Pain Reduction With Oral Methotrexate in Knee Osteoarthritis

作者：Sarah R. Kingsbury, Puvan Tharmanathan, Ada Keding, Fiona E. Watt, David Lloyd Scott, Edward Roddy, Fraser N Birrell, Nigel Arden, M.A. Bowes, Catherine E. Arundel, Michelle Watson, Sarah Jane Ronaldson, Catherine Hewitt, Michael Doherty, Robert J. Moots, Terence W O’Neill, Michael Green, Gulam Patel, Toby Garrood, Christopher John Edwards, Phil J. Walmsley, Tom Sheeran, David John Torgerson, Philip G. Conaghan · 发表于：Annals of Internal Medicine · 年份：2024 · DOI：10.7326/m24-0303 · 被引用次数：40 · 研究领域：Osteoarthritis Treatment and Mechanisms、Rheumatoid Arthritis Research and Therapies、Spondyloarthritis Studies and Treatments

BACKGROUND: Treatments for osteoarthritis (OA) are limited. Previous small studies suggest that the antirheumatic drug methotrexate may be a potential treatment for OA pain. OBJECTIVE: To assess symptomatic benefits of methotrexate in knee OA (KOA). DESIGN: A multicenter, randomized, double-blind, placebo-controlled trial done between 13 June 2014 and 13 October 2017. (ISRCTN77854383; EudraCT: 2013-001689-41). SETTING: 15 secondary care musculoskeletal clinics in the United Kingdom. PARTICIPANTS: A total of 207 participants with symptomatic, radiographic KOA and knee pain (severity ≥4 out of 10) on most days in the past 3 months with inadequate response to current medication were approached for inclusion. INTERVENTION: Participants were randomly assigned 1:1 to oral methotrexate once weekly (6-week escalation 10 to 25 mg) or matched placebo over 12 months and continued usual analgesia. MEASUREMENTS: The primary end point was average knee pain (numerical rating scale [NRS] 0 to 10) at 6 months, with 12-month follow-up to assess longer-term response. Secondary end points included knee stiffness and function outcomes and adverse events (AEs). RESULTS: = 0.008). Treatment adherence analysis supported a dose-response effect. Four unrelated serious AEs were reported (methotrexate: 2, placebo: 2). LIMITATION: Not permitting oral methotrexate to be changed to subcutaneous delivery for intolerance. CONCLUSION: Oral methotrexate added to usual medications demonstrated statistically sig...