Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis
Por:
Kwatra, SG, Yosipovitch, G, Legat, FJ, Reich, A, Paul, C, Simon, D, Naldi, L, Lynde, C, De Bruin-Weller, MS, Nahm, WK, Sauder, M, Gharib, R, Barbarot, S, Szepietowski, JC, Conrad, C, Fleischer, A, Laquer, VT, Misery, L, Serra-Baldrich, E, Lapeere, H, Ahmad, F, Lopez, ZKJ, Piketty, C, Ständer, S
Publicada:
26 oct 2023
Resumen:
Background 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.Methods 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.Results 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%).Conclusions Nemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.)
Filiaciones:
Kwatra, SG:
Johns Hopkins Univ, Johns Hopkins Itch Ctr, Sch Med, Baltimore, MD USA
Yosipovitch, G:
Univ Miami, Miami Itch Ctr, Miller Sch Med, Miami, FL USA
Legat, FJ:
Med Univ Graz, Dept Dermatol & Venereol, Graz, Austria
Reich, A:
Univ Rzeszow, Dept Dermatol, Rzeszow, Poland
Paul, C:
Med Univ Toulouse, Dept Dermatol, Toulouse, France
Simon, D:
Bern Univ Hosp, Dept Dermatol, Bern, Switzerland
Naldi, L:
Ctr Studi GISED, Acad Res Ctr, Bergamo, Italy
Lynde, C:
Univ Toronto, Lynde Inst Dermatol & Lynderm Res, Toronto, ON, Canada
Univ Toronto, Dept Med, Div Dermatol, Toronto, ON, Canada
Univ Toronto, Toronto, ON, Canada
De Bruin-Weller, MS:
Utrecht Univ UMC, Dept Dermatol & Allergol, Utrecht, Netherlands
Nahm, WK:
Univ Calif San Diego, Univ Dermatol Grp, San Diego, CA USA
Sauder, M:
Univ Toronto, Toronto, ON, Canada
Gharib, R:
West Virginia Res Inst, Morgantown, WV USA
Barbarot, S:
Univ Hosp, Dept Dermatol, Nantes, France
Szepietowski, JC:
Wroclaw Med Univ, Dept Dermatol Venereol & Allergol, Wroclaw, Poland
Conrad, C:
Lausanne Univ Hosp CHUV, Dept Dermatol, Lausanne, Switzerland
Univ Lausanne, Lausanne, Switzerland
Fleischer, A:
Univ Cincinnati, Coll Med, Dept Dermatol, Cincinnati, OH USA
Laquer, VT:
First OC Dermatol Res, Fountain Valley, CA USA
Misery, L:
Univ Hosp Brest, Dept Dermatol, Brest, France
Serra-Baldrich, E:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Lapeere, H:
Ghent Univ Hosp, Dept Dermatol, Ghent, Belgium
Ahmad, F:
Galderma R&D, Dallas, TX USA
Lopez, ZKJ:
Galderma, Zahlerweg 10, CH-6300 Zug, Switzerland
Piketty, C:
Galderma, Zahlerweg 10, CH-6300 Zug, Switzerland
Ständer, S:
Univ Hosp, Ctr Chron Pruritus, Munster, Germany
|