Kingsbury, S.R., Tharmanathan, P., Keding, A. et al. (21 more authors) (2024) Pain Reduction With Oral Methotrexate in Knee Osteoarthritis: A Randomized, Placebo-Controlled Clinical Trial. Annals of Internal Medicine, 177 (9). 1145 -1156. ISSN 0003-4819
Abstract
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: A total of 155 participants (64% women; mean age, 60.9 years; 50% Kellgren–Lawrence grade 3 to 4) were randomly assigned to methotrexate (n = 77) or placebo (n = 78). Follow-up was 86% (n = 134; methotrexate: 66, placebo: 68) at 6 months. Mean knee pain decreased from 6.4 (SD, 1.80) at baseline to 5.1 (SD, 2.32) at 6 months in the methotrexate group and from 6.8 (SD, 1.62) to 6.2 (SD, 2.30) in the placebo group. The primary intention-to-treat analysis showed a statistically significant pain reduction of 0.79 NRS points in favor of methotrexate (95% CI, 0.08 to 1.51; P = 0.030). There were also statistically significant treatment group differences in favor of methotrexate at 6 months for Western Ontario and McMaster Universities Osteoarthritis Index stiffness (0.60 points [CI, 0.01 to 1.18]; P = 0.045) and function (5.01 points [CI, 1.29 to 8.74]; P = 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 significant reduction in KOA pain, stiffness, and function at 6 months. Primary Funding Source: Versus Arthritis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Adverse events, Analgesics, Arthralgia, Hospital medicine, Inflammation, Knees, Methotrexate, Osteoarthritis, Pain, Rheumatology |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Musculoskeletal Medicine & Imaging (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 23 Jul 2024 09:56 |
Last Modified: | 30 Sep 2024 12:59 |
Status: | Published |
Publisher: | American College of Physicians |
Identification Number: | 10.7326/M24-0303 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:215072 |