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. 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). 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. 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. National Health and Medical Research Council of Australia.

中文翻译：

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甲氨蝶呤治疗手部骨关节炎伴滑膜炎（方法）：一项澳大利亚、多中心、平行组、双盲、随机、安慰剂对照试验

手部骨关节炎是一种致残性疾病，几乎没有有效的治疗方法。手部骨关节炎伴滑膜炎是一种与疼痛相关的常见炎症表型。我们的目的是检查 6 个月时甲氨蝶呤对手部骨关节炎和滑膜炎参与者的疗效和安全性。在这项多中心、平行组、双盲、随机、安慰剂对照试验中，参与者（年龄 40-75 岁）患有手部骨关节炎（至少一个关节的 Kellgren 和 Lawrence 分级≥2 级）且 MRI 检测到 2 级滑膜炎从澳大利亚墨尔本、霍巴特、阿德莱德和珀斯的社区招募了 1 名或多名。参与者被随机分配（1:1），按研究地点和自我报告的性别分层，每周一次口服甲氨蝶呤 20 mg 或相同的安慰剂，持续 6 个月。主要结局是在意向治疗人群中评估的 6 个月时研究组的疼痛减轻（用 100 毫米视觉模拟量表测量；VAS）。对所有随机分配的参与者进行安全结果评估。该试验已在澳大利亚新西兰临床试验注册中心注册（ACTRN12617000877381）。2017 年 11 月 22 日至 2021 年 11 月 8 日期间，在接受资格评估的 202 名参与者中，97 名 (48%) 被随机分配接受甲氨蝶呤 (n=50) 或安慰剂 (n=47)。97 名参与者中有 68 名（70%）为女性，29 名（30%）为男性。甲氨蝶呤组 50 名参与者中的 42 名 (84%) 和安慰剂组 47 名参与者中的 40 名 (85%) 提供了主要结局数据。6 个月时，甲氨蝶呤组 VAS 疼痛的平均变化为 –15·2 mm (SD 24·0)，安慰剂组为 –7·7 mm (25·3)，组间平均差异为 – 9·9（95% CI –19·3 至 –0·6；p=0·037），效应大小（标准化平均差）为 0·45（0·03 至 0·87）。甲氨蝶呤组 50 名参与者中有 31 名 (62%) 发生了不良事件，安慰剂组 47 名参与者中有 28 名 (60%) 发生了不良事件。用 20 mg 甲氨蝶呤治疗手部骨关节炎和滑膜炎 6 个月，对减轻疼痛具有中等但具有潜在临床意义的效果，这提供了甲氨蝶呤可能在治疗具有炎症表型的手部骨关节炎中发挥作用的概念证据。澳大利亚国家健康和医学研究委员会。