Oral methotrexate effectively reduces pain and stiffness in knee osteoarthritis: Study

A new study published in the Annals of Internal Medicine showed that oral methotrexate in conjunction with regular analgesics greatly decreased knee osteoarthritis pain and stiffness and improved function when compared to a placebo.

Current therapies for osteoarthritis (OA) are very restricted. Painful synovitis is a common feature in osteoarthritis. The usual therapy for inflammatory arthritis is the disease-modifying anti-rheumatic medication methotrexate. For people with knee OA (KOA) symptoms, methotrexate (MTX) may be an option, according to a few small clinical and experimental investigations. The standard for treating synovitis in inflammatory arthritis is methotrexate which is a slow-acting anti-rheumatic medication. Therefore, Sarah Kingsbury and team conducted this study to find out how well MTX worked as an analgesic therapy for knee OA.

This multicenter, randomized, double-blind, placebo-controlled experiment investigated the effects of methotrexate on knee OA. Nearly, 207 persons with knee OA (mean age, 60.9 years) from 15 secondary care musculoskeletal clinics across the United Kingdom were randomly randomized to receive oral methotrexate once weekly, with a 6-week increase from 10 mg to 25 mg, or a matching placebo, while maintaining their regular analgesics. The participants who had radiographic abnormalities underwent knee discomfort on most days during the previous 3 months, and had a poor response to their current treatment were considered eligible. At 6 months, the main outcome measure was the average past-week knee pain, measured on a 0–10 scale. At a follow-up visit after a year, the study evaluated the longer-term response.

The key findings of this study were:

• A total of 155 subjects were randomly assigned to either methotrexate (77) or placebo (78). At 6 months, the follow-up rate was 86%.
• The mean knee pain decreased from 6.4 at baseline to 5.1 at 6 months in the methotrexate group, and from 6.8 to 6.2 in the placebo group.
• The primary intention-to-treat analysis revealed a statistically significant pain decrease of 0.79 NRS points in favor of methotrexate.
• At 6 months, Western Ontario and McMaster Universities Osteoarthritis Index stiffness and function showed statistically significant treatment group differences in favor of methotrexate.
• An examination of treatment adherence revealed a dose-response impact. Also, 4 unconnected significant adverse events (AEs) were recorded.

Overall, oral methotrexate added to standard therapy resulted in a statistically significant decrease in KOA pain, WOMAC stiffness and functioning, and a composite patient responder score. More research is needed to determine appropriate methotrexate dose, if benefits are greater in patients with elevated systemic inflammation levels, and cost effectiveness before bringing this medication to a potentially broad population.

Source:

Kingsbury, S. R., Tharmanathan, P., Keding, A., Watt, F. E., Scott, D. L., Roddy, E., Birrell, F., Arden, N. K., Bowes, M., Arundel, C., Watson, M., Ronaldson, S. J., Hewitt, C., Doherty, M., Moots, R. J., O’Neill, T. W., Green, M., Patel, G., Garrood, T., … Conaghan, P. G. (2024). Pain Reduction With Oral Methotrexate in Knee Osteoarthritis. In Annals of Internal Medicine (Vol. 177, Issue 9, pp. 1145–1156). American College of Physicians. https://doi.org/10.7326/m24-0303