RCT: Methotrexate Shows Modest Pain Reduction in Knee Osteoarthritis, More Research Needed – Ann Intern Med

Study Design and Population: This multicenter, randomized, double-blind, placebo-controlled trial evaluated the effects of oral methotrexate on 207 participants with symptomatic knee osteoarthritis (KOA) who had persistent knee pain despite prior treatments. Conducted across 15 musculoskeletal clinics in the UK from June 2014 to October 2017, participants were randomly assigned to receive either methotrexate or placebo over a 12-month period.

Main Findings: At 6 months, methotrexate resulted in a modest reduction in knee pain, with a statistically significant difference of 0.79 points on the NRS compared to placebo (95% CI, 0.08 to 1.51; P = 0.030). Small but statistically significant improvements were also noted in knee stiffness and function. However, the clinical significance of these findings remains uncertain, and potential side effects of methotrexate warrant caution.

Implications for Practice: While methotrexate may offer some symptomatic relief for patients with knee osteoarthritis who do not respond to standard treatments, the modest reduction in pain and improvement in function observed in this study may not justify its routine use given the potential for significant side effects. The small magnitude of benefit suggests that methotrexate should be considered cautiously and only in select patients. Further research is necessary to confirm these findings and to better understand the risk-benefit profile of methotrexate in this population before broader clinical adoption.

Reference: Kingsbury, S. R., Tharmanathan, P., Keding, A., Watt, F. E., Scott, D. L., Roddy, E., Birrell, F., & Conaghan, P. G. (2024). Pain Reduction With Oral Methotrexate in Knee Osteoarthritis: A Randomized, Placebo-Controlled Clinical Trial. Annals of Internal Medicine. DOI: 10.7326/M24-0303.