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MIAMI BEACH -- Atopic dermatitis disease activity declined significantly in patients treated with a monoclonal antibody directed against interleukin-4 (IL-4), according to pooled data from preliminary clinical trials.

About 80% of patients treated with any of three different doses (75, 150, or 300 mg) of dupilumab had at least 25% improvement in Eczema Activity and Severity Index (EASI-25) after 4 weeks compared with 25% of placebo-treated patients, reported Eric Simpson, MD, and colleagues at the American Academy of Dermatology meeting.

The two higher doses (150 and 300 mg) of the antibody also led to significantly higher EASI response rates of 50% and 75%, respectively, said Simpson, who is from Oregon Health and Science University in Portland.

"At 4 weeks, dupilumab 150 mg and 300 mg weekly resulted in significant improvements from baseline versus placebo for the percent body surface area (BSA), EASI, and pruritus," he said. "For dupilumab 300 mg, significant improvement was seen within 2 weeks in the percent BSA and EASI."

Ongoing trials will characterize more clearly the efficacy and safety profile of the monoclonal antibody in the treatment of atopic dermatitis, he added.

Though not a life-threatening condition, atopic dermatitis can induce bothersome symptoms that significantly and adversely affect quality of life. Currently available therapies have inconsistent effects on disease control over time and can themselves cause undesirable topical and systemic adverse effects, Simpson noted.

Mechanistic studies have suggested a pathobiology involving inflammation driven by IL-4 and IL-13 signaling. Dupilumab is a fully human monoclonal antibody that targets the alpha subunit of the IL-4 receptor, disrupting IL-4 and IL-13 signaling pathways. Interference with the signaling results in potent inhibition of the T-helper 2 immune pathway.

Investigators in the U.S., Germany, Australia, and New Zealand conducted two phase Ib trials, comparing dupilumab and placebo in patients with moderate or severe atopic dermatitis.

Candidates for the trials were adults with at least a 3-year history of atopic dermatitis, EASI ≥12, investigator global assessment (IGA) ≥3 (0 to 5), ≥15% BSA involvement (≥10% for participants outside the U.S.), and a history of inadequate response to a stable regimen of topical steroids or calcineurin inhibitors.

In phase I trials, both studies had a primary endpoint of treatment-emergent adverse events through week 12. Exploratory analyses included reduction in IGA at week 4 to at least mild status (≤2), improvement in BSA and EASI, and change in the pruritus numerical rating scale.

Investigators randomized a total of 67 patients to placebo or one of the three doses of dupilumab.

A review of baseline characteristics showed a mean disease duration of about 30 years, baseline EASI score of about 30, IGA score of almost 4, BSA involvement of 40% to 50%, and pruritus score of about 6 (0 to 10).

The most commonly reported treatment-emergent adverse events were nasopharyngitis and headache, the incidence of which did not differ significantly among any of the dupilumab groups and the placebo group.

Efficacy analyses showed that placebo-treated patients initially had a worsening of EASI score, followed by about a 20% decline from baseline by week 4. In contrast, the dupilumab groups had dose-related declines of 40% to 60% at week 4 (P<0.0001). In all three groups, substantial improvement compared with placebo had emerged within 2 weeks.

Fewer than 20% of placebo-treated patients achieved EASI-50 improvement at 4 weeks, and fewer than 10% achieved EASI-75 responses.

The dupilumab groups had EASI-50 responses that ranged from almost 40% in the 75-mg dose to about 70% among patients allocated to the two higher doses (P<0.05 for all comparisons). EASI-75 responses occurred in 10% of the 75-mg group, 25% of the 150-mg group, and almost 40% of the 300-mg group. Only the EASI-75 pooled results for all three doses reached statistical significance compared with placebo (P<0.05).

Change in BSA involvement averaged about 15% at 4 weeks in the placebo group versus 25% to almost 40% in the dupilumab groups (P<0.05). Pruritus scores decreased by about 15% with placebo and 30% to 45% with dupilumab (P<0.05 to P<0.01).

The proportion of patients achieving IGA scores ≤2 was 25% with placebo, 10% with dupilumab 75 mg, 50% with dupilumab 150 mg, and 60% with the highest dose of dupilumab (P<0.05 for 300 mg).

In response to a question, Simpson said that investigators did not assess patients for microbial colonization before or after treatment.

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