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