Nemolizumab Demonstrates Strong Efficacy in PN

The relentless itch-scratch cycle of prurigo nodularis (PN) leads to skin damage, inflammation, and significant psychosocial burden, including sleep disruption and emotional distress. Although the pathogenesis of PN remains incompletely understood, growing evidence implicates a dysregulated neuroimmune interface involving interleukin-31 (IL-31)–mediated signaling. Current therapies, such as topical corticosteroids, systemic immunosuppressants, and phototherapy, primarily address inflammation but fail to target the underlying mechanisms of pruritus.¹

Nemolizumab, a humanized monoclonal antibody targeting the IL-31 receptor A (IL-31RA), has emerged as a novel therapeutic agent capable of addressing both the inflammatory and neural components of PN. A recent meta-analysis synthesized evidence from randomized controlled trials (RCTs) evaluating nemolizumab’s efficacy and safety in PN, providing the most comprehensive evaluation of this therapy to date.²

Methods

A comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science identified clinical studies evaluating nemolizumab in PN patients, with no language or publication date restrictions. Additional searches of clinical trial registries and reference lists supplemented the database search.

Two independent reviewers screened records, assessed full texts, and extracted relevant data, including study characteristics, treatment regimens, and clinical outcomes. Eligible studies were randomized controlled trials evaluating nemolizumab versus placebo in adults with moderate to severe PN. Outcomes of interest included reduction in pruritus, defined as a ≥4-point decrease in the Worst Itch Numeric Rating Scale (WI-NRS), and skin improvement, assessed by Investigator’s Global Assessment (IGA) success (score of 0 or 1 with ≥2-grade improvement from baseline). Treatment-emergent adverse events (AEs) were analyzed to assess safety.

Results

The initial search identified 658 records, of which 4 RCTs met inclusion criteria following screening and full-text review. These studies, published between 2020 and 2024, collectively enrolled 859 participants with moderate to severe PN. Study durations ranged from 11 to 32 weeks.

Efficacy Outcomes
Across the 4 trials, researchers found nemolizumab demonstrated a significant improvement in pruritus. Pooled analysis revealed that patients receiving nemolizumab were 3.52 times more likely to achieve meaningful itch reduction compared with placebo (RR 3.52; 95% CI: 2.48–5.02; p < 0.00001). Heterogeneity was low (I² = 28%), suggesting consistent treatment effects across studies.

Similarly, nemolizumab was associated with significant improvements in overall skin clearance. The pooled RR for achieving IGA success was 4.40 (95% CI: 2.86–6.75; p < 0.00001), with low heterogeneity (I² = 11%). Individual study results consistently favored nemolizumab, with RRs ranging from 3.43 to 10.27.

Safety Outcomes
Adverse events occurred at similar rates between nemolizumab and control groups. The pooled RR for treatment-emergent AEs was 1.11 (95% CI: 0.99–1.24; p = 0.84), indicating no statistically significant difference. Reported AEs were mostly mild to moderate, with no new safety signals identified.

Discussion

This meta-analysis provides robust evidence supporting nemolizumab as an effective therapy for moderate to severe PN. The drug’s mechanism, blocking IL-31RA, interrupts the pruritic and inflammatory signaling cascade central to PN pathogenesis. By inhibiting IL-31–driven activation of sensory neurons and keratinocytes, nemolizumab addresses the dual neuroimmune basis of pruritus and lesion formation.

These findings align with prior mechanistic studies demonstrating suppression of cutaneous nerve activity markers and inflammatory pathways following IL-31RA inhibition. The consistent clinical efficacy observed across studies underscores IL-31’s pivotal role in PN’s pathophysiology.

Although nemolizumab’s short-term safety profile appears favorable, mild events such as peripheral edema and nasopharyngitis have been reported. Isolated cases of asthma and atopic dermatitis occurred more frequently in treated patients, echoing observations from trials in atopic dermatitis. Importantly, long-term safety data remain limited; the ongoing 192-week OLYMPIA LTE trial aims to further characterize the durability and tolerability of treatment.

Study Limitations

While findings are encouraging, the meta-analysis included only 4 RCTs with relatively short follow-up durations (up to 32 weeks). The small number of trials limits subgroup analyses and long-term safety evaluation. Moreover, the lack of data on disease severity stratification or comorbidities precludes a nuanced understanding of which patients derive the greatest benefit.

Future studies should aim for longer observation periods, larger and more diverse populations, and standardized endpoints to validate these findings and establish nemolizumab’s place in therapy relative to other biologics, such as dupilumab.

Conclusion

This comprehensive meta-analysis of randomized controlled trials demonstrates that nemolizumab significantly improves pruritus and skin clearance in patients with moderate to severe PN, with a favorable short-term safety profile. While these results mark an important advance in PN management, further long-term research is warranted to clarify sustained efficacy, safety, and optimal integration into clinical practice.

Nemolizumab’s success highlights the therapeutic potential of targeting the IL-31 signaling pathway—offering new hope for patients burdened by the chronic itch and disfigurement of PN.

References

1. Kwatra SG, Pereira MP, Misery L, Mollanazar NK, Shah P, Wiggins S. Prurigo nodularis: disease burden, clinical features and approach to management. Br J Dermatol. 2025;193(4):642-652. doi:10.1093/bjd/ljaf213
2. Sinha K, Sinha T, Muppa N, et al. Efficacy and safety of nemolizumab in patients with prurigo nodularis: A systematic review and meta-analysis of randomized controlled trials. Cureus. 2025;17(2):e78761. Published 2025 Feb 9. doi:10.7759/cureus.78761