非布司他与依托考昔治疗痛风发作的疗效和安全性比较：一项2期、多中心、开放标签、活性药物对照、随机非劣效性试验

Efficacy and Safety of Firsekibart Compared to Etoricoxib for Gout Flares: A Phase 2, Multicenter, Open-label, Active-controlled, Randomized Non-inferiority Trial.

作者信息

Kong Ning, Xue Yu, Mao Li, Qian Long, Guo Hongtao, Hu Jiankang, Yuan Fenghong, Li Rongbin, Duan Xinwang, Yu Jing, Gou Wei, Yang Lei, Wei Hua, Li Rongping, Xu Qian, Luo Tianhong, Zhang Xu, Zou Hejian

机构信息

Department of Rheumatology and Immunology, Huashan Hospital, Fudan University, Shanghai, China.

Huai'an First People's Hospital, Huai'an, China.

出版信息

Rheumatol Ther. 2025 Aug 20. doi: 10.1007/s40744-025-00790-6.

DOI:10.1007/s40744-025-00790-6

PMID:40833487

Abstract

INTRODUCTION

Firsekibart, an anti-interleukin (IL)-1β monoclonal antibody, has demonstrated more sustained control of gout flares compared with compound betamethasone in previous clinical studies. This study evaluated the efficacy and safety of firsekibart versus etoricoxib for the treatment of frequent gout flares.

METHODS

In this phase 2, randomized, open-label, active-controlled, multicenter study (NCT05936268), adults with gout according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) 2015 criteria experiencing frequent flares (≥ 2 flares within 12 months pre-screening) were randomized (1:1) to receive either a single subcutaneous injection of firsekibart 200 mg, or once-daily oral etoricoxib 120 mg administered until pain remission or treatment intolerance for up to 8 days. The primary endpoint was change from baseline in target joint pain intensity (0-100 mm visual analogue scale [VAS]) 72 h post-treatment. Non-inferiority (margin: 10 mm) was assessed first; if achieved, superiority was subsequently evaluated. Safety was also evaluated.

RESULTS

Overall, 123 patients received firsekibart (n = 61) or etoricoxib (n = 62). Firsekibart was non-inferior and superior to etoricoxib in change from baseline in target joint pain VAS scores at 72 h post-treatment (difference: - 10.91 mm; 95% confidence interval [CI]: - 18.11, - 3.72). Treatment-emergent adverse events (TEAEs) occurred in 77.0% (n = 47) and 51.6% (n = 32) of patients receiving firsekibart and etoricoxib, respectively. The most common TEAE in both groups was hypertriglyceridemia. No TEAEs led to treatment discontinuation or study withdrawal, and no treatment-related serious adverse events (AEs) or deaths were reported.

CONCLUSIONS

Compared with etoricoxib, firsekibart provides superior target joint pain relief and is well-tolerated in patients with frequent gout flares.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT05936268; date of registration: 7 July 2023.

摘要

引言

Firsekibart是一种抗白细胞介素（IL）-1β单克隆抗体，在先前的临床研究中，与复方倍他米松相比，它对痛风发作的控制更持久。本研究评估了Firsekibart与依托考昔治疗频繁痛风发作的疗效和安全性。

方法

在这项2期、随机、开放标签、活性对照、多中心研究（NCT05936268）中，根据美国风湿病学会（ACR）和欧洲抗风湿病联盟（EULAR）2015年标准诊断为痛风且发作频繁（筛查前12个月内≥2次发作）的成年人被随机（1:1）分配，接受单次皮下注射200mg的Firsekibart，或每日一次口服120mg依托考昔，持续给药直至疼痛缓解或出现治疗不耐受，最长8天。主要终点是治疗72小时后目标关节疼痛强度相对于基线的变化（0-100mm视觉模拟量表[VAS]）。首先评估非劣效性（界值：10mm）；如果达到非劣效性，则随后评估优效性。同时也评估了安全性。

结果

总体而言，123例患者接受了Firsekibart（n = 61）或依托考昔（n = 62）治疗。在治疗72小时后，Firsekibart在目标关节疼痛VAS评分相对于基线的变化方面不劣于且优于依托考昔（差异：-10.91mm；95%置信区间[CI]：-18.11，-3.72）。接受Firsekibart和依托考昔治疗的患者中，分别有77.0%（n = 47）和51.6%（n = 32）发生了治疗中出现的不良事件（TEAE）。两组中最常见的TEAE都是高甘油三酯血症。没有TEAE导致治疗中断或研究退出，也没有报告与治疗相关的严重不良事件（AE）或死亡。