

“We hope to continue studying other molecules in this pathway and how they are altered in patients with disabling pansclerotic morphea and related conditions to find clues to understanding a broader array of more common diseases,” Lori Broderick, MD, PhD, a senior author of the paper and an associate professor at University of California, San Diego, said in the statement.

The study was led by researchers at NHGRI in collaboration with researchers from UCSD and the University of Pittsburgh. Researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases also participated.

The study was supported by grants from the American Academy of Allergy, Asthma, and Immunology Foundation; the Ludwig Institute for Cancer Research; the University of California, San Diego, department of pediatrics; and the Novo Nordisk Foundation. Additional support and grants were given by the Deutsche Forschungsgemeinschaft, various institutes at the NIH, the California Institute for Regenerative Medicine, the Hydrocephalus Association, the Scleroderma Research Foundation, the Biowulf High-Performance Computing Cluster of the Center for Information Technology, the Undiagnosed Diseases Program of the Common Fund of the Office of the Director of the NIH, and the NIH Clinical Center.

A team of researchers has identified genomic variants that cause disabling pansclerotic morphea (DPM), a rare, severe inflammatory skin disorder, and report that the Janus kinase (JAK) inhibitor ruxolitinib may be a useful therapy, especially in patients who have not responded to other interventions.

DPM was first reported in 1923, and while a genetic cause has been suspected, it had not been identified until now. The disease is the most severe form of deep morphea, which affects individuals with juvenile localized scleroderma. Patients, generally children under age 14, experience rapid sclerosis of all layers of the skin, fascia, muscle, and bone. DPM is also deadly: Most patients do not live more than 10 years after diagnosis, as they contract squamous cell carcinoma, restrictive pulmonary disease, sepsis, and gangrene.

In the study, published in the New England Journal of Medicine, the researchers discovered that people with DPM have an overactive version of the protein STAT4, which regulates inflammation and wound healing. The scientists studied four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM.

“Researchers previously thought that this disorder was caused by the immune system attacking the skin,” Sarah Blackstone, a predoctoral fellow in the inflammatory disease section at the National Human Genome Research Institute and co–first author of the study, said in a statement from the National Institutes of Health describing the results. “However, we found that this is an oversimplification, and that both skin and the immune system play an active role in disabling pansclerotic morphea,” added Ms. Blackstone, also a medical student at the University of South Dakota, Sioux Falls.

The overactive STAT4 protein creates a positive feedback loop of inflammation and impaired wound-healing. By targeting JAK, the researchers were able to stop the feedback and patients’ wounds dramatically improved. After 18 months of treatment with oral ruxolitinib, one patient had discontinued all other medications, and had complete resolution of a chest rash, substantial clearing on the arms and legs, and global clinical improvement.

The authors said that oral systemic JAK inhibitor therapy is preferred over topical therapy. Their research also suggested that anti–interleukin-6 monoclonal antibodies – such as tocilizumab, approved for indications that include rheumatoid arthritis and systemic sclerosis–associated interstitial lung disease, “may be an alternative therapy or may be useful in combination with JAK inhibitors in patients with DPM,” the authors wrote.

Most current DPM therapies – including methotrexate, mycophenolate mofetil, and ultraviolet A light therapy – have been ineffective, and some have severe side effects.

“The findings of this study open doors for JAK inhibitors to be a potential treatment for other inflammatory skin disorders or disorders related to tissue scarring, whether it is scarring of the lungs, liver or bone marrow,” Dan Kastner, MD, PhD, an NIH distinguished investigator, head of the NHGRI’s inflammatory disease section, and a senior author of the paper, said in the NIH statement.

“We hope to continue studying other molecules in this pathway and how they are altered in patients with disabling pansclerotic morphea and related conditions to find clues to understanding a broader array of more common diseases,” Lori Broderick, MD, PhD, a senior author of the paper and an associate professor at University of California, San Diego, said in the statement.

The study was led by researchers at NHGRI in collaboration with researchers from UCSD and the University of Pittsburgh. Researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases also participated.

