Prurigo nodularis (PN) is a subtype of chronic prurigo that is highly pruritic, chronic, difficult to treat and associated with high disease burden. [1] The pathogenesis of PN is not completely understood, although inflammatory pathways have strongly implicated the involvement of IL-31. [2] Nemolizumab is a humanised monoclonal antibody targeting the IL-31 receptor alpha subunit that is under development for treatment of severe pruritic skin diseases.

• This phase II study investigated the efficacy and safety of nemolizumab in moderate-to-severe PN and associated severe pruritus.

Type of study, patients, and inclusion criteria

• Multicentre (20 sites, EU), randomised, double-blinded, placebo-controlled, parallel group study.
• Patients had to have had a clinical diagnosis of PN for at least 6 months, with least 20 nodules on the body with bilateral distribution and severe pruritus (NRS (Numerical Rating Scale) ≥7).
• A total of 70 patients were randomised to placebo (N=36) or nemolizumab (N=34).

Primary outcome measure

• The primary endpoint was percent reduction from baseline in peak pruritus NRS at week 4.

• Overall, baseline characteristics were similar between groups.
• Changes in the primary endpoint, percent change in peak pruritus NRS, were significant within week 1 and remained significant at all time points thereafter.
• The absolute change in peak pruritus NRS at week 12 was-5.2 for nemolizumab vs -1.7 for placebo; P ≤0.001.
• 4-point peak pruritus NRS responder rate at week 12 was 52.9% for nemolizumab vs 8.3% for placebo: Δ-44.6, P <0.001; ITT (Figure).
• There was no difference in peak pruritus between patients with and without atopic predisposition.
• At week 18, significantly more patients reached IGA success with nemolizumab (44.1% than with placebo (5.6%; P = 0.001).
• At week 18, significantly more patients achieved PASI75 with nemolizumab (38.2% than with placebo (8.4%; P <0.001).
• Nemolizumab was also associated with significant improvement in sleep disturbance from baseline vs placebo.
• In the nemolizumab group 5.9% of patients discontinued the study medication for an adverse event vs 5.6% for placebo.
• Overall, the adverse event profile was similar between groups.

• Nemolizumab resulted in a rapid and clinically relevant improvement of pruritus and nodular lesions in PN with onset of effect on pruritus as early as week 1 with 38% of patients clear or almost clear of skin lesions.
• Nemolizumab was significantly more effective than placebo in all clinical endpoints
• Nemolizumab was well tolerated with a similar safety profile vs placebo.