• Skin Diseases
• Dermatology Clinical Trials

• Skin Diseases
• Dermatology
• Dermatology Clinical Trials

Marius Ardeleanu, MD, Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA, reviewed safety and efficacy results from the phase 2b Study of Dupilumab Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis [NCT01859988].

Atopic dermatitis (AD) is a common, chronic skin condition induced by a type 2 helper (Th2) T cell-mediated response to various environmental antigens. These cells release cytokines that promote occurrence and recurrence of AD. Two Th2 cytokines thought likely to be involved in the pathogenesis of AD are interleukin (IL)-4 and IL-13 [Lebwohl MG et al. J Clin Aesthet Dermatol. 2013]. Dupilumab is a monoclonal antibody that targets the IL-4 receptor α subunit, blocking intracellular signaling of both IL-4 and IL-13. Data from early clinical trials have suggested that dupilumab is safe and efficacious for adults with moderate-to-severe AD [Beck LA et al. N Engl J Med. 2014].

The multicenter, international, double-blind, placebo-controlled, randomized, dose-ranging study was designed to test the safety and efficacy of subcutaneous injections of dupilumab in 380 adults with chronic moderate-to-severe AD poorly controlled on current topical medications. Patients were divided into 5 treatment groups. On day 1 of the 16-week study, patients received a loading dose of either 400 or 600 mg. The 5 groups of patients then received dupilumab in doses ranging from 100 mg every 4 weeks to 300 mg every week. All groups were followed for an additional 16 weeks.

The primary end point was percent change in the Eczema Area and Severity Index (EASI) from baseline to week 16. Key secondary end points included the proportion of patients who achieved a reduction of 50%, 75%, or 90% in the EASI (EASI-50/75/90); changes in various measurements of pruritus and skin condition; and safety.

All patients had chronic AD for ≥ 3 years (EASI ≥ 16), with a documented inadequate response to topical treatments for at least 6 months prior to the screening visit. Patients who had received prior treatment with dupilumab, had an active infection, or had used topical medications for AD within 1 week of baseline were excluded from the trial. Mean patient age was 37 years, and mean duration of time with AD was 31 years.

Patients who received any regimen of dupilumab achieved a significantly greater mean percent change in the EASI compared with placebo (all P < .0001); the 300-mg dose given every week produced the greatest percent change. According to Dr Ardeleanu, most of the response was evident within 4 to 6 weeks.

Relative to the secondary end points, almost every dose regimen was statistically more likely to achieve EASI-50/75/90 throughout 16 weeks compared with placebo (P range, < .05 to < .0001); the only exception was the 100-mg dose once weekly, which did not reach statistical significance for EASI-50. Although patients who took any dose of dupilumab achieved an improved Investigator's Global Assessment response as well as self-reported reductions in pruritus, the 300-mg weekly and every 2-week doses showed the most consistent benefits among all the outcomes.

The most common adverse events were nasopharyngitis, headache, and injection site reactions, all of which were higher in the dupilumab groups. There were no dose-limiting toxicities. Based on these results, Dr Ardeleanu noted that the 2 highest dose regimens will be further tested in a phase 3 trial and that a maintenance study will be done to test whether lower doses of dupilumab can maintain the improvements sustained with higher doses.

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