The study was supported by grants from the American Academy of Allergy, Asthma, and Immunology Foundation; the Ludwig Institute for Cancer Research; the University of California, San Diego, department of pediatrics; and the Novo Nordisk Foundation. Additional support and grants were given by the Deutsche Forschungsgemeinschaft, various institutes at the NIH, the California Institute for Regenerative Medicine, the Hydrocephalus Association, the Scleroderma Research Foundation, the Biowulf High-Performance Computing Cluster of the Center for Information Technology, the Undiagnosed Diseases Program of the Common Fund of the Office of the Director of the NIH, and the NIH Clinical Center.

A team of researchers has identified genomic variants that cause disabling pansclerotic morphea (DPM), a rare, severe inflammatory skin disorder, and report that the Janus kinase (JAK) inhibitor ruxolitinib may be a useful therapy, especially in patients who have not responded to other interventions.

DPM was first reported in 1923, and while a genetic cause has been suspected, it had not been identified until now. The disease is the most severe form of deep morphea, which affects individuals with juvenile localized scleroderma. Patients, generally children under age 14, experience rapid sclerosis of all layers of the skin, fascia, muscle, and bone. DPM is also deadly: Most patients do not live more than 10 years after diagnosis, as they contract squamous cell carcinoma, restrictive pulmonary disease, sepsis, and gangrene.

In the study, published in the New England Journal of Medicine, the researchers discovered that people with DPM have an overactive version of the protein STAT4, which regulates inflammation and wound healing. The scientists studied four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM.

“Researchers previously thought that this disorder was caused by the immune system attacking the skin,” Sarah Blackstone, a predoctoral fellow in the inflammatory disease section at the National Human Genome Research Institute and co–first author of the study, said in a statement from the National Institutes of Health describing the results. “However, we found that this is an oversimplification, and that both skin and the immune system play an active role in disabling pansclerotic morphea,” added Ms. Blackstone, also a medical student at the University of South Dakota, Sioux Falls.

The overactive STAT4 protein creates a positive feedback loop of inflammation and impaired wound-healing. By targeting JAK, the researchers were able to stop the feedback and patients’ wounds dramatically improved. After 18 months of treatment with oral ruxolitinib, one patient had discontinued all other medications, and had complete resolution of a chest rash, substantial clearing on the arms and legs, and global clinical improvement.

The authors said that oral systemic JAK inhibitor therapy is preferred over topical therapy. Their research also suggested that anti–interleukin-6 monoclonal antibodies – such as tocilizumab, approved for indications that include rheumatoid arthritis and systemic sclerosis–associated interstitial lung disease, “may be an alternative therapy or may be useful in combination with JAK inhibitors in patients with DPM,” the authors wrote.

Most current DPM therapies – including methotrexate, mycophenolate mofetil, and ultraviolet A light therapy – have been ineffective, and some have severe side effects.

“The findings of this study open doors for JAK inhibitors to be a potential treatment for other inflammatory skin disorders or disorders related to tissue scarring, whether it is scarring of the lungs, liver or bone marrow,” Dan Kastner, MD, PhD, an NIH distinguished investigator, head of the NHGRI’s inflammatory disease section, and a senior author of the paper, said in the NIH statement.

“We hope to continue studying other molecules in this pathway and how they are altered in patients with disabling pansclerotic morphea and related conditions to find clues to understanding a broader array of more common diseases,” Lori Broderick, MD, PhD, a senior author of the paper and an associate professor at University of California, San Diego, said in the statement.

The study was led by researchers at NHGRI in collaboration with researchers from UCSD and the University of Pittsburgh. Researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases also participated.

The study was supported by grants from the American Academy of Allergy, Asthma, and Immunology Foundation; the Ludwig Institute for Cancer Research; the University of California, San Diego, department of pediatrics; and the Novo Nordisk Foundation. Additional support and grants were given by the Deutsche Forschungsgemeinschaft, various institutes at the NIH, the California Institute for Regenerative Medicine, the Hydrocephalus Association, the Scleroderma Research Foundation, the Biowulf High-Performance Computing Cluster of the Center for Information Technology, the Undiagnosed Diseases Program of the Common Fund of the Office of the Director of the NIH, and the NIH Clinical Center.

