澳大利亚莫纳什大学Flavia M Cicuttini团队研究了甲氨蝶呤治疗伴有滑膜炎的手骨关节炎的疗效。2023年10月12日，《柳叶刀》杂志发表了这一成果。

手部骨关节炎是一种致残性疾病，缺乏有效的治疗方法。手骨关节炎伴滑膜炎是一种常见的与疼痛相关的炎症表型。该研究旨在检查甲氨蝶呤对手骨关节炎和滑膜炎患者治疗6个月时的疗效和安全性。

在这项多地点、平行组、双盲、随机、安慰剂对照试验中，研究组从澳大利亚墨尔本、霍伯特、阿德莱德和珀斯的社区招募患有手骨关节炎（至少一个关节Kellgren和Lawrence分级≥2级）和MRI检测的1级或以上滑膜炎的参与者（年龄40-75岁）。

将参与者随机分组（1:1），根据研究地点和自我报告的性别分层，分别接受甲氨蝶呤20 mg或相同的安慰剂，每周口服一次，持续6个月。主要结局是疼痛减轻（用100毫米视觉模拟量表测量；VAS），在6个月时对意向治疗人群进行评估。对所有随机分配的参与者的安全结局进行评估。

2017年11月22日至2021年11月8日，202名参与者被评估为合格，其中97名（48%）被随机分配接受甲氨蝶呤（n=50）或安慰剂（n=47）。97名参与者中，女性68人（70%），男性29人（30%）。甲氨蝶呤组50名参与者中有42名（84%）提供了主要结局数据，安慰剂组47名参与者中有40名（85%）。6个月时，甲氨蝶呤组VAS疼痛的平均变化为-15.2 mm，安慰剂组为-7.7 mm，组间平均差异为-9.9 mm，效应量（标准化平均差）为0.45。甲氨蝶呤组50名参与者中有31名（62%）发生不良事件，安慰剂组47名参与者中有28名（60%）。

研究结果表明，用20 mg甲氨蝶呤治疗手骨关节炎和滑膜炎患者6个月，对减轻疼痛有中等但有潜在临床意义的效果，这证明了甲氨蝶呤可能在炎症型手骨关节炎的治疗中起作用。

附：英文原文

Title: Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial

Author: Yuanyuan Wang, Graeme Jones, Helen I Keen, Catherine L Hill, Anita E Wluka, Jessica Kasza, Andrew J Teichtahl, Benny Antony, Richard OSullivan, Flavia M Cicuttini

Issue&Volume: 2023-10-12

Abstract:

Background

Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis.

Methods

In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged 40–75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and MRI-detected synovitis of grade 1 or more were recruited from the community in Melbourne, Hobart, Adelaide, and Perth, Australia. Participants were randomly assigned (1:1) using block randomisation, stratified by study site and self-reported sex, to receive methotrexate 20 mg or identical placebo orally once weekly for 6 months. The primary outcome was pain reduction (measured with a 100 mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were assessed in all randomly assigned participants. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000877381).

Findings

Between Nov 22, 2017, and Nov 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were female and 29 (30%) were male. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was –15·2 mm (SD 24·0) in the methotrexate group and –7·7 mm (25·3) in the placebo group, with a mean between-group difference of –9·9 (95% CI –19·3 to –0·6; p=0·037) and an effect size (standardised mean difference) of 0·45 (0·03 to 0·87). Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group.

Interpretation

Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype.

DOI: 10.1016/S0140-6736(23)01572-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01572-6/abstract