Efficacy and Safety of Dupilumab in Patients With Erythrodermic Atopic Dermatitis

Abstract

ImportanceErythrodermic atopic dermatitis (AD) is a severe AD subtype defined by extensive skin involvement, leading to complications and sometimes hospitalization.ObjectiveTo assess dupilumab’s efficacy and safety in patients with erythrodermic AD in clinical trials.Design, Setting, and ParticipantsThis post hoc analysis included patients enrolled in 6 multicenter, multinational, randomized, double-blind, placebo-controlled trials. Patients included in this analysis met erythrodermic AD criteria of 90% or greater body surface area (BSA) affected by AD and Global Individual Sign Score for erythema of 1 or higher. Data analyses for this post hoc analysis were conducted between March 5, 2019, and October 24, 2020.InterventionsDupilumab once weekly or every 2 weeks, or placebo, either as monotherapy or with concomitant topical corticosteroids (TCS).Main Outcomes and MeasuresEfficacy (BSA, Eczema Area and Severity Index [EASI] score, Peak Pruritus Numerical Rating Scale [PP-NRS] score), changes in serum biomarkers (thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase), and safety (incidence of adverse events) at week 16. Data were pooled within each regimen; monotherapy and concomitant TCS results are shown separately.ResultsOf 3075 randomized patients, 209 met criteria for erythrodermic AD at baseline, with the median age being 31 and 39 years in the monotherapy and concomitant TCS trials, respectively, similar to the overall populations (34 and 36 years, respectively); 71.3% (n = 97) and 74.0% (n = 54) of patients, respectively, were male (compared with 58.7% and 60.6% in the overall populations). In patients with erythrodermic AD, dupilumab once weekly and every 2 weeks vs placebo significantly improved percentage of BSA affected by AD (least squares mean percent change [SE]) with monotherapy (−42.0% [7.7%] and −39.9% [6.5%] vs −17.2% [11.0%]; P = .03) and concomitant TCS (−63.2% [6.7%] and −56.1% [9.1%] vs −14.5% [7.3%]; P < .001); EASI score with monotherapy (−58.5% [9.0%] and −58.3% [7.9%] vs −22.3% [12.4%]; P = .004 and P = .003, respectively) and concomitant TCS (−78.9% [7.8%] and −70.6% [10.1%] vs 19.3% [8.2%]; P < .001); and PP-NRS score in monotherapy (−45.9% [7.8%] and −33.9% [6.6%] vs −0.6% [9.4%]; P < .001) and concomitant therapy (−53.0% [8.1%] and −55.7% [10.8%] vs −26.0% [8.8%]; P = .006 and P = .01, respectively). Nominally statistically significant improvement was seen as early as week 1 (EASI and PP-NRS scores with monotherapy). Biomarker levels were significantly reduced vs placebo. The most frequent adverse events in dupilumab-treated patients were injection-site reaction, conjunctivitis, and nasopharyngitis.Conclusions and RelevanceIn this post hoc analysis of 6 randomized clinical trials, treatment with dupilumab resulted in rapid, sustained improvements in AD signs and symptoms with acceptable safety in patients with erythrodermic AD, similar to those in the trials’ overall patient population.Trial RegistrationClinicalTrials.gov Identifiers: NCT01859988, NCT02277743, NCT02277769, NCT03054428, NCT02260986, NCT02755649

Therapeutic Relief for Erythrodermic Atopic Dermatitis

“…The major strength of this analysis is that the data are derived from 6 double-blind RCTs with international representation and a total sample size of 209 patients, the largest known evaluated data set of patients with erythrodermic AD . One of the main limitations of this analysis is its retrospective post hoc nature.…”

“…Of the 3075 randomized patients in the study, 209 adolescents and adults met criteria for erythrodermic AD at baseline and 183 completed 16 weeks of treatment with dupilumab . Not surprisingly, patients with erythrodermic AD had worse quality of life at baseline.…”

“…In this issue of JAMA Dermatology , Paller and colleagues report the post hoc analysis of dupilumab treatment in patients with erythrodermic AD from 6 placebo-controlled RCTs . Dupilumab is a fully human monoclonal antibody directed against the α subunit of the IL-4 receptor that blocks the signaling of type 2 cytokines IL-4 and IL-13, which are important drivers of atopic and allergic diseases such as AD, asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis .…”

“…Paller and colleagues analyzed effects of dupilumab with and without concomitant topical corticosteroid use in adults and adolescents with erythrodermic AD using all available data from multicenter international trials . In addition to characterizing the baseline demographics and disease characteristics, the authors evaluated dupilumab’s clinical efficacy and overall safety and assessed the effect of treatment on key serum biomarker levels …”

Erythroderma: A Retrospective Study of 212 Patients Hospitalized in a Tertiary Center in Lower Silesia, Poland

“…The authors assumed that both drugs were effective in treating these dermatoses [52]. There are fewer reports on the treatment of erythrodermic atopic dermatitis, but some studies have shown the efficacy of dupilumab in treating erythrodermic atopic dermatitis [53,54].…”