Around 5% of patients treated with dupilumab (Dupixent) for moderate-to-severe atopic dermatitis experience musculoskeletal (MSK) symptoms, according to the results of a descriptive study.

The main MSK symptom seen in the observational cohort was enthesitis, but some patients also experienced arthritis and tenosynovitis a median of 17 weeks after starting dupilumab treatment. Together these symptoms represent a new MSK syndrome, say researchers from the United Kingdom.

“The pattern of MSK symptoms and signs is characteristic of psoriatic arthritis/peripheral spondyloarthritis,” Bruce Kirkham, MD, and collaborators report in Arthritis & Rheumatology.

“We started a few years ago and have been following the patients for quite a long time,” Dr. Kirkham, a consultant rheumatologist at Guy’s and St. Thomas’ NHS Foundation Trust, London, told this news organization.

Characterizing the MSK symptoms

Of 470 patients with atopic dermatitis who started treatment with dupilumab at Guy’s and St. Thomas’ NHS Foundation Trust between October 2018 and February 2021, 36 (7.65%) developed rheumatic symptoms and were referred to the rheumatology department. These individuals had their family history assessed and thorough MSK evaluations, which included antibody and inflammatory markers, ultrasound of the peripheral small joints, and MRI of the large joints and spine.

A total of 26 (5.5%) patients – 14 of whom were male – had inflammatory enthesitis, arthritis, and/or tenosynovitis. Of the others, seven had osteoarthritis and three had degenerative spine disease.

Enthesitis was the most common finding in those with rheumatic symptoms, occurring on its own in 11 patients, with arthritis in three patients, and tenosynovitis in two patients.  

These symptoms appeared 2-48 weeks after starting dupilumab treatment and were categorized as mild in 16 (61%) cases, moderate in six cases, and severe in four cases.

No specific predictors of the MSK symptoms seen were noted. Patient age, sex, duration of their atopic dermatitis, or how their skin condition had been previously treated did not help identify those who might develop rheumatic problems.
 

Conservative management approach

All patients had “outstanding” responses to treatment, Dr. Kirkham noted: The mean Eczema Area and Severity Index score before dupilumab treatment was 21, falling to 4.2 with treatment, indicating a mean 80% improvement.

Co-author Joseph Nathan, MBChB, of London North West Healthcare NHS Trust, who collaborated on the research while working within Dr. Kirkham’s group, said separately: “The concern that patients have is that when they start a medication and develop a side effect is that the medication is going to be stopped.”

Clinicians treating the patients took a conservative approach, prescribing NSAIDs such as cyclooxygenase-2 inhibitors or altering the frequency with which dupilumab was given.

With this approach, MSK symptoms resolved in 15 patients who remained on treatment and in seven who had to stop dupilumab. There were four patients, however, who had unresolved symptoms even once dupilumab treatment had been stopped.
 

Altering the local cytokine balance

Dupilumab is a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. This results in blocking the function of not only IL-4 but also IL-13.

Dr. Kirkham and colleagues think this might not only alter the balance of cytokines in the skin but also in the joints and entheses with IL-17, IL-23, or even tumor necrosis factor playing a possible role. Another thought is that many circulating T-cells in the skin move to the joints and entheses to trigger symptoms.

IL-13 inhibition does seem to be important, as another British research team, from the Centre for Epidemiology Versus Arthritis at the University of Manchester (England), has found.

At the recent annual meeting of the British Society for Rheumatology, Sizheng Steven Zhao, MBChB, PhD, and colleagues reported that among people who carried a genetic variant predisposing them to having low IL-13 function, there was a higher risk for inflammatory diseases such as psoriatic arthritis and other spondyloarthropathy-related diseases.

Sara Freeman/Frontline Medical News

Dermatology perspective

Approved by the U.S. Food and Drug Administration in 2017, dupilumab has since been hailed as a “breakthrough” in atopic dermatitis treatment. Given as a subcutaneous injection every 2 weeks, it provides a much-needed option for people who have moderate-to-severe disease and have tried other available treatments, including corticosteroids.

Dupilumab has since also been approved for asthma, chronic sinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis and is used off-label for other skin conditions such as contact dermatitis, chronic spontaneous urticaria, and alopecia areata.

