BACKGROUND: Interleukin-31 may play a role in the pathobiologic mechanism of 
atopic dermatitis and pruritus. We wanted to assess the efficacy and safety of 
nemolizumab (CIM331), a humanized antibody against interleukin-31 receptor A, in 
the treatment of atopic dermatitis.
METHODS: In this phase 2, randomized, double-blind, placebo-controlled, 12-week 
trial, we assigned adults with moderate-to-severe atopic dermatitis that was 
inadequately controlled by topical treatments to receive subcutaneous 
nemolizumab (at a dose of 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight) 
or placebo every 4 weeks or an exploratory dose of 2.0 mg of nemolizumab per 
kilogram every 8 weeks. The primary end point was the percentage improvement 
from baseline in the score on the pruritus visual-analogue scale (on which a 
negative change indicates improvement) at week 12. Secondary end points included 
changes in the score on the Eczema Area and Severity Index (EASI, on which a 
negative change indicates improvement), and body-surface area of atopic 
dermatitis.
RESULTS: Of 264 patients who underwent randomization, 216 (82%) completed the 
study. At week 12, among the patients who received nemolizumab every 4 weeks, 
changes on the pruritus visual-analogue scale were -43.7% in the 0.1-mg group, 
-59.8% in the 0.5-mg group, and -63.1% in the 2.0-mg group, versus -20.9% in the 
placebo group (P<0.01 for all comparisons). Changes on the EASI were -23.0%, 
-42.3%, and -40.9%, respectively, in the nemolizumab groups, versus -26.6% in 
the placebo group. Respective changes in body-surface area affected by atopic 
dermatitis were -7.5%, -20.0%, and -19.4% with nemolizumab, versus -15.7% with 
placebo. Among the patients receiving nemolizumab every 4 weeks, treatment 
discontinuations occurred in 9 of 53 patients (17%) in the 0.1-mg group, in 9 of 
54 (17%) in the 0.5-mg group, and in 7 of 52 (13%) in the 2.0-mg group, versus 
in 9 of 53 (17%) in the placebo group.
CONCLUSIONS: In this phase 2 trial, nemolizumab at all monthly doses 
significantly improved pruritus in patients with moderate-to-severe atopic 
dermatitis, which showed the efficacy of targeting interleukin-31 receptor A. 
The limited size and length of the trial preclude conclusions regarding adverse 
events. (Funded by Chugai Pharmaceutical; XCIMA ClinicalTrials.gov number, 
NCT01986933 .).