Efficacy and Safety of Nemolizumab in Patients With Moderate to Severe Prurigo Nodularis
Authors: Ständer Sonja , Yosipovitch Gil , Legat Franz J. , Reich Adam , Paul Carle , Simon Dagmar , Naldi Luigi , Metz Martin , Tsianakas Athanasios , Pink Andrew , Fage Simon , Micali Giuseppe , Weisshaar Elke , Sundaram Hema , Metelitsa Andrei , Augustin Matthias , Wollenberg Andreas , Homey Bernhard , Fargnoli Maria Concetta , Sofen Howard , Korman Neil J. , Skov Lone , Chen Xiaoxiao , Jabbar-Lopez Zarif K. , Piketty Christophe , Kwatra Shawn G. ,   OLYMPIA 1 Investigators, Sepp Norbert , Holzer Gregor , Guenther Lyn C.C. , Walker Kirsten Ann , Podda Maurizio , Ruëff Franziska , Volc Sebastien , Yazdi Amir , Goebeler Matthias , Sticherling Michael , Herzog Rebeca , Buhl Timo , Thaçi Diamant , Zink Alexander , Wohlrab Johannes , Maintz Laura , Staubach-Renz Petra , Reich Kristian , Weisshaar Elke , Gerdes Sascha , Patsinakidis Nikolaos , Lajos Kemeny , Almadi Tamas , Toth Mariann , Fekete Aniko Maria Dobribanne , Feliciani Claudio , Peris Ketty , Amerio Paolo , Lasagni Claudia , Parodi Aurora , Cristaudo Antonio , Argenziano Guiseppe , Stingeni Luca , Kolodziej Tomasz , Galus Ryszard , Zakrzewski Marcin , Wolnik-Trzeciak Grazyna , Renczynska-Matysko Joanna , Slugocki Rafal , Sieniawska Joanna , Janowicz Anna , Kuzmina Natalia , Ladoyanni Evmorfia , Meggitt Simon Jon , Beattie Paula , Muglia Jennie J. , Elewski Boni E. , Draelos Zoe Diana , Primka Edward J. , Lam Yaohan Adrienne , Anadkat Milan J. , Parish Jennifer L. , Gordon Kathleen Pieroni , Fuxench Zelma C. Chiesa , Stone Melody L. , Zook Matthew Brent , Yamauchi Paul Steven , Teller Craig , Lane Joshua , Woseth Douglas M. , Pedrozo Alejandro , Ling Mark Russell , Snyder Robert A. , Helfrich Yolanda , Cohen David , Weiss Eduardo T. , Plotkin Adam , Groysman Vlada , Krishna Sheila , Gadzia Joseph E. , Caban Francis , Holmes Faith L. , Goldman Mitchel , Sivamani Raja 
Published: November 2024

ImportancePrurigo nodularis (PN) is a chronic and debilitating skin condition, characterized by intense itch with multiple nodular lesions. Nemolizumab demonstrated significant improvements in itch and skin nodules in adults with moderate to severe PN in a previous 16-week phase 3 study (OLYMPIA 2).ObjectiveTo assess the efficacy and occurrence of adverse events in adults with moderate to severe PN treated with nemolizumab vs those receiving placebo.Design, Setting, and ParticipantsOLYMPIA 1 was a multicenter, placebo-controlled, phase 3 randomized clinical trial, conducted from August 2020 to March 2023 at 77 centers across 10 countries in adults with moderate to severe PN (at least 20 nodules and an Investigator’s Global Assessment [IGA] score ≥3) and Peak Pruritus Numerical Rating Scale (PP-NRS) score of at least 7.0; consisted of screening (up to 4 weeks), 24-week treatment, and 8-week follow-up periods.InterventionsPatients were randomized (2:1) to nemolizumab monotherapy, 30 mg or 60 mg (depending on baseline weight of less than 90 kg vs 90 kg or greater, respectively), or matching placebo administered every 4 weeks for 24 weeks.Main Outcomes and MeasuresThe primary end points were the proportion of patients with itch response (≥4-point improvement from baseline in weekly average PP-NRS) and IGA success (score of 0/1 [clear/almost clear] and 2-grade or more improvement from baseline) at week 16.ResultsOf 286 patients (mean [SD] age, 57.5 [13.0] years; mean [SD] body weight, 85.0 [20.7] kg; 166 [58.0%] female), 190 were randomized to receive nemolizumab, and 96 were randomized to placebo. A significantly greater proportion of patients assigned to nemolizumab vs placebo achieved itch response (111/190 [58.4%] vs 16/96 [16.7%]; Δ, 40.1% [95% CI, 29.4%-50.8%]; P &amp;lt; .001) and IGA success (50/190 [26.3%] vs 7/96 [7.3%]; Δ, 14.6% [95% CI, 6.7%-22.6%]; P = .003) at week 16. At week 24, the proportion of patients with itch response was 58.3% vs 20.4% (Δ, 38.7% [95% CI, 27.5%-49.9%]) in the ad hoc analysis, and IGA success was 58/190 (30.5%) vs 9/96 (9.4%) (Δ, 19.2% [95% CI, 10.3%-28.1%]) in the nemolizumab-treated vs placebo group. During the treatment period, 134 patients (71.7%) receiving nemolizumab vs 62 patients (65.3%) receiving placebo had at least 1 adverse event; most events were of mild to moderate severity.Conclusions and RelevanceIn this randomized clinical trial, nemolizumab monotherapy led to clinically meaningful and statistically significant improvements in core signs and symptoms of PN.Trial RegistrationClinicalTrials.gov Identifier: NCT04501666