Zhu Zhaohua, Yu Qinghong, Leng Xiaomei, Xu Jianhua, Ren Limin, Wang Kun, Huang Cibo, Pan Yunfeng, Zhao Yi, Li Tianwang, Mei Yifang, Guan Meihua, Li Xiaoxia, Zhang Zhiyi, Wu Jing, Chen Yingjuan, Qu Yuan, Zhu Xiaotong, Liao Qiuju, Wang Zhe, Liao Zetao, Xi Yang, Deng Weiming, Wang Kang, Zhu Tingting, Zhang Yuping, Gao Lixia, Zhou Xiaoni, Han Weiyu, Ruan Guangfeng, Zhang Yan, Cao Peihua, Gao Peichun, Chen Haowei, Dang Qin, Cicuttini Flavia M, Hunter David J, Li Zhanguo, Zeng Xiaofeng, Ding Changhai
Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Sydney Musculoskeletal Health and Royal North Shore Hospital, Kolling Institute, University of Sydney, Sydney, Australia.
JAMA Intern Med. 2025 Jun 2. doi: 10.1001/jamainternmed.2025.1359.
IMPORTANCE: A recent study reported that methotrexate may reduce joint pain in patients with inflammatory hand osteoarthritis (OA). However, it remains unknown whether methotrexate has similar effects on inflammatory knee OA. OBJECTIVE: To examine whether methotrexate has symptom-relieving and disease-modifying effects for participants with knee OA and effusion-synovitis. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, placebo-controlled randomized clinical trial was conducted at 11 sites in China between July 18, 2019, and January 15, 2023. Community-dwelling patients with inflammatory knee OA with effusion-synovitis on magnetic resonance imaging were included. INTERVENTIONS: Participants were randomly assigned (1:1) to receive methotrexate, up to 15 mg weekly, or placebo using block randomization, stratified by study site. MAIN OUTCOMES AND MEASURES: The primary outcomes were knee visual analog scale (VAS) pain change and effusion-synovitis maximal area change, over 52 weeks in the intention-to-treat population. RESULTS: Of 278 participants screened, 215 participants (mean [SD] age, 60.4 [7.4] years; 191 [89%] female) were randomized (108 to the methotrexate group; 107 to the placebo group), and 175 (81%) completed the trial. Changes in VAS pain and effusion-synovitis maximal area were not significantly different between the methotrexate and placebo group over 52 weeks (between-group difference, 0.3 mm [95% CI, -6.7 to 7.3 mm] for VAS pain; 0.1 cm2 [95% CI, -0.8 to 1.0 cm2] for effusion-synovitis maximal area). No significant between-group differences were found for any of the prespecified secondary outcomes. At least 1 adverse event occurred in approximately 32 participants (29.6%) in the methotrexate group and 26 participants (24.3%) in the placebo group. CONCLUSIONS AND RELEVANCE: The results of this randomized clinical trial show that, compared to placebo, low-dose methotrexate did not reduce pain or effusion-synovitis over 52 weeks in patients with knee OA and effusion-synovitis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03815448.
重要性：最近一项研究报告称，甲氨蝶呤可能减轻炎症性手部骨关节炎（OA）患者的关节疼痛。然而，甲氨蝶呤对炎症性膝骨关节炎是否有类似作用仍不清楚。 目的：研究甲氨蝶呤对膝骨关节炎伴积液性滑膜炎参与者是否有症状缓解和疾病改善作用。 设计、地点和参与者：这项多中心、安慰剂对照随机临床试验于2019年7月18日至2023年1月15日在中国11个地点进行。纳入磁共振成像显示有积液性滑膜炎的社区居住炎症性膝骨关节炎患者。 干预措施：参与者通过区组随机化以1:1比例随机分配，接受每周最多15毫克的甲氨蝶呤或安慰剂，按研究地点分层。 主要结局和测量指标：主要结局是在意向性治疗人群中52周内膝关节视觉模拟量表（VAS）疼痛变化和积液性滑膜炎最大面积变化。 结果：在278名筛查参与者中，215名参与者（平均[标准差]年龄，60.4[7.4]岁；191名[89%]为女性）被随机分组（108名至甲氨蝶呤组；107名至安慰剂组），175名（81%）完成试验。在52周内，甲氨蝶呤组和安慰剂组之间VAS疼痛和积液性滑膜炎最大面积变化无显著差异（VAS疼痛组间差异为0.3毫米[95%CI，-6.7至7.3毫米]；积液性滑膜炎最大面积组间差异为0.1平方厘米[95%CI，-0.8至1.0平方厘米]）。在任何预先设定的次要结局中，组间均未发现显著差异。甲氨蝶呤组约32名参与者（29.6%）和安慰剂组26名参与者（24.3%）至少发生1次不良事件。 结论和相关性：这项随机临床试验结果表明，与安慰剂相比，低剂量甲氨蝶呤在52周内未减轻膝骨关节炎伴积液性滑膜炎患者的疼痛或积液性滑膜炎。 试验注册：ClinicalTrials.gov标识符：NCT03815448。
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