类风湿关节炎患者在接受聚乙二醇化赛妥珠单抗治疗时，停用与继续使用伴随甲氨蝶呤的对比：一项随机对照试验的结果
Discontinuation vs. continuation of concomitant methotrexate in patients with rheumatoid arthritis on certolizumab pegol: results from a randomised, controlled trial.
作者信息
Asai Shuji, Kojima Toshihisa, Ishikawa Hajime, Miyake Nobumasa, Kodera Masanari, Hasegawa Hisanori, Sobue Yasumori, Kanayama Yasuhide, Shimada Hiromi, Hirano Yuji, Hidaka Toshihiko, Fujibayashi Takayoshi, Matsumoto Takuya, Kobayakawa Tomonori, Yasuoka Hidekata, Kato Takefumi, Hanabayashi Masahiro, Kaneko Yuko, Tada Masahiro, Murata Koichi, Misaki Kenta, Ando Masahiko, Kuwatsuka Yachiyo, Suzuki Mochihito, Terabe Kenya, Imagama Shiro
机构信息
Department of Orthopaedic Surgery and Rheumatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Aichi, Japan.
Department of Orthopaedic Surgery and Rheumatology, National Hospital Organisation, Nagoya Medical Centre, Nagoya, Japan.
出版信息
Arthritis Res Ther. 2025 Apr 5;27(1):82. doi: 10.1186/s13075-025-03548-1.
OBJECTIVE
The present non-inferiority study was designed to compare the effect of discontinuing versus continuing methotrexate (MTX) alongside certolizumab pegol (CZP) on maintaining low disease activity (LDA) in rheumatoid arthritis (RA) patients already stable on combination therapy.
METHODS
This multicentre, open-label, randomised, controlled trial included RA patients with sustained LDA (Clinical Disease Activity Index [CDAI] ≤ 10) for ≥ 12 weeks with CZP + MTX. Patients were randomised 1:1 by computer to either continue MTX (CZP + MTX group) or discontinue MTX after a 12-week reduction period (CZP group) using a dynamic allocation strategy with the minimisation method. The primary endpoint was the proportion of patients maintaining LDA without a flare (i.e., a CDAI score > 10 or intervention with rescue treatments for any reason) at week 36 (24 weeks after MTX discontinuation). Non-inferiority is verified if the lower limit of the 90% confidence interval (CI) using normal approximation for the difference in the proportion of cases that maintained LDA at week 36 between the intervention group and control group exceeds the non-inferiority margin.
RESULTS
All 84 screened patients were randomised to the CZP + MTX group (n = 41) and CZP group (n = 43), and were included in the efficacy analysis. Proportions (90% CI) of patients who maintained LDA at week 36 were 85.4% (76.3 to 94.4%) in the CZP + MTX group and 83.7% (74.5 to 93.0%) in the CZP group. The difference (90% CI) between the two groups was - 1.6% (-14.6 to 11.3%), with the lower limit of the 90% CI exceeding the non-inferiority margin of -18%. Reported adverse events were broadly similar between the two groups. The proportion of patients with gastrointestinal symptoms, as assessed by a self-administered questionnaire, was significantly lower in the CZP group than in the CZP + MTX group at week 36 (2.4% vs. 15.8%, P = 0.034).
CONCLUSION
Discontinuing concomitant MTX in RA patients on CZP is clinically feasible for maintaining LDA.
TRIAL REGISTRATION
Japan Registry of Clinical Trials (jRCTs041200048).
目的
本非劣效性研究旨在比较在已接受联合治疗且病情稳定的类风湿关节炎（RA）患者中，停用与继续使用甲氨蝶呤（MTX）联合赛妥珠单抗（CZP）对维持低疾病活动度（LDA）的效果。
方法
这项多中心、开放标签、随机对照试验纳入了使用CZP + MTX实现LDA持续≥12周（临床疾病活动指数[CDAI]≤10）的RA患者。采用最小化法的动态分配策略，通过计算机将患者按1:1随机分组，一组继续使用MTX（CZP + MTX组），另一组在为期12周的减量期后停用MTX（CZP组）。主要终点是在第36周（MTX停用后24周）维持LDA且无病情 flare（即CDAI评分>10或因任何原因接受挽救治疗干预）的患者比例。如果使用正态近似法计算的干预组与对照组在第36周维持LDA的病例比例差异的90%置信区间（CI）下限超过非劣效界值，则验证非劣效性。
结果
所有84例筛查患者均被随机分配至CZP + MTX组（n = 41）和CZP组（n = 43），并纳入疗效分析。CZP + MTX组在第36周维持LDA的患者比例（90%CI）为85.4%（76.3%至94.4%），CZP组为83.7%（74.5%至93.0%）。两组之间的差异（90%CI）为 -1.6%（-14.6%至11.3%），90%CI下限超过 -18%的非劣效界值。两组报告的不良事件大致相似。在第36周，通过自我管理问卷评估，CZP组胃肠道症状患者比例显著低于CZP + MTX组（2.4%对15.8%，P = 0.034）。
结论
在接受CZP治疗的RA患者中停用联合使用的MTX对维持LDA在临床上是可行的。
试验注册
日本临床试验注册中心（jRCTs041200048）
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