Tsai Tsen-Fang, Zheng Min, Ding Yangfeng, Song Zhiqi, Liu Quanzhong, Chen Ying, Hu Hanzhao, Xu Jinhua
Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan.
Department of Dermatology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Dermatol Ther (Heidelb). 2023 Dec;13(12):3097-3110. doi: 10.1007/s13555-023-01037-4. Epub 2023 Oct 16.
Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening skin disease. The global Effisayil 1 study investigated the efficacy and safety of spesolimab, a humanized monoclonal antibody targeting the IL-36 receptor, in patients experiencing GPP flare. This analysis aimed to explore the efficacy and safety of spesolimab in the Chinese subgroup of Effisayil 1.
Effisayil 1 was a multicenter, randomized, double-blind, placebo-controlled phase II study. Eligible patients with a GPP flare were randomly assigned (2:1) to receive a single intravenous dose of spesolimab (900 mg) or placebo on day 1. On day 8, patients who had persistent symptoms that met a predefined criterion could receive open-label spesolimab. After day 8, patients with recurrent flares following clinical response could receive rescue treatment with open-label spesolimab. The primary end point was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation sub-score of 0 at week 1. The key secondary end point was a GPPGA total score of 0 or 1 at week 1.
Eleven Chinese patients were randomized, with five patients receiving spesolimab and six receiving placebo. At week 1, 60.0% (3/5) of patients in the spesolimab group and 16.7% (1/6) of patients in the placebo group achieved a GPPGA pustulation sub-score of 0 (risk difference 43.3%; 95% CI -22.6, 86.2); 60.0% and 16.7% of patients in the spesolimab and placebo group, respectively, achieved a GPPGA total score 0 or 1 (risk difference 43.3%; 95% CI -22.6, 86.2). Overall, four patients in each group of the spesolimab and the placebo groups reported at least one adverse event (AE) by week 1, with two and three reporting drug-related AEs, respectively. One patient reported a serious AE that was not considered to be drug related. No death occurred during the study period.
In the Chinese subgroup of the Effisayil 1 study, more patients receiving spesolimab experienced lesion clearance than those on placebo at week 1, with an acceptable safety profile that was consistent with the global study population.
NCT03782792.
泛发性脓疱型银屑病（GPP）是一种罕见且可能危及生命的皮肤病。全球Effisayil 1研究调查了靶向白细胞介素-36受体的人源化单克隆抗体司库奇尤单抗在GPP发作患者中的疗效和安全性。本分析旨在探讨司库奇尤单抗在Effisayil 1研究中国亚组中的疗效和安全性。
Effisayil 1是一项多中心、随机、双盲、安慰剂对照的II期研究。符合条件的GPP发作患者在第1天被随机分配（2:1）接受单次静脉注射司库奇尤单抗（900 mg）或安慰剂。在第8天，有持续症状且符合预定义标准的患者可接受开放标签的司库奇尤单抗治疗。第8天后，临床缓解后复发的患者可接受开放标签的司库奇尤单抗抢救治疗。主要终点是第1周时泛发性脓疱型银屑病医师整体评估（GPPGA）脓疱分项评分达到0分。关键次要终点是第1周时GPPGA总分达到0或1分。
11名中国患者被随机分组，5名患者接受司库奇尤单抗治疗，6名患者接受安慰剂治疗。在第1周时，司库奇尤单抗组60.0%（3/5）的患者和安慰剂组16.7%（1/6）的患者GPPGA脓疱分项评分达到0分（风险差异43.3%；95%CI -22.6，86.2）；司库奇尤单抗组和安慰剂组分别有60.0%和16.7%的患者GPPGA总分达到0或1分（风险差异43.3%；95%CI -22.6，86.2）。总体而言，司库奇尤单抗组和安慰剂组每组各有4名患者在第1周时报告了至少1次不良事件（AE），分别有2名和3名患者报告了与药物相关的AE。1名患者报告了1次严重AE，但不认为与药物相关。研究期间未发生死亡。
在Effisayil 1研究的中国亚组中，第1周时接受司库奇尤单抗治疗的患者比接受安慰剂治疗的患者更多地实现了皮损清除，其安全性可接受，与全球研究人群一致。
NCT03782792。
