Jonathan I Silverberg1, Andreas Pinter2, Grazyna Pulka3, Yves Poulin4, Jean-David Bouaziz5, Andreas Wollenberg6, Dédée F Murrell7, Andrew Alexis8, Lisa Lindsey9, Faiz Ahmad9, Christophe Piketty10, Alan Clucas11. 1. Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Ill. Electronic address: jonathanisilverberg@gmail.com. 2. Department of Dermatology, Venereology, and Allergology, Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany. 3. School of Medicine, Jagiellonian University Medical College, Krakow, Poland. 4. Department of Medicine, Université Laval, Quebec City, Quebec, Canada. 5. Department of Dermatology, Paris VII Sorbonne Paris Cité University Assistance Publique-Hôpitaux de Paris, Paris, France. 6. Department of Dermatology and Allergology, Ludwig-Maximilians-Universität, Munich, Germany. 7. Department of Dermatology, St George Clinical School, University of New South Wales, Sydney, Australia. 8. Department of Dermatology, Icahn School of Medicine, Mount Sinai, New York, NY. 9. Galderma Laboratories, Fort Worth, Tex. 10. Galderma R&D, Lausanne, Switzerland. 11. Retired, Sophia Antipolis, France.
Abstract
BACKGROUND:Nemolizumab targets the IL-31 receptor α subunit involved in atopic dermatitis (AD) pathogenesis. OBJECTIVE: We sought to evaluate a new dosing strategy of nemolizumab in patients with AD. METHODS: We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90 mg) subcutaneous injections every 4 weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control with topical treatment (n = 226). The Eczema Area and Severity Index (EASI), the peak pruritus (PP) numeric rating scale (NRS), and the Investigator's Global Assessment (IGA) were assessed. Standard safety assessments were performed. RESULTS:Nemolizumab improved EASI, IGA, and/or NRS-itch scores, with the 30-mg dose being most effective. Nemolizumab (30 mg) reduced EASI scores versus placebo at week 24 (-68.8% vs -52.1%, P = .016); significant differences were observed by week 8 (P ≤ .01). With significant improvement (P = .028) as early as week 4, IGA 0/1 rates were higher for 30 mg of nemolizumab versus placebo at week 16 (33.3% vs 12.3%, P = .008) but not week 24 because of an increased placebo/topical corticosteroid effect (36.8% vs 21.1%, P = .06). PP-NRS scores were improved for 30 mg of nemolizumab versus placebo at week 16 (-68.6% vs -34.3%, P < .0001) and week 24 (-67.3% vs -35.8%, P < .0001), with a difference by week 1 (P < .001). NRS response rates (≥4-point decrease) were greater for 30 mg of nemolizumab versus placebo at week 16 (P ≤ .001) and week 24 (P ≤ .01). Nemolizumab was safe and well tolerated. The most common adverse events were nasopharyngitis and upper respiratory tract infection. CONCLUSIONS:Nemolizumab resulted in rapid and sustained improvements in cutaneous signs of inflammation and pruritus in patients with AD, with maximal efficacy observed at 30 mg. Nemolizumab had an acceptable safety profile.
RCT Entities:
BACKGROUND:Nemolizumab targets the IL-31 receptor α subunit involved in atopic dermatitis (AD) pathogenesis. OBJECTIVE: We sought to evaluate a new dosing strategy of nemolizumab in patients with AD. METHODS: We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90 mg) subcutaneous injections every 4 weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control with topical treatment (n = 226). The Eczema Area and Severity Index (EASI), the peak pruritus (PP) numeric rating scale (NRS), and the Investigator's Global Assessment (IGA) were assessed. Standard safety assessments were performed. RESULTS:Nemolizumab improved EASI, IGA, and/or NRS-itch scores, with the 30-mg dose being most effective. Nemolizumab (30 mg) reduced EASI scores versus placebo at week 24 (-68.8% vs -52.1%, P = .016); significant differences were observed by week 8 (P ≤ .01). With significant improvement (P = .028) as early as week 4, IGA 0/1 rates were higher for 30 mg of nemolizumab versus placebo at week 16 (33.3% vs 12.3%, P = .008) but not week 24 because of an increased placebo/topical corticosteroid effect (36.8% vs 21.1%, P = .06). PP-NRS scores were improved for 30 mg of nemolizumab versus placebo at week 16 (-68.6% vs -34.3%, P < .0001) and week 24 (-67.3% vs -35.8%, P < .0001), with a difference by week 1 (P < .001). NRS response rates (≥4-point decrease) were greater for 30 mg of nemolizumab versus placebo at week 16 (P ≤ .001) and week 24 (P ≤ .01). Nemolizumab was safe and well tolerated. The most common adverse events were nasopharyngitis and upper respiratory tract infection. CONCLUSIONS:Nemolizumab resulted in rapid and sustained improvements in cutaneous signs of inflammation and pruritus in patients with AD, with maximal efficacy observed at 30 mg. Nemolizumab had an acceptable safety profile.
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: Thanaporn Ratchataswan; Tina M Banzon; Jacob P Thyssen; Stephan Weidinger; Emma Guttman-Yassky; Wanda Phipatanakul Journal: J Allergy Clin Immunol Pract Date: 2021-03