Amy S. Paller, MD

Patients with erythrodermic atopic dermatitis (AD) showed rapid and sustained improvements in symptoms after treatment with dupilumab and concomitant topical corticosteroids (TCS) according to a recent analysis of 6 trials.¹

The study’s investigators set out to examine the efficacy and safety profile of dupilumab (with and without concomitant TCS therapy) on patients with erythrodermic AD, a condition known to be a potentially-severe subtype of AD.

Erythrodermic AD is an inflammatory skin condition which the team wrote is associated with diffuse erythema involving over 90% of body surface area (BSA). The condition is also associated with pruritus and scaling.

The study was authored by Amy S. Paller, MD, from Northwestern University’s Feinberg School of Medicine in Chicago.

“We analyzed effects of dupilumab with or without concomitant TCS in adults and adolescents with erythrodermic AD using all available data from multicenter, international clinical trials performed by Sanofi and Regeneron Pharmaceuticals Inc using dupilumab in patients with moderate to severe AD,” Paller and colleagues wrote.

Research and Methods

The investigators conducted a post-hoc analysis of 209 erythrodermic AD patients in a total of 6 randomized, placebo-controlled, clinical trials on dupilumab therapy.

The trial data included in their analysis was drawn from their research on dupilumab treatment used either as concomitant therapy with topical corticosteroid use or as monotherapy, comparing either to placebo.

The investigators gathered their data for the post-hoc analysis between March of 2019 and October of 2020.

Their primary endpoints involved the following points of information during their analysis:

• Efficacy of treatment, as measured by BSA, Peak Pruritus Numerical Rating Scale (PP-NRS), and Eczema Area and Severity Index (EASI) rating
• Serum biomarker changes (total immunoglobulin E, thymus and activation-regulated chemokine, lactate dehydrogenase)
• Treatment safety, as measured by adverse events, after 16 weeks.

The investigators’ data was pooled for each regimen of treatment, with results for both monotherapy and concomitant TCS being labeled differently by the team.

Study Findings

The research team’s analyses led to the conclusion that out of their 3,075 patients who had been randomized, 209 were found to have met the baseline erythrodermic AD criteria.

The median age of the AD patients included was in the range of 31 and 39 for the monotherapy arm and concomitant TCS arm, respectively.

The investigators added that 71.3% (n = 97) of the monotherapy arm and 74.0% (n = 54) of the concomitant TCS arm were found to be men, compared with 58.7% and 60.6% in the overall populations from which the team drew.

Overall, the post-hoc analysis conducted by the investigators indicated that dupilumab once-per-week and then later every 2 weeks improved BSA percentage affected by AD substantially.

They reported that for patients with the skin condition and given dupilumab once-per-week and for those every 2 weeks (versus placebo) there was a higher percentage of BSA affected, with concomitant TCS being −63.2% and −56.1% compared to −14.5% (P < .001) and monotherapy being −42.0% and −39.9% compared to −17.2% (P = .03).

The patients’ EASI rating with monotherapy were found to be −58.5% (9.0%) and −58.3% (7.9%) compared to −22.3% (12.4%); P = .004 and P = .003, respectively. Concomitant TCS showed an EASI of −78.9% (7.8%) and −70.6% (10.1%) compared to 19.3% (8.2%) (P < .001).

The team added that PP-NRS scores for patients in the monotherapy arm were −45.9% (7.8%) and −33.9% (6.6%) compared to −0.6% (9.4%) (P < .001). For concomitant therapy the scores were −53.0% (8.1%) and −55.7% (10.8%) compared to −26.0% (8.8%) (P = .006 and P = .01, respectively).

Even as soon as 1 week into monotherapy, the investigators wrote that nominal improvement was reported in EASI and PP-NRS scores.

The investigators also added that adverse events which appeared most often in patients given dupilumab treatment were found to be injection-site reaction, nasopharyngitis, and conjunctivitis.

“In this post hoc analysis, dupilumab as monotherapy and with concomitant TCS resulted in rapid and sustained improvements in AD signs, symptoms, and health-related quality of life in patients with erythrodermic AD,” they wrote. “Dupilumab had an acceptable safety profile that did not substantially differ in patients with erythrodermic AD and the overall population of patients with moderate to severe AD enrolled in these trials.”

References:

1. Paller AS, Silverberg JI, Cork MJ, et al. Efficacy and Safety of Dupilumab in Patients With Erythrodermic Atopic Dermatitis: A Post Hoc Analysis of 6 Randomized Clinical Trials. JAMA Dermatol. Published online February 01, 2023. doi:10.1001/jamadermatol.2022.6192.