Department of Geriatric and Environmental Dermatology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
J Dermatol. 2023 Feb;50(2):183-194. doi: 10.1111/1346-8138.16609. Epub 2022 Oct 25.
Generalized pustular psoriasis is a potentially life-threatening neutrophilic skin disease characterized by recurrent flares of widespread erythema and eruption of sterile pustules. In the Effisayil™ 1 study (NCT03782792), 53 patients with a generalized pustular psoriasis flare were treated with placebo or spesolimab, a humanized anti-interleukin-36 receptor monoclonal antibody, the first targeted treatment to be studied in a randomized clinical trial. Spesolimab treatment resulted in rapid pustular and skin clearance, with an acceptable safety profile. Here, we evaluate the efficacy and safety of spesolimab in 29 Asian patients in the Effisayil™ 1 study. The primary endpoint, a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (no visible pustules) at Week 1, was achieved by 10 patients (62.5%) randomized to spesolimab and one patient (7.7%) randomized to placebo (risk difference 54.8, 95% confidence interval [CI] 17.3-79.8). The key secondary endpoint, a GPPGA total score of 0 or 1 (clear or almost clear skin) at Week 1, was achieved by eight (50.0%) and two (15.4%) patients, respectively (risk difference 34.6, 95% CI -3.1-64.7). This was similar to previously published data in the overall population in whom the primary and key secondary endpoints were achieved by 54% versus 6% and 43% versus 11% of patients, respectively. The percentages of Asian patients randomized to spesolimab with a GPPGA pustulation subscore of 0 and GPPGA total score of 0 or 1 were sustained above 60% for up to 12 weeks. In these patients, patient-reported outcomes also improved and markers of systemic inflammation were normalized. Eleven (68.8%) and eight (61.5%) of spesolimab- and placebo-treated patients, respectively, experienced at least one adverse event. In conclusion, spesolimab improved outcomes in Asian patients compared with placebo, supporting its use in the treatment of generalized pustular psoriasis flares.
泛发性脓疱型银屑病是一种潜在危及生命的中性粒细胞皮肤病，其特征为广泛红斑和无菌脓疱反复发作。在 Effisayil™1 研究（NCT03782792）中，53 例泛发性脓疱型银屑病发作患者接受安慰剂或 spesolimab（一种人源化抗白细胞介素-36 受体单克隆抗体）治疗，这是首次在随机临床试验中研究的靶向治疗药物。Spesolimab 治疗可迅速清除脓疱和皮肤，具有可接受的安全性。在此，我们评估了 spesolimab 在 Effisayil™1 研究的 29 例亚洲患者中的疗效和安全性。主要终点为第 1 周时全身性脓疱性银屑病医师整体评估（GPPGA）脓疱亚评分 0（无可见脓疱），接受 spesolimab 治疗的 10 例患者（62.5%）和接受安慰剂治疗的 1 例患者（7.7%）达到该终点（风险差异 54.8，95%置信区间 [CI] 17.3-79.8）。关键次要终点为第 1 周时 GPPGA 总评分 0 或 1（皮肤完全或几乎完全清除），分别有 8 例（50.0%）和 2 例（15.4%）患者达到该终点（风险差异 34.6，95%CI -3.1-64.7）。这与总体人群中先前发表的数据相似，主要和关键次要终点分别在 54%和 6%以及 43%和 11%的患者中达到。接受 spesolimab 治疗的亚洲患者中，GPPGA 脓疱亚评分和 GPPGA 总评分均为 0 或 1 的患者比例在 12 周内持续高于 60%。在这些患者中，患者报告的结局也得到改善，全身炎症标志物恢复正常。分别有 11 例（68.8%）和 8 例（61.5%）接受 spesolimab 和安慰剂治疗的患者发生至少 1 次不良事件。总之，与安慰剂相比，spesolimab 改善了亚洲患者的结局，支持其用于泛发性脓疱型银屑病发作的治疗。
