Methotrexate Eases Pain, Synovitis in Knee OA

April 11, 2014

In a small placebo-controlled trial, methotrexate significantly improved pain and other symptoms of knee osteoarthritis and predictably modest adverse effects.

Abou-Raya A, Abou-Raya S, Khadrawe T. Methotrexate in the treatment of symptomatic knee osteoarthritis: randomised placebo-controlled trial.Ann Rheum Dis (2014) Mar 27. doi: 10.1136/annrheumdis-2013-204856. [Epub ahead of print]  

A team of doctors in Egypt has decided to test methotrexate (MTX), which is widely used in rheumatoid arthritis and other inflammatory diseases, for its effects on inflammation-related pain and synovitis in knee osteoarthritis (OA).

In a 28-week double-blind, randomized controlled trial of 144 patients with knee OA conducted at Alexandria University in Egypt, MTX was found to reduce pain and inflammation as well as improve physical function.

Participants, most of whom were overweight women (mean body mass index, BMI, of 28) in their mid-60s with advanced knee OA and clinical evidence of synovitis, were equally randomized to receive up to 25 mg a week of oral MTX or placebo.

The researchers measured pain with the visual analogue pain scale (VAS) and assessed function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and activities of daily living (ADL) scores.

At the start and end of the trial, Doppler ultrasound and synovitis measured synovial thickness and knee effusion.

After 28 weeks, 130 patients had completed the trial. More than half (58%) of the MTX group had at least a 20 point reduction in VAS scores, as against about one-fourth of the placebo subjects. As a group the mean reduction in VAS (from 66.7 down  40.5) was significantly greater for subjects taking MTX than in the placebo group (mean VAS from 66.7 to VAS 51.7).

The MTX group also had significantly lower WOMAC pain and stiffness subscale scores, improvement in ADLs, and clinically relevant reductions in synovial thickness and knee effusion by the end of the trial.

Patients were allowed to continue their usual pain-relief medications as needed during the trial, and fewer in the MTX group used analgesics compared with those on placebo.

It’s now known that OA has an inflammatory component, with synovitis believed to play a dominant role in the development of pain, joint inflammation and cartilage destruction. Some effects resemble those of rheumatoid arthritis, the study authors note.

No serious adverse events occurred in the MTX group. Patients taking the drug were more likely to experience alopecia, mucositis, and gastrointestinal symptoms, but not significantly more than those on placebo.