“Dupilumab, like a lot of medications for atopic dermatitis, is a relatively new drug, and we are still learning about its safety,” Joel M. Gelfand, MD, MSCE, of the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

“Inflammatory arthritis has been reported in patients treated with dupilumab, and this new study provides some useful estimates,” added Dr. Gelfand, who is a professor of dermatology and epidemiology and directs the Psoriasis and Phototherapy Treatment Center, Philadelphia.

“There was no control group,” Dr. Gelfand said, so “a causal relationship cannot be well established based on these data alone. The mechanism is not known but may result from a shifting of the immune system.”

Dr. Zhao observed: “We don’t know what the natural history of these adverse events is. We don’t know if stopping the drug early will prevent long-term adverse events. So, we don’t know if people will ultimately develop permanent psoriatic arthritis if we don’t intervene quick enough when we observe an adverse event.”

Being aware of the possibility of rheumatic side effects occurring with dupilumab and similar agents is key, Dr. Gelfand and Dr. Kirkham both said independently.

“I have personally seen this entity in my practice,” Dr. Gelfand said. “It is important to clinicians prescribing dupilumab to alert patients about this potential side effect and ask about joint symptoms in follow-up.”

Dr. Kirkham said: “Prescribers need to be aware of it, because up until now it’s been just very vaguely discussed as sort of aches and pains, arthralgias, and it’s a much more specific of a kind of syndrome of enthesitis, arthritis, tenosynovitis – a little like psoriatic arthritis.”

Not everyone has come across these side effects, however, as Steven Daveluy, MD, associate professor and dermatology program director at Wayne State University, Detroit, said in an interview.

“This article and the other case series both noted the musculoskeletal symptoms occurred in about 5% of patients, which surprised me since I haven’t seen it in my practice and have enough patients being treated with dupilumab that I would expect to see a case at that rate,” Dr. Daveluy said.

“The majority of cases are mild and respond to treatment with anti-inflammatories like naproxen, which is available over the counter. It’s likely that patients with a mild case could simply treat their pain with naproxen that’s already in their medicine cabinet until it resolves, never bringing it to the doctor’s attention,” he suggested.

“Dupilumab is still a safe and effective medication that can change the lives of patients suffering from atopic dermatitis,” he said.

“Awareness of this potential side effect can help dermatologists recognize it early and work together with patients to determine the best course of action.”

All research mentioned in this article was independently supported. Dr. Kirkham, Mr. Nathan, Dr. Zhao, and Dr. Daveluy report no relevant financial relationships. Dr. Gelfand has served as a consultant for numerous pharmaceutical companies and receives research grants from Amgen, Boehringer Ingelheim, and Pfizer. He is a co-patent holder of resiquimod for treatment of cutaneous T-cell lymphoma.

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

Around 5% of patients treated with dupilumab (Dupixent) for moderate-to-severe atopic dermatitis experience musculoskeletal (MSK) symptoms, according to the results of a descriptive study.

The main MSK symptom seen in the observational cohort was enthesitis, but some patients also experienced arthritis and tenosynovitis a median of 17 weeks after starting dupilumab treatment. Together these symptoms represent a new MSK syndrome, say researchers from the United Kingdom.

“The pattern of MSK symptoms and signs is characteristic of psoriatic arthritis/peripheral spondyloarthritis,” Bruce Kirkham, MD, and collaborators report in Arthritis & Rheumatology.

“We started a few years ago and have been following the patients for quite a long time,” Dr. Kirkham, a consultant rheumatologist at Guy’s and St. Thomas’ NHS Foundation Trust, London, told this news organization.

Characterizing the MSK symptoms

Of 470 patients with atopic dermatitis who started treatment with dupilumab at Guy’s and St. Thomas’ NHS Foundation Trust between October 2018 and February 2021, 36 (7.65%) developed rheumatic symptoms and were referred to the rheumatology department. These individuals had their family history assessed and thorough MSK evaluations, which included antibody and inflammatory markers, ultrasound of the peripheral small joints, and MRI of the large joints and spine.

A total of 26 (5.5%) patients – 14 of whom were male – had inflammatory enthesitis, arthritis, and/or tenosynovitis. Of the others, seven had osteoarthritis and three had degenerative spine disease.

