Adding oral methotrexate to care reduces pain in knee osteoarthritis, suggests study

A randomized, placebo-controlled trial found that oral methotrexate added to usual analgesia care showed statistically significant reduction in knee osteoarthritis pain at 6 months, with improvements also noted in some secondary outcomes. This is important because knee osteoarthritis is associated with significant pain and disability, and treatments are limited. The findings are published in Annals of Internal Medicine.

Researchers from the University of Leeds randomly assigned 155 participants with symptomatic knee osteoarthritis to either oral methotrexate once weekly or matched placebo with continued usual analgesia over 12 months to assess symptomatic benefits of methotrexate. The participants had knee osteoarthritis diagnosed by radiography and knee pain (severity ≥4 out of 10) on most days in the past 3 months with inadequate response to current medication. The participants were assessed for knee pain at 6 months, with 12-month follow-up to assess longer term response. Secondarily, they were assessed for knee stiffness and function outcomes and adverse events.

The researchers found that methotrexate added to usual analgesia showed statistically significant reduction in pain, with improvements in some secondary outcomes. The two treatment groups had similar outcomes by 12 months, although loss to follow-up was higher and mean methotrexate dose lower by 12 months in the methotrexate group. According to the authors, further work is required to understand adequate methotrexate dosing, whether benefits are greater in those with elevated systemic inflammation levels, and to consider cost-effectiveness before introducing this therapy for a potentially large population.

Reference:

 Sarah R. Kingsbury, Puvan Tharmanathan, Ada Keding, Fiona E. Watt,  David L. Scott, PhD, Edward Roddy, Fraser Birrell, Pain Reduction With Oral Methotrexate in Knee Osteoarthritis: A Randomized, Placebo-Controlled Clinical Trial, Annals of Internal Medicine, https://doi.org/10.7326/M24-0303.