Dupilumab Delivers in Erythrodermic Atopic Dermatitis

Patients with severe erythrodermic atopic dermatitis (AD) had significant improvements with dupilumab (Dupixent) monotherapy or with concomitant topical corticosteroids, according to a post-hoc analysis of six randomized trials.

After 16 weeks, the involved body surface area (BSA) decreased by 40-63%, while the Eczema Area and Severity Index (EASI) decreased by 59-79%, and pruritus score decreased by 34-56%. Statistically significant improvement was evident within the first week of treatment, reported Amy Paller, MD, of the Ann and Robert H. Lurie Children's Hospital of Chicago, and co-authors.

The symptomatic improvement was accompanied by significant decreases in serum levels of inflammatory biomarkers, they noted in JAMA Dermatology.

"Erythrodermic AD is a serious manifestation of AD that can lead to health-threatening complications," the authors wrote in their discussion of the findings. "In the analyzed trials, patients with erythrodermic AD had higher baseline disease severity ... and reported worse quality of life at baseline compared with the overall populations."

"Overall, dupilumab was well tolerated, with most adverse events [AEs] being mild or moderate in severity, and with no imbalance in TEAEs [treatment-emergent AEs] and treatment-emergent serious adverse events between dupilumab and placebo groups," they added.

The subgroup analysis provided much-needed data on clinical management of erythrodermic AD while adding to an existing body of literature showing the safety and efficacy of dupilumab in different AD populations, noted Dawn Z. Eichenfield, MD, PhD, of the University of California San Diego, in an accompanying editorial.

"There remains a paucity of literature describing efficacious therapies in the treatment of erythrodermic AD," she wrote. "The major strength of this analysis is that the data are derived from six double-blind RCTs [randomized controlled trials] with international representation and a total sample size of 209 patients."

The retrospective nature of the analysis and the small number of patients with erythrodermic AD in comparison to the overall population in the six trials [N=3,075] are the principal limitations, she added.

"Erythrodermic AD is a severe clinical presentation of AD with high morbidity and mortality, which can be challenging to manage," Eichenfield concluded. "The implementation of dupilumab and other advanced systemic therapies in AD will provide new tools for management of erythrodermic AD."

Erythrodermic AD is an uncommon inflammatory skin disorder characterized by diffuse erythema involving more than 90% of BSA and accompanied by scaling and pruritus. The condition has associations with various skin diseases, as well as drug reactions and cancers. Limited data suggest erythrodermic AD increases mortality risk, either through complications of the condition or underlying disease mechanisms, Paller and co-authors noted.

Topical treatments, including corticosteroids, are an important adjunctive therapy for erythrodermic AD but have a limited role overall, as application of the therapy to virtually the entire body surface is impractical. Oral steroids are unsuitable for erythrodermic AD, and systemic nonsteroidal immunosuppressants, though often used off label, have limited data to support long-term safety and efficacy, the authors continued.

Dupilumab blocks the shared receptor component for interleukin-4 and -13, which are key drivers of type 2 inflammation. In moderate to severe AD, dupilumab monotherapy and with concomitant topical corticosteroids improved signs, symptoms, and quality of life.

Paller and colleagues reported findings from an analysis of the subgroup of patients with erythrodermic AD enrolled in six international, multicenter, randomized trials of dupilumab in moderate to severe AD.

The 209 patients included in the post-hoc analysis met erythrodermic AD diagnostic criteria of at least 90% BSA involvement and a Global Individual Sign Score for erythema of at least 1. Patients received dupilumab once weekly or every 2 weeks or matching placebo, with or without concomitant topical steroids. The primary outcomes were change in BSA, EASI score, and Peak Pruritus Numerical Rating Scale (PP-NRS) at 16 weeks.

The analysis comprised 136 patients who received dupilumab monotherapy or placebo and 73 who received dupilumab or placebo with topical steroids. Median ages of patients treated with monotherapy or with steroids were 31 and 39, respectively, and men accounted for 71.3% and 74% of the patients in the two groups.

Dupilumab monotherapy administered weekly or every 2 weeks improved all three key outcomes versus placebo:

• Decrease in BSA: 42.0% and 39.9% vs 17.2% (P=0.03)
• Decrease in EASI: 58.5% and 58.3% vs 22.3% (P=0.004 and P=0.003)
• Decrease in PP-NRS: 45.9% and 33.9% vs 0.6% (P<0.001)

Concomitant topical steroids increased the advantage of dupilumab over placebo, despite smaller numbers:

• Decrease in BSA: 63.2% and 56.1% vs 14.5% (P<0.001)
• Decrease in EASI: 78.9% and 70.6% vs 19.3% (P<0.001)
• Decrease in PP-NRS: 53.0% and 55.7% vs 26.0% (P=0.006 and P=0.01)

Dupilumab, with or without concomitant topical steroids, was associated with statistically significant reductions in serum thymus and activation-regulated chemokine, total immunoglobulin E, and serum lactate dehydrogenase (P<0.001 versus placebo).

The most common AEs in dupilumab-treated patients were injection-site reactions, conjunctivitis, and nasopharyngitis.

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