Enthesitis was the most common finding in those with rheumatic symptoms, occurring on its own in 11 patients, with arthritis in three patients, and tenosynovitis in two patients.  

These symptoms appeared 2-48 weeks after starting dupilumab treatment and were categorized as mild in 16 (61%) cases, moderate in six cases, and severe in four cases.

No specific predictors of the MSK symptoms seen were noted. Patient age, sex, duration of their atopic dermatitis, or how their skin condition had been previously treated did not help identify those who might develop rheumatic problems.
 

Conservative management approach

All patients had “outstanding” responses to treatment, Dr. Kirkham noted: The mean Eczema Area and Severity Index score before dupilumab treatment was 21, falling to 4.2 with treatment, indicating a mean 80% improvement.

Co-author Joseph Nathan, MBChB, of London North West Healthcare NHS Trust, who collaborated on the research while working within Dr. Kirkham’s group, said separately: “The concern that patients have is that when they start a medication and develop a side effect is that the medication is going to be stopped.”

Clinicians treating the patients took a conservative approach, prescribing NSAIDs such as cyclooxygenase-2 inhibitors or altering the frequency with which dupilumab was given.

With this approach, MSK symptoms resolved in 15 patients who remained on treatment and in seven who had to stop dupilumab. There were four patients, however, who had unresolved symptoms even once dupilumab treatment had been stopped.
 

Altering the local cytokine balance

Dupilumab is a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. This results in blocking the function of not only IL-4 but also IL-13.

Dr. Kirkham and colleagues think this might not only alter the balance of cytokines in the skin but also in the joints and entheses with IL-17, IL-23, or even tumor necrosis factor playing a possible role. Another thought is that many circulating T-cells in the skin move to the joints and entheses to trigger symptoms.

IL-13 inhibition does seem to be important, as another British research team, from the Centre for Epidemiology Versus Arthritis at the University of Manchester (England), has found.

At the recent annual meeting of the British Society for Rheumatology, Sizheng Steven Zhao, MBChB, PhD, and colleagues reported that among people who carried a genetic variant predisposing them to having low IL-13 function, there was a higher risk for inflammatory diseases such as psoriatic arthritis and other spondyloarthropathy-related diseases.

Sara Freeman/Frontline Medical News

Dermatology perspective

Approved by the U.S. Food and Drug Administration in 2017, dupilumab has since been hailed as a “breakthrough” in atopic dermatitis treatment. Given as a subcutaneous injection every 2 weeks, it provides a much-needed option for people who have moderate-to-severe disease and have tried other available treatments, including corticosteroids.

Dupilumab has since also been approved for asthma, chronic sinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis and is used off-label for other skin conditions such as contact dermatitis, chronic spontaneous urticaria, and alopecia areata.

“Dupilumab, like a lot of medications for atopic dermatitis, is a relatively new drug, and we are still learning about its safety,” Joel M. Gelfand, MD, MSCE, of the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

“Inflammatory arthritis has been reported in patients treated with dupilumab, and this new study provides some useful estimates,” added Dr. Gelfand, who is a professor of dermatology and epidemiology and directs the Psoriasis and Phototherapy Treatment Center, Philadelphia.

“There was no control group,” Dr. Gelfand said, so “a causal relationship cannot be well established based on these data alone. The mechanism is not known but may result from a shifting of the immune system.”

Dr. Zhao observed: “We don’t know what the natural history of these adverse events is. We don’t know if stopping the drug early will prevent long-term adverse events. So, we don’t know if people will ultimately develop permanent psoriatic arthritis if we don’t intervene quick enough when we observe an adverse event.”

Being aware of the possibility of rheumatic side effects occurring with dupilumab and similar agents is key, Dr. Gelfand and Dr. Kirkham both said independently.

“I have personally seen this entity in my practice,” Dr. Gelfand said. “It is important to clinicians prescribing dupilumab to alert patients about this potential side effect and ask about joint symptoms in follow-up.”

Dr. Kirkham said: “Prescribers need to be aware of it, because up until now it’s been just very vaguely discussed as sort of aches and pains, arthralgias, and it’s a much more specific of a kind of syndrome of enthesitis, arthritis, tenosynovitis – a little like psoriatic arthritis.”

