Methotrexate treatment in hand osteoarthritis with synovitis

Hand osteoarthritis (OA) can be disabling and severely affects the quality of life. About 500 million individuals worldwide are affected by OA and it is the fourth leading cause of disability globally.

A groundbreaking study conducted by Monash University and Alfred Health, has found that methotrexate, a low-cost drug that has been used since the 1980s to treat inflammatory joint conditions such as rheumatoid arthritis and psoriatic arthritis, has shown moderate effectiveness in relieving pain and stiffness in patients with symptomatic hand OA.

The randomized, double-blind, placebo-controlled trial involving 97 participants determined whether 20 mg of methotrexate taken weekly could reduce the pain and improve function compared to placebo in patients with symptomatic hand OA and synovitis (inflammation) over six months. The participants were recruited from Melbourne, Hobart, Adelaide, and Perth, and the trial was conducted with the support of the National Health and Medical Research Council (NHMRC).

The study conducted by Wang et al. revealed that methotrexate is a viable treatment option for hand OA with an inflammatory pattern. Both the placebo and methotrexate groups experienced pain relief during the first month of treatment. However, only the methotrexate group exhibited sustained pain reduction at three and six months, showing twice the improvement compared to the placebo group.

An open-label study by Wenham et al. evaluated the efficacy of oral methotrexate for painful knee OA using contemporary dosing and has revealed a considerable number of participants experiencing a significant reduction in pain. This reduction is on par with the pain relief typically achieved using widely prescribed NSAIDs. and it is also comparable to the average pain reduction associated with opioids.

The study findings hold promise for alleviating the suffering of individuals dealing with inflammation in hand OA. Further trials are warranted to ascertain if methotrexate can effectively reduce joint damage in patients with OA and concurrent inflammation, to determine the optimal duration of treatment, and to explore whether the benefits of methotrexate persist beyond a six-month timeframe.


  1. Wang Y, Jones G, Keen HI, Hill CL, Wluka AE, Kasza J, et al. Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomized, placebo-controlled trial. The Lancet [Internet]. 2023 Oct 12 [cited 2023 Oct 20];0(0).
  2. Wenham CYJ, Grainger AJ, Hensor EMA, Caperon AR, Ash ZR, Conaghan PG. Methotrexate for pain relief in knee osteoarthritis: an open-label study. Rheumatology. 2013 May 1;52(5):888–92.
  3. Yao Q, Wu X, Tao C, Gong W, Chen M, Qu M, et al. Osteoarthritis: pathogenic signaling pathways and therapeutic targets. Sig Transduct Target Ther. 2023 Feb 3;8(1):1–31.