PURPOSE OF THE STUDY:
To evaluate the effect of nemolizumab, a subcutaneously administered humanized monoclonal antibody against interleukin 31 receptor A and concomitant topical medications and oral antihistamines versus placebo on atopic dermatitis (AD)-induced pruritus.
A double-blind, placebo-controlled, parallel group, multicenter phase 3 study population of Japanese adolescents and adults aged ≥13 years (n = 215; median ages: 39 years [nemolizumab] and 40.5 years [placebo]) with a confirmed diagnosis of AD, weight of 30 to 120 kg, inadequate response to medium-potency topical corticosteroids or topical calcineurin inhibitors and oral antihistamines, and elevated visual analog scale (VAS) for pruritus and Eczema Area and Severity Index (EASI) scores.
Patients were randomly assigned in a 2:1 ratio to receive nemolizumab 60 mg subcutaneously (n = 143) versus placebo (n = 72) every 4 weeks, for 16 weeks total. Patients in both groups were allowed to continue the use of topical corticosteroids, calcineurin inhibitors, oral antihistamines, and topical moisturizers. Patients were excluded if they were on other biological therapy, phototherapy, hyposensitization therapies, or other systemic treatments. The primary end point was the percentage change in weekly mean VAS score for pruritus from the baseline, whereas secondary end points included the change in VAS score to week 4 and changes in EASI score, Dermatology Life Quality Index score and Insomnia Severity Index. Intention-to-treat models were used for analysis of all end points with patients who received at least 1 dose of nemolizumab or placebo. A mixed-effects model for repeated measures was used to analyze weekly scores. The mixed-effects model for repeated measures, analysis of covariance, and intention-to treat analysis were applied to other end points.
After 16 weeks of therapy, the mean change in VAS score from the baseline to week 16 was −42.8% ± 2.6 in the nemolizumab group versus −21.4% ± 3.6 in the placebo group, resulting in a −21.5% difference in the 2 groups (P < .001). The initial 4 week change in VAS score was −34.4% in the nemolizumab group versus −15.3% in the placebo group, resulting in a −19.3% difference between the groups. The change in EASI score >16 weeks was −45.9% (nemolizumab) versus −33.2% (placebo). In the nemolizumab group, 67% of patients had a change in Dermatology Life Quality Index score of ≥4 points, and 55% of patients had a change in an ISI score of ≤7 at week 16 versus 50% and 21%, respectively, in the placebo group. The most commonly reported adverse event was worsening AD in 24% of patients in the nemolizumab group and 21% of patients in the placebo group.
Patients with moderate to severe pruritus associated with AD, uncontrolled by topical agents and oral antihistamines, who received nemolizumab saw a reduction in pruritus based on several scoring systems, compared with those who received the placebo >16 weeks.
Currently, the only Food and Drug Administration–approved biological therapy available for moderate to severe AD is dupilumab, approved for those aged ≥6 years. Although this study included mostly adults, adolescents were included and did show some efficacy for reducing pruritus in AD. However, it is concerning that >20% of patients in the intervention group had worsening AD symptoms. Thus, further controlled trials, including the pediatric population, are needed to be able to assess overall effect on AD control.