麻豆传媒

ORLANDO -- About 40% of patients with moderate or severe atopic dermatitis (AD) had complete or near-complete clearance of involved skin areas after 16 weeks of treatment with the dual cytokine inhibitor dupilumab, a randomized trial showed.

The improvement was maintained out to 52 weeks in most patients. By the Eczema Area and Severity Index (EASI), two-thirds of patients had at least 75% improvement (EASI 75) in skin status at 16 and 52 weeks, according to , of Oregon Medical Research Center in Portland, and colleagues.

Patients treated with dupilumab plus topical corticosteroids had about 60% improvement in pruritus at 16 and 52 weeks, as compared with about 30% of patients who received topical steroids and a placebo, they reported at the American Academy of Dermatology annual meeting.

"The is the first randomized, placebo-controlled study of a biologic for atopic dermatitis for a 1-year period," Blauvelt said. "Both dose regimens of dupilumab plus topical corticosteroids provided significant improvement versus placebo in multiple efficacy measures and patient-reported outcomes."

"Blocking signaling of the type 2 (Th2) cytokines IL-4 and IL-13 leads to sustained control of moderate-to-severe atopic dermatitis during the 52-week treatment period. There are ongoing confirmatory phase III programs in asthma and other allergic diseases," he added.

Similar results emerged from a phase II trial involving children, ages 6 to 17 years, presented at the meeting. In this study, baseline EASI scores declined by as much as 76% at 12 weeks.

The results with dupilumab were "clearly impressive" but the key unknown about the drug, and others like it, is staying power, said , of the University of Pennsylvania in Philadelphia.

"This is a first-in-class drug that shows great efficacy, but if the lessons from biologics apply here, people lose efficacy over time," said Gelfand, who was not involved in the study. "It will be a big advance, but we will still have a lot of work to do. Patients with atopic dermatitis have miserable skin disease. If they only respond for a couple of years, then we'll definitely have to come up with more strategies to help them."

The Th2 cytokines IL-4 and IL-13 mediate multiple features of AD, as well as asthma and other atopic and allergic diseases. The monoclonal antibody dupilumab was developed to target both cytokines. In , treatment with dupilumab monotherapy led to significant improvement in signs and symptoms of atopic at 16 weeks.

Blauvelt reported findings from another phase III evaluation of dupilumab in AD, this time paired with topical steroids. Patients were randomized 2:1:2 to three treatment groups: weekly subcutaneous dupilumab; subcutaneous dupilumab administered every 2 weeks (q2w); or weekly placebo. Patients in all three groups also received topical corticosteroids.

The primary endpoint was an investigator global assessment (IGA) score of 0 or 1 (complete or near-complete clearance) plus at least a 2-point improvement in the IGA by week 16. The key secondary endpoint was the proportion of patients achieving EASI 75 at 16 weeks.

Data analysis included 740 patients, who had a median age of about 35, baseline body surface area involvement of 50% to 60%, and median EASI score of about 30. The 16-week results showed that 39% of patients in each dupilumab group met the primary endpoint, as compared with 12% of the placebo group (P<0.0001). At week 52, 36% of patients in the dupilumab q2w group met the primary endpoint, 39% with weekly dupilumab, and 13% with placebo (P<0.0001).

Analysis of the secondary endpoint showed that 69% of patients in the dupilumab q2w group achieved EASI 75, 64% in the weekly dupilumab group, and 23% of the placebo group (P<0.0001). At 52 weeks, the EASI 75 rates were 65% with dupilumab q2w, 64% with weekly dupilumab, and 22% with placebo (P<0.0001).

Analysis of EASI 50 and EASI 90 rates also showed large differences in favor of the dupilumab arms at 16 and 52 weeks.

Two quality-of-life assessment tools demonstrated a twofold difference in scores in favor of both dupilumab groups at 16 and 52 weeks (P<0.0001 for all comparisons). Adverse event profiles were similar among the three treatment groups.

The pediatric study involved 40 adolescents (ages 12 to 17) with moderate or severe AD and 38 children (ages 6 to 11) with severe AD. The patients received a single subcutaneous dose of 2 or 4 mg/kg, followed 8 weeks later by four weekly dose, said , of the University of Sheffield in England. Many of the patients had been hospitalized, some for weeks.

The 12-week results in the adolescents showed 66.4% reduction in baseline EASI score with the 2 mg/kg dose of dupilumab and 69.7% with the higher dose. In the younger children, improvement averaged 63.4% with dupilumab 2 mg/kg and 76.2% with 4 mg/kg. Pruritus scores decreased by 30% to 40% in both age groups. Dramatic improvement occurred within the first 4 weeks, after a single dose of dupilumab.

Adverse events were mostly mild and transient.

"After one dose, the dupilumab is blocking all of the IL-4/IL-13 targets, and this translates into this amazing clinical picture, where we see a reduction in EASI of 60% with one injection, and four injections, almost 70% reduction," said Cork.