Journal Article

Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis

de Bruin-Weller, Marjolein, Fleischer, Alan, Paul, Carle, Physiopathologie des Adaptations Nutritionnelles (PhAN) ; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE) ; Nantes Université - pôle Santé ; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé ; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Nahm, Walter, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Serra-Baldrich, Esther, Szepietowski, Jacek, Laquer, Vivian, University Medical Center [Utrecht] (UMCU), Sauder, Maxwell, Lynde, Charles, Barbarot, Sebastien, Universität Bern = University of Bern = Université de Berne (UNIBE), Conrad, Curdin, Reich, Adam, Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona (UAB), Institut Toulousain des Ma

2023

Overview

Prurigo 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. In 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. A 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%). Nemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.).

• Publisher: Massachusetts Medical Society,CCSD
• Subject: Adult / Allergy / Antibodies, Monoclonal, Humanized / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - therapeutic use / Anxiety / Asthma / Atopic dermatitis / Autoimmune Disease / Clinical Medicine / Clinical Medicine General / Coronaviruses / COVID-19 / Cytokines / Dermatitis, Atopic / Dermatitis, Atopic - chemically induced / Dermatitis, Atopic - etiology / Dermatology / Dermatology General / Double-Blind Method / Edema / Humans / Immunoglobulin A / Immunology / Immunology General / Inflammatory Disease / Life Sciences / Monoclonal antibodies / Neurology / Neurosurgery / Neurosurgery General / Pathophysiology / Patient safety / Placebos / Prurigo / Prurigo - complications / Prurigo - drug therapy / Pruritus / Pruritus - drug therapy / Pruritus - etiology / Quality of life / Receptors, Interleukin / Receptors, Interleukin - antagonists & inhibitors / Severity of Illness Index / Skin / Skin diseases / Sleep / T-Cells / Treatment Outcome