Sonja Ständer1, Gil Yosipovitch1, Franz J Legat1, Jean-Philippe Lacour1, Carle Paul1, Joanna Narbutt1, Thomas Bieber1, Laurent Misery1, Andreas Wollenberg1, Adam Reich1, Faiz Ahmad1, Christophe Piketty1. 1. From the Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster (S.S.), the Department of Dermatology and Allergy, Christine Kühne Center for Allergy Research and Education, University Hospital, Bonn (T.B.), and the Department of Dermatology and Allergy, Ludwig Maximilian University of Munich, Munich (A.W.) - all in Germany; the Itch Center, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Hospital, Miami (G.Y.); the Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria (F.J.L.); the Department of Dermatology, University Hospital of Nice, Nice (J.-P.L.), the Department of Dermatology, University of Toulouse, Toulouse (C. Paul), and the Department of Dermatology, University Hospital of Brest, Brest (L.M.) - all in France; the Department of Dermatology, Medical University of Lodz, Lodz (J.N.), and the Department of Dermatology, University of Rzeszow, Rzeszow (A.R.) - both in Poland; Galderma, Fort Worth, TX (F.A.); and Galderma, Lausanne, Switzerland (C. Piketty).
Abstract
BACKGROUND: Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis. METHODS: We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18. RESULTS:A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms. CONCLUSIONS:Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.).
RCT Entities:
BACKGROUND: Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis. METHODS: We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18. RESULTS: A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms. CONCLUSIONS:Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.).
Authors: Pavel Kolkhir; Daniel Elieh-Ali-Komi; Martin Metz; Frank Siebenhaar; Marcus Maurer Journal: Nat Rev Immunol Date: 2021-10-05 Impact factor: 53.106
Authors: Sherief R Janmohamed; Eran C Gwillim; Muhammad Yousaf; Kevin R Patel; Jonathan I Silverberg Journal: Arch Dermatol Res Date: 2020-10-27 Impact factor: 3.017
Authors: Micah Belzberg; Martin Prince Alphonse; Isabelle Brown; Kyle A Williams; Raveena Khanna; Byron Ho; Shannon Wongvibulsin; Thomas Pritchard; Youkyung Sophie Roh; Nishadh Sutaria; Justin Choi; Jaroslaw Jedrych; Andrew D Johnston; Kakali Sarkar; Chirag Vasavda; Jimmy Meixiong; Carly Dillen; Kent Bondesgaard; John F Paolini; Wei Chen; David Corcoran; Nicolas Devos; Madan M Kwatra; Anna L Chien; Nathan K Archer; Luis A Garza; Xinzhong Dong; Sewon Kang; Shawn G Kwatra Journal: J Invest Dermatol Date: 2021-03-23 Impact factor: 7.590
Authors: Fang Wang; Anna M Trier; Fengxian Li; Seonyoung Kim; Zhen Chen; Jiani N Chai; Madison R Mack; Stephanie A Morrison; Jennifer D Hamilton; Jinok Baek; Ting-Lin B Yang; Aaron M Ver Heul; Amy Z Xu; Zili Xie; Xintong Dong; Masato Kubo; Hongzhen Hu; Chyi-Song Hsieh; Xinzhong Dong; Qin Liu; David J Margolis; Marius Ardeleanu; Mark J Miller; Brian S Kim Journal: Cell Date: 2021-01-14 Impact factor: 66.850
Authors: Jianghui Meng; Yanqing Li; Michael J M Fischer; Martin Steinhoff; Weiwei Chen; Jiafu Wang Journal: Front Immunol Date: 2021-06-30 Impact factor: 7.561