Not everyone has come across these side effects, however, as Steven Daveluy, MD, associate professor and dermatology program director at Wayne State University, Detroit, said in an interview.

“This article and the other case series both noted the musculoskeletal symptoms occurred in about 5% of patients, which surprised me since I haven’t seen it in my practice and have enough patients being treated with dupilumab that I would expect to see a case at that rate,” Dr. Daveluy said.

“The majority of cases are mild and respond to treatment with anti-inflammatories like naproxen, which is available over the counter. It’s likely that patients with a mild case could simply treat their pain with naproxen that’s already in their medicine cabinet until it resolves, never bringing it to the doctor’s attention,” he suggested.

“Dupilumab is still a safe and effective medication that can change the lives of patients suffering from atopic dermatitis,” he said.

“Awareness of this potential side effect can help dermatologists recognize it early and work together with patients to determine the best course of action.”

All research mentioned in this article was independently supported. Dr. Kirkham, Mr. Nathan, Dr. Zhao, and Dr. Daveluy report no relevant financial relationships. Dr. Gelfand has served as a consultant for numerous pharmaceutical companies and receives research grants from Amgen, Boehringer Ingelheim, and Pfizer. He is a co-patent holder of resiquimod for treatment of cutaneous T-cell lymphoma.

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

Around 5% of patients treated with dupilumab (Dupixent) for moderate-to-severe atopic dermatitis experience musculoskeletal (MSK) symptoms, according to the results of a descriptive study.

The main MSK symptom seen in the observational cohort was enthesitis, but some patients also experienced arthritis and tenosynovitis a median of 17 weeks after starting dupilumab treatment. Together these symptoms represent a new MSK syndrome, say researchers from the United Kingdom.

“The pattern of MSK symptoms and signs is characteristic of psoriatic arthritis/peripheral spondyloarthritis,” Bruce Kirkham, MD, and collaborators report in Arthritis & Rheumatology.

“We started a few years ago and have been following the patients for quite a long time,” Dr. Kirkham, a consultant rheumatologist at Guy’s and St. Thomas’ NHS Foundation Trust, London, told this news organization.

Characterizing the MSK symptoms

Of 470 patients with atopic dermatitis who started treatment with dupilumab at Guy’s and St. Thomas’ NHS Foundation Trust between October 2018 and February 2021, 36 (7.65%) developed rheumatic symptoms and were referred to the rheumatology department. These individuals had their family history assessed and thorough MSK evaluations, which included antibody and inflammatory markers, ultrasound of the peripheral small joints, and MRI of the large joints and spine.

A total of 26 (5.5%) patients – 14 of whom were male – had inflammatory enthesitis, arthritis, and/or tenosynovitis. Of the others, seven had osteoarthritis and three had degenerative spine disease.

Enthesitis was the most common finding in those with rheumatic symptoms, occurring on its own in 11 patients, with arthritis in three patients, and tenosynovitis in two patients.  

These symptoms appeared 2-48 weeks after starting dupilumab treatment and were categorized as mild in 16 (61%) cases, moderate in six cases, and severe in four cases.

No specific predictors of the MSK symptoms seen were noted. Patient age, sex, duration of their atopic dermatitis, or how their skin condition had been previously treated did not help identify those who might develop rheumatic problems.
 

Conservative management approach

All patients had “outstanding” responses to treatment, Dr. Kirkham noted: The mean Eczema Area and Severity Index score before dupilumab treatment was 21, falling to 4.2 with treatment, indicating a mean 80% improvement.

Co-author Joseph Nathan, MBChB, of London North West Healthcare NHS Trust, who collaborated on the research while working within Dr. Kirkham’s group, said separately: “The concern that patients have is that when they start a medication and develop a side effect is that the medication is going to be stopped.”

Clinicians treating the patients took a conservative approach, prescribing NSAIDs such as cyclooxygenase-2 inhibitors or altering the frequency with which dupilumab was given.

With this approach, MSK symptoms resolved in 15 patients who remained on treatment and in seven who had to stop dupilumab. There were four patients, however, who had unresolved symptoms even once dupilumab treatment had been stopped.
 

