Monthly subcutaneous injections of nemolizumab, a humanized monoclonal antibody that inhibits interleukin-31 signaling, significantly improved pruritus associated with atopic dermatitis (AD) in a small, 3-month phase II trial. The results were published online March 2 in the New England Journal of Medicine.
“Although this trial has limitations, most notably the small number of patients and short duration, it provides evidence supporting the role of interleukin-31 in the pathobiologic mechanism of atopic dermatitis,” said Thomas Ruzicka, MD, of the department of dermatology and allergology, Ludwig Maximilian University, Munich, and his associates.
Pruritus aggravates atopic dermatitis and has been linked to loss of sleep, depression, aggressiveness, body disfiguration, and suicidal thoughts. Existing treatments, including emollients, topical glucocorticoids, calcineurin inhibitors, and oral antihistamines, have limited efficacy and can cause adverse effects when used long term, the investigators noted.
They assessed nemolizumab in a manufacturer-funded multiple-dose trial involving 264 adults in the United States, Europe, and Japan who had refractory moderate to severe atopic dermatitis, inadequately controlled with topical treatments. Study participants were randomly assigned in a double blind fashion to receive 12 weeks of 0.1 mg/kg nemolizumab (53 patients), 0.5 mg/kg nemolizumab (54 patients), 2.0 mg/kg nemolizumab (52 patients), or placebo (53 control subjects) every 4 weeks. Another 52 participants were given 2.0 mg/kg nemolizumab every 8 weeks in an exploratory analysis. All the study participants were permitted to use emollients and localized treatments, and some were permitted by the investigators to use a potent topical glucocorticoid as rescue therapy after week 4.
A total of 216 patients (82%) completed the trial.
The primary efficacy endpoint was the percentage improvement at week 12 in scores on a pruritus visual analogue scale, which patients recorded electronically every day. These scores improved significantly in a dose-dependent manner for active treatment, compared with placebo. Pruritus declined by 43.7% with the 0.1 mg/kg dose (P =.002), 59.8% with the 0.5 mg/kg dose (P less than .001), and 63.1% with the 2.0 mg/kg dose (P less than .001), compared with 20.9% with placebo.
Nemolizumab also bested placebo in several secondary endpoints including scores on a verbal rating of pruritus, the Eczema Area and Severity Index, and the static Investigator’s Global Assessment, the investigators said (N Engl J Med 2017;376:826-35. doi: 10.1056/NEJMoa1606490).
The study population was too small to allow the investigators to draw conclusions regarding adverse events, even before a relatively high number of participants dropped out. However, patients who received active treatment had a higher rate of dermatitis exacerbations and peripheral edema than did those who received placebo.
The group given 0.5 mg/kg nemolizumab every month showed the greatest treatment benefit and the best benefit-to-risk profile, Dr. Ruzicka and his associates said.
This trial was funded by Chugai Pharmaceutical, which also participated in the study design, data collection and analysis, and preparation of the manuscript. Dr. Ruzicka reported receiving research grants and personal fees from Chugai and honoraria from Astellas; his associates reported ties to numerous industry sources.