Abstract
BACKGROUND/OBJECTIVES: Itch is the most burdensome symptom in atopic dermatitis (AD) and prurigo nodularis (PN) and is associated with significant psychological distress, sleep deprivation and impaired quality of life. Achieving rapid control of itch is expected to minimize symptomatology and disease burden. Nemolizumab, which targets the interleukin 31 (IL-31) pathway, rapidly relieved itch in Phase 2 trials; thus, a post hoc analysis of four pivotal randomized controlled clinical trials of nemolizumab in AD and PN was performed to further evaluate the improvement of itch over the first 14 days of therapy. METHODS: Data from ARCADIA 1 and 2 in AD (N = 1728) and OLYMPIA 1 and 2 in PN (N = 560) were analysed. Patients reported itch intensity and sleep disturbance daily. Differences in the proportion of itch and sleep responders (patients with ≥4-point improvement from baseline in peak pruritus numerical rating scale [PP-NRS] or sleep disturbance [SD-NRS] score) between nemolizumab and placebo groups were calculated. RESULTS: Nemolizumab rapidly reduced itch in AD (ARCADIA 1 and 2), with a difference versus placebo in PP-NRS responders apparent by Day 2 (pooled data: 10.7% vs. 2.9%; 95% CI: 5.6-10.1; p < 0.0001) that steadily increased through Day 14. Nemolizumab also reduced itch rapidly in PN (OLYMPIA 1 and 2); a difference versus placebo occurred by Day 2 (pooled data: 17.2% vs. 3.7%; 95% CI: 6.8-16.7; p < 0.0001). Early improvement (Day 2) was also observed in sleep in nemolizumab-treated patients. In pooled analyses in AD, 9.9% (nemolizumab) versus 4.6% (placebo; 95% CI: 2.8-7.7; p = 0.0001) were SD-NRS responders and in PN, 13.4% versus 4.3% (95% CI: 4.0-13.0; p = 0.0013). Itch and sleep response data in individual studies were consistent with the pooled data. CONCLUSIONS: This analysis confirms previously reported data that nemolizumab relieves itch and sleep disturbance by Day 2 in patients with moderate-to-severe AD and PN, indicating that targeting the IL-31 pathway presents an important way to achieve rapid itch response.