比较两种甲氨蝶呤递增剂量策略在活动性类风湿关节炎中的疗效：一项多中心、平行组、随机对照试验。

Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial.

机构信息

Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India

出版信息

Ann Rheum Dis. 2021 Nov;80(11):1376-1384. doi: 10.1136/annrheumdis-2021-220512. Epub 2021 Jun 10.

DOI:10.1136/annrheumdis-2021-220512

PMID:34112656

Abstract

OBJECTIVES

There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX.

METHODS

This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat.

RESULTS

178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen.

CONCLUSION

A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially.

TRIAL REGISTRATION NUMBER

CTRI/2018/12/016549.

摘要

目的

目前尚无比较甲氨蝶呤（MTX）不同剂量递增策略的头对头试验。我们比较了“常规”（每 4 周 5 毫克）与“快速”（每 2 周 5 毫克）递增口服 MTX 的疗效、安全性和耐受性。

方法

这是一项多中心、开放标签（评估者设盲）RCT，纳入了年龄在 18-55 岁之间、疾病持续时间<5 年且未接受 DMARDs 治疗的活动性 RA 患者。患者以 1:1 的比例随机分为常规或快速递增组，两组均以 15mg/周起始 MTX 治疗，最大剂量为 25mg/周。主要结局为 16 周时 EULAR 良好反应，次要结局为ΔDAS28 和不良事件（AE）。分析为意向治疗。

结果

178 例平均 DAS28-CRP 为 5.4(1.1)的患者被随机分为常规（n=89）或快速递增组（n=89）。16 周时，常规组（28.1%）和快速递增组（22.5%）的 EULAR 良好反应率无差异（p=0.8）。8 周时（-0.9，-0.8，p=0.72）和 16 周时（-1.3，-1.3，p=0.98）的平均ΔDAS28-CRP 也无差异。甚至在 24 周（扩展随访）时，反应也相似。8 周和 16 周时，两组间ΔHAQ 或 MTX-多聚谷氨酸 1-3 水平均无差异。8 周时，快速递增组的胃肠道 AE 更高（27%，40%，p=0.048），但 16 周时无差异。两组间的血细胞减少症、转氨基酶升高或药物停药/剂量减少无差异。两组均无严重 AE 发生。