Oral Methotrexate Reduces Knee Osteoarthritis Pain and Stiffness Significantly in 6-Month Study

UK: A randomized, double-blind trial demonstrates that oral methotrexate, when combined with standard treatments, showed a statistically significant reduction in knee osteoarthritis (KOA) pain, stiffness, and functional impairment at the 6-month mark. The findings were published online in the Annals of Internal Medicine on 30 July 2024.

Osteoarthritis is classified as a degenerative disease that causes subchondral sclerosis, subchondral cysts, bone remodeling (osteophyte production), and loss of articular cartilage. The illness is typified by joint discomfort, functional disability, and a marked decline in life quality. Conservative (non-operative) and surgical (operative) approaches are typically used in KOA management. Pain, stiffness, restricted joint mobility, and muscle weakness are common KOA symptoms that severely hinder day-to-day activities and job performance. Considering this, Sarah R. Kingsbury, from Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre, Leeds, United Kingdom, et.al conducted a study to assess the symptomatic benefits of methotrexate in Knee Osteoarthritis.

For this purpose, the research team conducted a randomized, multicenter, double-blind, placebo-controlled trial involving 207 participants from the United Kingdom. The trial was conducted from 13 June 2014 to 13 October 2017 in the 15 secondary care musculoskeletal clinics in the United Kingdom.

The study included 207 individuals who had radiographic KOA and knee pain (severity ≥4 out of 10) on most days during the previous three months and were not responding well to their existing treatment were contacted. Over 12 months, they were randomized 1:1 to receive oral methotrexate once weekly (6-week escalation: 10 to 25 mg) or a matched placebo, while continuing with their regular analgesic regimen. Average knee pain (numerical rating scale [NRS] 0 to 10) at six months was the main outcome, and a 12-month follow-up was conducted to evaluate the longer-term response. Adverse events (AEs) and outcomes related to knee stiffness and function were included as secondary end goals.

The findings revealed that:

• 64% of women with Kellgren-Lawrence grades 3 to 4 received methotrexate at random. At six months, 86% of respondents were still following up.
• In the methotrexate group, mean knee pain dropped from 6.4 at baseline to 5.1 at 6 months, while in the placebo group, it reduced from 6.8 to 6.2.
• A statistically significant pain decrease of 0.79 NRS points in favor of methotrexate was observed in the primary intention-to-treat analysis.
• At six months, the McMaster University Osteoarthritis Index stiffness and function for Western Ontario and methotrexate showed statistically significant differences across treatment groups.
• A dose-response impact was substantiated by a study of treatment adherence. Four separate major adverse events were noted.

“Throughout six months, the addition of oral methotrexate to standard therapies considerably decreased pain, stiffness, and functional impairment in patients with osteoarthritis of the knee. Hence methotrexate is proven safe to use for the treatment of osteoarthritis of the knee”, researchers concluded.

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. https://doi.org/10.7326/M24-0303