Title : Efficacy and safety of nemolizumab in patients with prurigo nodularis: A systematic review and meta-analysis of randomized controlled trials
Abstract:
Introduction: Prurigo nodularis (PN) is a chronic, intensely pruritic dermatologic condition characterized by hyperkeratotic nodules that significantly impair quality of life. Recent advances have highlighted the role of interleukin-31 in PN pathogenesis, positioning nemolizumab, an IL31 receptor A antagonist, as a potential targeted therapy. This systematic review and metaanalysis aimed to evaluate the efficacy and safety of nemolizumab in patients with PN based on randomized controlled trials (RCTs).
Methodology: A comprehensive search of Medline (via PubMed), Web of Science, Scopus, Embase, and Cochrane databases was conducted through 2025. RCTs evaluating nemolizumab in PN patients were included. Two independent reviewers screened titles, abstracts, and full texts, and extracted relevant data. The Cochrane Risk of Bias tool (ROB-2) was used to assess study quality. Meta-analyses were performed using a random-effects model, and results were expressed as risk ratios (RRs) with 95% confidence intervals (CIs).
Results: Four RCTs published between 2020 and 2025 met inclusion criteria, encompassing 859 participants (560 in the nemolizumab group, 299 in the placebo group). The mean age ranged from 50 to 57 years. Studies were conducted in Switzerland, France, Japan, and a multicenter trial across nine countries. All studies were deemed to have a low risk of bias.
Efficacy: Nemolizumab demonstrated superior efficacy compared to placebo: PP-NRS improvement ≥4 points: Significant improvement at week 4 (RR: 5.87, 95% CI: [3.42–10.05]) and week 16 (RR: 3.52, 95% CI: [1.91–6.5]); I² = 0%.
PP-NRS <2: Achieved more frequently with nemolizumab at week 4 (RR: 11.87, 95% CI: [3.79–37.18]) and week 16 (RR: 5.63, 95% CI: [3.12–10.16]); I² = 0%.
Sleep disturbance NRS (SD-NRS) improvement ≥4 points: Significant at week 4 (RR: 4.42, 95% CI: [2.62–7.45]) and week 16 (RR: 3.04, 95% CI: [2.23–4.15]); low heterogeneity.
Investigator’s Global Assessment response: Improved response at weeks 12–16 (RR: 4.06, 95% CI: [2.42–6.8]); I² = 0%. Adverse events were slightly higher with nemolizumab (RR: 1.13, 95% CI: [1.01–1.26], p = 0.04); however, injection-site reactions (RR: 3.35, p = 0.18), infections (RR: 0.86, p = 0.36), nasopharyngitis (RR: 0.87, p = 0.69), gastrointestinal events (RR: 1.27, p = 0.52), and headache (RR: 1.75, p = 0.19) did not significantly differ between groups. Notably, the risk of neurodermatitis or atopic dermatitis was lower with nemolizumab (RR: 0.66, 95% CI: [0.46–0.95], p = 0.02).
Conclusion: Nemolizumab is an effective and generally well-tolerated treatment for prurigo nodularis, significantly improving pruritus severity, sleep quality, and global assessment scores. While there is a modest increase in adverse events, the safety profile remains acceptable. These findings support nemolizumab as a promising therapy for PN; however, further long-term studies are warranted to confirm durability and safety.
