• Shawn G Kwatra, Gil Yosipovitch, Franz J Legat, Adam Reich, Carle Paul, Dagmar Simon, Luigi Naldi, Charles Lynde, Marjolein S De Bruin-Weller, Walter K Nahm, Maxwell Sauder, Rola Gharib, Sebastien Barbarot, Jacek C Szepietowski, Curdin Conrad, Alan Fleischer, Vivian T Laquer, Laurent Misery, Esther Serra-Baldrich, Hilde Lapeere, Faiz Ahmad, Zarif K Jabbar Lopez, Christophe Piketty, Sonja Ständer, and OLYMPIA 2 Investigators.
• From Johns Hopkins Itch Center, Johns Hopkins University School of Medicine, Baltimore (S.G.K.); the Miami Itch Center, Miller School of Medicine at the University of Miami, Miami (G.Y.); the Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria (F.J.L.); the Department of Dermatology, University of Rzeszow, Rzeszow (A.R.), and the Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw (J.C.S.) - both in Poland; the Department of Dermatology, Medical University of Toulouse, Toulouse (C.P.), the Department of Dermatology, University Hospital, Nantes (S.B.), and the Department of Dermatology, University Hospital of Brest, Brest (L.M.) - all in France; the Department of Dermatology, Bern University Hospital, Bern (D.S.), the Department of Dermatology, Lausanne University Hospital CHUV and University of Lausanne, Lausanne, (C.C.), and Galderma, Zug (Z.K.J.L., C.P.) - all in Switzerland; the Academic Research Center, Centro Studi GISED, Bergamo, Italy (L.N.); the Lynde Institute for Dermatology & Lynderm Research and the Division of Dermatology, Department of Medicine (C.L.), University of Toronto, Toronto (C.L., M.S.); the Department of Dermatology and Allergology, Utrecht University-UMC, Utrecht, the Netherlands (M.S.D.B.-W.); the University Dermatology Group, University of California, San Diego, San Diego (W.K.N.), and First OC Dermatology Research, Fountain Valley (V.T.L.) - both in California; West Virginia Research Institute, Morgantown (R.G.); the Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati (A.F.); Hospital de la Santa Creu i Sant Pau, Barcelona (E.S-B.); the Department of Dermatology, Ghent University Hospital, Ghent, Belgium (H.L.); Galderma R&D, Dallas (F.A.); and the Center for Chronic Pruritus, University Hospital, Munster, Germany (S.S.).
• N. Engl. J. Med. 2023 Oct 26; 389 (17): 157915891579-1589.

BackgroundPrurigo nodularis is a chronic, debilitating, and severely pruritic neuroimmunologic skin disease. Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis.MethodsIn this phase 3, double-blind, multicenter, randomized trial, we assigned adults with moderate-to-severe prurigo nodularis to receive an initial 60-mg dose of nemolizumab followed by subcutaneous injections of 30 mg or 60 mg (depending on baseline weight) every 4 weeks for 16 weeks or matching placebo. The primary end points were an itch response (a reduction of ≥4 points on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10, with higher scores indicating more severe itch]) and an Investigator's Global Assessment (IGA) response (a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4] and a reduction from baseline to week 16 of ≥2 points). There were five key secondary end points.ResultsA total of 274 patients underwent randomization; 183 were assigned to the nemolizumab group, and 91 to the placebo group. Treatment efficacy was shown with respect to both primary end points at week 16; a greater percentage of patients in the nemolizumab group than in the placebo group had an itch response (56.3% vs. 20.9%; strata-adjusted difference, 37.4 percentage points; 95% confidence interval [CI], 26.3 to 48.5), and a greater percentage in the nemolizumab group had an IGA response (37.7% vs. 11.0%; strata-adjusted difference, 28.5 percentage points; 95% CI, 18.8 to 38.2) (P<0.001 for both comparisons). Benefits were observed for the five key secondary end points: itch response at week 4 (41.0% vs. 7.7%), PP-NRS score of less than 2 at week 4 (19.7% vs. 2.2%) and week 16 (35.0% vs. 7.7%), and an improvement of 4 or more points on the sleep disturbance numerical rating scale (range, 0 [no sleep loss] to 10 [unable to sleep at all]) at week 4 (37.2% vs. 9.9%) and week 16 (51.9% vs. 20.9%) (P<0.001 for all comparisons). The most common individual adverse events were headache (6.6% vs. 4.4%) and atopic dermatitis (5.5% vs. 0%).ConclusionsNemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.).Copyright © 2023 Massachusetts Medical Society.

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