Nemolizumab is Associated with a Rapid Improvement in Atopic Dermatitis Signs and Symptoms: Subpopulation (EASI ≥16) Analysis of Randomized Phase 2B Study.

BACKGROUND Nemolizumab is a humanized anti-IL-31 receptor blocker in phase 3 for atopic dermatitis (AD). OBJECTIVE Analyze onset of action of nemolizumab 30 mg and compare efficacy and safety vs placebo (SC q4wk plus loading dose) in moderate-to-severe AD. METHODS Post-hoc analysis of patients with Eczema Area and Severity Index (EASI) scores ≥16 from a phase 2b trial of moderate-to-severe AD. Endpoints were change in EASI score at week 16, peak pruritus numeric rating scale (PP-NRS), Investigator's Global Assessment (IGA), changes in sleep and responders with ≥4-point improvement on PP-NRS. RESULTS There was a significantly greater itch relief apparent by Day 2 (-22.8% vs -12.3% PP-NRS; P=0.005) which continued to improve through week 16 (-68.5% vs -30.9% PP-NRS; P<0.001). At week 16, PP-NRS ≥4-point response of itch was observed in 68.0% nemolizumab vs 15.9% placebo patients (P≤0.001). There was also a rapid improvement of sleep disturbance with nemolizumab 30 mg, with a significant separation from placebo by day 3 (-26.6% vs -9.0%; P<0.001) which further improved till week 16 (-76.0% vs -36.5%; P<0.001). Also for the EASI score a separation between groups in favor of nemolizumab was observed by week 1 (P≤0.001), which increased through week 16 (-68.6% vs. -42.6%; P=0.002). Finally, the degree of response was greater in nemolizumab-treated patients; clinically relevant reductions of 75% EASI were observed in 50.0% of nemolizumab patients versus 15.9% of placebo patients, while 90% reductions were reported for 36.0% and 6.8% of patients, respectively (P<0.001 for both). IGA success (score of 0/1) was 32.0% for nemolizumab vs 6.8% for placebo (P=0.002). Nemolizumab was safe and well-tolerated in this population; nasopharyngitis and upper respiratory tract infection were the most common adverse events. CONCLUSIONS Nemolizumab resulted in very rapid, sustained improvements of inflammation, pruritus and sleep in patients with EASI ≥16 at baseline.