K Yamasaki1, H Nakagawa2, Y Kubo3, K Ootaki4. 1. Department of Dermatology, Tohoku University Graduate School of Medicine, Tohoku University Hospital, 1-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi, 980-8574, Japan. 2. Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan. 3. Department of Dermatology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. 4. Kyowa Hakko Kirin Co. Ltd, Tokyo, Japan.
Abstract
BACKGROUND: A T-helper (Th) cell subset Th17 preferentially produces interleukin (IL)-17 and plays a pivotal role in the pathogenesis of psoriasis. However, the pathological roles of IL-17 cascades in generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE) have not been well established. OBJECTIVES: To evaluate the efficacy and safety of brodalumab, a human immunoglobulin G2 monoclonal antibody against human IL-17-receptor A (IL-17RA), in Japanese patients with GPP and PsE. METHODS: This was an open-label, multicentre, long-term phase III study in Japanese patients with rare and severe types of psoriasis. Patients received brodalumab 140 mg at day 1 and weeks 1 and 2, and then every 2 weeks until week 52. The primary endpoint was the Clinical Global Impression of Improvement (CGI). Safety evaluations included treatment-emergent adverse events (AEs) and changes in laboratory parameters. RESULTS: A total of 12 patients with GPP and 18 with PsE were enrolled. Ten patients with GPP and 16 with PsE completed the study. At week 52 (last observation carried forward), CGI remission or improvement was achieved in 11 patients with GPP and 18 with PsE. The most commonly reported AE was nasopharyngitis (33·3%). Five serious AEs occurred during the study. However, none was considered treatment-related. CONCLUSIONS: Brodalumab significantly improved the symptoms of patients with GPP and PsE throughout the 52 weeks, and demonstrated favourable safety profiles without any new safety signals. Inhibition of IL-17RA-mediated signalling by brodalumab is expected to be a promising new treatment option for patients with GPP and PsE.
BACKGROUND: A T-helper (Th) cell subset Th17 preferentially produces interleukin (IL)-17 and plays a pivotal role in the pathogenesis of psoriasis. However, the pathological roles of IL-17 cascades in generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE) have not been well established. OBJECTIVES: To evaluate the efficacy and safety of brodalumab, a human immunoglobulin G2 monoclonal antibody against humanIL-17-receptor A (IL-17RA), in Japanese patients with GPP and PsE. METHODS: This was an open-label, multicentre, long-term phase III study in Japanese patients with rare and severe types of psoriasis. Patients received brodalumab 140 mg at day 1 and weeks 1 and 2, and then every 2 weeks until week 52. The primary endpoint was the Clinical Global Impression of Improvement (CGI). Safety evaluations included treatment-emergent adverse events (AEs) and changes in laboratory parameters. RESULTS: A total of 12 patients with GPP and 18 with PsE were enrolled. Ten patients with GPP and 16 with PsE completed the study. At week 52 (last observation carried forward), CGI remission or improvement was achieved in 11 patients with GPP and 18 with PsE. The most commonly reported AE was nasopharyngitis (33·3%). Five serious AEs occurred during the study. However, none was considered treatment-related. CONCLUSIONS:Brodalumab significantly improved the symptoms of patients with GPP and PsE throughout the 52 weeks, and demonstrated favourable safety profiles without any new safety signals. Inhibition of IL-17RA-mediated signalling by brodalumab is expected to be a promising new treatment option for patients with GPP and PsE.
Authors: Andrew Johnston; Xianying Xing; Liza Wolterink; Drew H Barnes; ZhiQiang Yin; Laura Reingold; J Michelle Kahlenberg; Paul W Harms; Johann E Gudjonsson Journal: J Allergy Clin Immunol Date: 2016-12-31 Impact factor: 10.793
Authors: Mika Yamanaka-Takaichi; Soha Ghanian; David A Katzka; Rochelle R Torgerson; Afsaneh Alavi Journal: Am J Clin Dermatol Date: 2022-04-15 Impact factor: 6.233