In a 52-week randomized trial low-dose methotrexate did not significantly reduce pain or inflammation in patients with inflammatory knee osteoarthritis.
Low-dose methotrexate did not significantly improve pain or reduce synovial inflammation compared with placebo in adults with inflammatory knee osteoarthritis, according to a randomized clinical trial conducted across 11 medical centers in China.
The 52-week study enrolled 215 community-dwelling adults with magnetic resonance imaging-confirmed knee osteoarthritis (OA) and effusion-synovitis. Participants were randomized 1:1 to receive either methotrexate (up to 15 mg weekly) or placebo. The mean age was 60.4 years, and 89% were women. A total of 175 participants (81%) completed the trial.
Primary outcomes were changes in visual analog scale (VAS)–measured knee pain and effusion-synovitis maximal area from baseline to 52 weeks. The mean change in VAS pain was −29.5 mm in the methotrexate group and −29.8 mm in the placebo group, for a between-group difference of 0.3 mm (95% CI, −6.7 to 7.3 mm). Effusion-synovitis area changed by −0.2 cm² with methotrexate and −0.3 cm² with placebo (difference, 0.1 cm²; 95% CI, −0.8 to 1.0 cm²).
Secondary outcomes, including WOMAC total and subscale scores, infrapatellar fat pad signal intensity, and OMERACT-OARSI response rates, showed no statistically significant or clinically meaningful differences. The response rate was 54.6% in the methotrexate group and 56.1% in the placebo group.
“Methotrexate, up to 15 mg weekly, compared with placebo, did not significantly improve VAS pain or effusion-synovitis size in participants with knee OA and effusion-synovitis,” said Dr. Changhai Ding, PhD, MD, of the Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China, and colleagues.
Methotrexate dosing began at 5 mg per week, increasing to 15 mg if tolerated. All participants received 5 mg folic acid weekly. Corticosteroids and trimethoprim were excluded due to interaction concerns.
At 52 weeks, the WOMAC total score decreased by −459.6 in the methotrexate group versus −441.5 in the placebo group (between-group difference, −18.2; 95% confidence interval, −148.4 to 112.0). SF-12, PHQ-9, general health status, and MRI-detected structural abnormalities such as cartilage defects and bone marrow lesions did not differ significantly between groups.
Adverse events occurred in 29.6% of the methotrexate group and 24.3% of the placebo group. Elevated liver enzymes (>1.5× upper limit of normal) were more frequent with methotrexate (19.4% vs 9.3%; P = .03). No serious adverse events were considered related to treatment.
A small subgroup with severe baseline knee pain (VAS ≥80 mm; n = 16) showed greater symptom improvement with methotrexate, but sample size was insufficient to draw definitive conclusions.
Researchers concluded that low-dose methotrexate did not produce clinically meaningful symptom relief or disease modification in patients with inflammatory knee OA over 1 year.
Full disclosures can be found in the published study.
Source: JAMA Internal Medicine