Altering the local cytokine balance

Dupilumab is a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. This results in blocking the function of not only IL-4 but also IL-13.

Dr. Kirkham and colleagues think this might not only alter the balance of cytokines in the skin but also in the joints and entheses with IL-17, IL-23, or even tumor necrosis factor playing a possible role. Another thought is that many circulating T-cells in the skin move to the joints and entheses to trigger symptoms.

IL-13 inhibition does seem to be important, as another British research team, from the Centre for Epidemiology Versus Arthritis at the University of Manchester (England), has found.

At the recent annual meeting of the British Society for Rheumatology, Sizheng Steven Zhao, MBChB, PhD, and colleagues reported that among people who carried a genetic variant predisposing them to having low IL-13 function, there was a higher risk for inflammatory diseases such as psoriatic arthritis and other spondyloarthropathy-related diseases.

Sara Freeman/Frontline Medical News

Dermatology perspective

Approved by the U.S. Food and Drug Administration in 2017, dupilumab has since been hailed as a “breakthrough” in atopic dermatitis treatment. Given as a subcutaneous injection every 2 weeks, it provides a much-needed option for people who have moderate-to-severe disease and have tried other available treatments, including corticosteroids.

Dupilumab has since also been approved for asthma, chronic sinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis and is used off-label for other skin conditions such as contact dermatitis, chronic spontaneous urticaria, and alopecia areata.

“Dupilumab, like a lot of medications for atopic dermatitis, is a relatively new drug, and we are still learning about its safety,” Joel M. Gelfand, MD, MSCE, of the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

“Inflammatory arthritis has been reported in patients treated with dupilumab, and this new study provides some useful estimates,” added Dr. Gelfand, who is a professor of dermatology and epidemiology and directs the Psoriasis and Phototherapy Treatment Center, Philadelphia.

“There was no control group,” Dr. Gelfand said, so “a causal relationship cannot be well established based on these data alone. The mechanism is not known but may result from a shifting of the immune system.”

Dr. Zhao observed: “We don’t know what the natural history of these adverse events is. We don’t know if stopping the drug early will prevent long-term adverse events. So, we don’t know if people will ultimately develop permanent psoriatic arthritis if we don’t intervene quick enough when we observe an adverse event.”

Being aware of the possibility of rheumatic side effects occurring with dupilumab and similar agents is key, Dr. Gelfand and Dr. Kirkham both said independently.

“I have personally seen this entity in my practice,” Dr. Gelfand said. “It is important to clinicians prescribing dupilumab to alert patients about this potential side effect and ask about joint symptoms in follow-up.”

Dr. Kirkham said: “Prescribers need to be aware of it, because up until now it’s been just very vaguely discussed as sort of aches and pains, arthralgias, and it’s a much more specific of a kind of syndrome of enthesitis, arthritis, tenosynovitis – a little like psoriatic arthritis.”

Not everyone has come across these side effects, however, as Steven Daveluy, MD, associate professor and dermatology program director at Wayne State University, Detroit, said in an interview.

“This article and the other case series both noted the musculoskeletal symptoms occurred in about 5% of patients, which surprised me since I haven’t seen it in my practice and have enough patients being treated with dupilumab that I would expect to see a case at that rate,” Dr. Daveluy said.

“The majority of cases are mild and respond to treatment with anti-inflammatories like naproxen, which is available over the counter. It’s likely that patients with a mild case could simply treat their pain with naproxen that’s already in their medicine cabinet until it resolves, never bringing it to the doctor’s attention,” he suggested.

“Dupilumab is still a safe and effective medication that can change the lives of patients suffering from atopic dermatitis,” he said.

“Awareness of this potential side effect can help dermatologists recognize it early and work together with patients to determine the best course of action.”

All research mentioned in this article was independently supported. Dr. Kirkham, Mr. Nathan, Dr. Zhao, and Dr. Daveluy report no relevant financial relationships. Dr. Gelfand has served as a consultant for numerous pharmaceutical companies and receives research grants from Amgen, Boehringer Ingelheim, and Pfizer. He is a co-patent holder of resiquimod for treatment of cutaneous T-cell lymphoma.

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