探索 spesolimab 对中重度化脓性汗腺炎患者影响的概念验证研究：一项随机双盲安慰剂对照临床试验。

Proof-of-concept study exploring the effect of spesolimab in patients with moderate-to-severe hidradenitis suppurativa: a randomized double-blind placebo-controlled clinical trial.

机构信息

Department of Dermatology, Mayo Clinic, Rochester, MN, USA.

Department of Dermatology, Erasmus University Medical Center, Rotterdam, the Netherlands.

出版信息

Br J Dermatol. 2024 Sep 18;191(4):508-518. doi: 10.1093/bjd/ljae144.

DOI:10.1093/bjd/ljae144

PMID:38576350

Abstract

BACKGROUND

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies.

OBJECTIVES

To explore the effects of spesolimab treatment in patients with HS.

METHODS

This randomized double-blind placebo-controlled proof-of-clinical-concept (PoCC) study was conducted at 25 centres across 12 countries from 3 May 2021 to 21 April 2022. Patients had moderate-to-severe HS for ≥ 1 year before enrolment. Patients were randomized (2 : 1) to receive a loading dose of 3600-mg intravenous spesolimab (1200 mg at weeks 0, 1 and 2) or matching placebo, followed by maintenance with either 1200-mg subcutaneous spesolimab every 2 weeks from weeks 4 to 10 or matching placebo. The primary endpoint was the percentage change from baseline in total abscess and inflammatory nodule (AN) count at week 12. Secondary endpoints were the absolute change from baseline in the International Hidradenitis Suppurativa Severity Score System (IHS4), percentage change from baseline in draining tunnel (dT) count, the proportion of patients achieving a dT count of 0, absolute change from baseline in the revised Hidradenitis Suppurativa Area and Severity Index (HASI-R), the proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR50), the proportion of patients with ≥ 1 flare (all at week 12) and patient-reported outcomes.

RESULTS

In this completed trial, randomized patients (n = 52) received spesolimab (n = 35) or placebo (n = 17). The difference vs. placebo in least squares mean is reported. At week 12, the percentage change in total AN count was similar between treatment arms: -4.1% [95% confidence interval (CI) -31.7 to 23.4]. There was greater numerical improvement in the spesolimab arm, as measured by IHS4 (13.9, 95% CI -25.6 to -2.3); percentage change from baseline in dT count (-96.6%, 95% CI -154.5 to -38.8); and the proportion of patients achieving a dT count of 0 (18.3%, 95% CI -7.9 to 37.5). Spesolimab treatment also improved HASI-R and HiSCR50 vs. placebo. Spesolimab demonstrated a favourable safety profile, similar to that observed in trials in other diseases.

CONCLUSIONS

This exploratory PoCC study supports the development of spesolimab as a new therapeutic option in HS.

摘要

背景

化脓性汗腺炎（HS）是一种慢性炎症性皮肤病，疾病负担相当大。现有的治疗选择有限，且往往不尽人意；对于有效的靶向治疗存在着高度未满足的需求。

目的

探讨 spesolimab 治疗 HS 患者的效果。

方法

这是一项在 2021 年 5 月 3 日至 2022 年 4 月 21 日期间，在 12 个国家的 25 个中心进行的随机、双盲、安慰剂对照概念验证（PoCC）研究。患者在入组前有 1 年以上的中重度 HS 病史。患者按 2:1 的比例随机（2:1）接受 3600mg 静脉注射 spesolimab（第 0、1 和 2 周各 1200mg）或匹配的安慰剂，随后分别接受 1200mg 每 2 周皮下注射 spesolimab 或匹配的安慰剂，持续 10 周（第 4 至 10 周）。主要终点是治疗 12 周时总脓肿和炎症性结节（AN）计数与基线相比的变化百分比。次要终点是国际化脓性汗腺炎严重程度评分系统（IHS4）基线绝对变化、引流隧道（dT）计数与基线相比的变化百分比、dT 计数为 0 的患者比例、改良化脓性汗腺炎面积和严重程度指数（HASI-R）的基线绝对变化、化脓性汗腺炎临床应答（HiSCR50）的患者比例、治疗 12 周时（均）≥ 1 次发作的患者比例以及患者报告的结局。

结果

在这项完成的试验中，随机分组的患者（n=52）接受 spesolimab（n=35）或安慰剂（n=17）治疗。报告了与安慰剂相比的最小二乘均数差异。治疗 12 周时，两种治疗组的总 AN 计数变化百分比相似：-4.1%（95%置信区间[CI] -31.7 至 23.4）。与安慰剂相比，spesolimab 组的数值改善更大，表现为 IHS4 改善（13.9，95%CI -25.6 至 -2.3）、dT 计数下降（-96.6%，95%CI -154.5 至 -38.8）和达到 dT 计数为 0 的患者比例（18.3%，95%CI -7.9 至 37.5）。与安慰剂相比，spesolimab 治疗还改善了 HASI-R 和 HiSCR50。与其他疾病的试验中观察到的情况类似，spesolimab 显示出良好的安全性。