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Prurigo nodularis (PN) or chronic nodular prurigo is a debilitating, and severely pruritic neuroimmune skin disease, predominantly characterized by the presence of multiple pruriginous nodules symmetrically distributed in large areas of the trunk and extremities. Other pruriginous lesions such as papules, plaques and umbilicated lesions can also be present. Prurigo nodularis dramatically reduces quality of life among patients, including disruption of physical, emotional and psychosocial domains. Therapeutic goals are primarily to reduce pruritus and improve lesion healing. Interleukin-31 (IL-31) is a neuroimmune cytokine highly expressed in PN lesional skin that bridges the immune and nervous systems, functioning as a central mediator of main pathophysiological processes in PN. Prurigo nodularis has a unique immunophenotype, with recent studies revealing activation of Type-2-inflammation, and also induction of Th17 and Th22 pathways. Nemolizumab, an IL-31 receptor alpha antagonist, was shown to downregulate these pathways and was associated with significant improvements in pruritus and lesion healing in patients with PN in a phase-2-trial. Here, the authors report additional outcomes on excoriations and healing of pruriginous lesions from the OLYMPIA 2 phase-3-study after 16 weeks of treatment with nemolizumab. This study aims to assess the safety and efficacy of nemolizumab compared with placebo in ≥18-year-old patients with moderate-to-severe PN after a 16-week treatment period. OLYMPIA 2 (NCT04501679) was a phase 3, global, multicenter, double-blind study in adults with PN presenting ≥20 nodules, Investigator's Global Assessment (IGA) score ≥3 (range 0–4) and Peak Pruritus Numerical Rating Scale (PP-NRS) score ≥7.0 (range: 0–10). Patients were randomized (2 : 1) to receive nemolizumab (n = 183) or matching placebo (n = 91). Following an initial 60 mg loading dose, patients weighing <90 kg received 30 mg every 4 weeks (q4w) and those weighing ≥90 kg received 60 mg q4w, for a period of 16 weeks, during which, treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI)was not allowed. The primary endpoints were proportion of patients with a ≥4-point improvement in weekly average PP-NRS and proportion of patients with IGA Success for nodule healing [score of 0 (clear) or 1 (almost clear) and a ≥2-grade improvement] at Week (W) 16. Key secondary endpoints included proportion of patients with ≥4-point improvement in PP-NRS at W4 and Sleep Disturbance NRS (SD-NRS) at W4 and W16. Other secondary endpoints included percentage of patients with pruriginous lesions with excoriations/crusts [Prurigo activity score (PAS) item 5a], healed pruriginous lesions (PAS item 5b) and <20 pruriginous lesions (PAS item 2) at each visit through W16. The baseline demographic and clinical characteristics were balanced between the groups. At W16, both primary endpoints, were met (P < 0.0001). A significantly higher proportion of patients in the nemolizumab-treated group vs. placebo-treated group achieved a ≥4-point improvement in weekly average PP-NRS score (56.3% vs. 20.9%) and IGA success (37.7% vs. 11.0%) at W16. The study also met all key secondary endpoints on pruritus and sleep disturbance (P < 0.0001). Among other secondary endpoints, a significantly higher proportion of patients in the nemolizumab-treated group vs. placebo-treated group achieved mild disease activity with ≤25% excoriations/crusts (PAS item 5a) (56.8% vs. 23.1%; P < 0.0001 at W16), >75% healed lesions (PAS item 5b) (55.2% vs. 16.5%; P < 0.0001 at W16) and <20 pruriginous lesions (PAS item 2) (54.6% vs. 22.0%; P < 0.0001 at W16) at each visit, from baseline through W16. Treatment-emergent adverse events (AEs) were reported in 61.2% of nemolizumab-treated patients and 52.7% of placebo-treated patients, while serious AEs were reported in 2.2% of nemolizumab-treated patients and 5.5% of placebo-treated patients. Nemolizumab monotherapy (without TCS or TCI) demonstrated a significant reduction of pruritus as well as excoriations and number of pruriginous lesions after 16 weeks of treatment in patients with moderate-to-severe PN. The safety profile was consistent with that previously observed. [ABSTRACT FROM AUTHOR]