Targeting IL-31RA with nemolizumab in prurigo nodularis: a systematic review, GRADE-assessed meta-analysis, and trial sequential analysis of randomized controlled trials.

Introduction: Prurigo nodularis (PN) is a chronic, intensely itchy skin condition linked to immune and nerve dysfunction, often affecting individuals with darker skin. It severely impacts quality of life. While traditional treatments are limited, nemolizumab shows promise. However, more diverse and long-term studies are needed to confirm its effectiveness. Methods: This systematic review followed PRISMA 2020 guidelines, analyzing studies on nemolizumab for PN. Data from multiple databases were assessed for efficacy, safety, and bias. Statistical analysis used Review Manager 5.4 with random-effects modeling and heterogeneity evaluation. Results: This meta-analysis included four randomized controlled trials (RCTs) involving 859 participants. Nemolizumab significantly improved Peak Pruritus Numerical Rating Scale (PP-NRS; ≥4 points) in weeks 4 and 16 [risk ratio (RR): 5.87 and 3.52], and PP-NRS <2 (RR: 11.87 and 5.63). It also improved the Sleep Disturbance and Numerical Rationg Scale (SD-NRS) and Investigator's Global Assessment responses. Adverse events were slightly higher (RR: 1.13), though injection reactions, infections, headaches, and gastrointestinal events showed no significant differences. The risk of neurodermatitis was significantly lower with nemolizumab. Trial Sequential Analysis suggests that further large RCTs should be carried out to validate our results. Conclusion: This review confirms nemolizumab as an effective, well-tolerated treatment for PN, providing rapid relief from itching, skin lesions, and sleep issues. With a favorable safety profile, it marks a major advancement in managing this challenging, underserved condition.