A Common, Low-Cost Drug May Have a Role in Managing Symptomatic Hand OA

A study from Australia has found that methotrexate – the low-cost, effective treatment for inflammatory joint conditions such as rheumatoid arthritis and psoriatic arthritis – may be effective in managing osteoarthritis (OA) of the hand.

The study was published online ahead of print by The Lancet.

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The researcher group reported that a 20-mg weekly oral dose of methotrexate over a 6-month period “had a moderate but potentially clinically meaningful effect in reducing pain” and stiffness in patients with symptomatic hand OA.

Role of Inflammation

Senior author Professor Flavia Cicuttini, who heads the Musculoskeletal Unit at Monash University’s and is the Head of Rheumatology at The Alfred Hospital, both in Melbourne, Australia, said the study identified the role of inflammation in hand OA and the potential benefit of targeting patients who experience painful hand OA.

“In our study, as with most studies of osteoarthritis, both the placebo group and methotrexate groups’ pain improved in the first month or so,” Professor Cicuttini said.

“However, pain levels stayed the same in the placebo group but continued to decrease in the methotrexate group at 3 and 6 months, when they were still decreasing. The pain improvement in the methotrexate group was twice as much as in the placebo group.

“Based on these results, use of methotrexate can be considered in the management of hand osteoarthritis with an inflammatory pattern. This provides clinicians with a treatment option for this group, which tends to get more joint damage.”

Study Group

For this randomized, double-blind, placebo-controlled trial, researchers recruited participants from Melbourne, Hobart, Adelaide, and Perth in Australia who had hand OA (Kellgren and Lawrence grade ≥2 in at least 1 joint) and grade 1 or more synovitis on MRI.

The 97 participants were randomized on a 1:1 basis to receive either 20 mg of methotrexate (n=50) or a placebo (n=47) orally once a week for 6 months. Most participants were women (70%).

Future Research

Professor Cicuttini said the study results could offer the opportunity for symptomatic relief for people with hand OA inflammation, which was particularly common in women as they experienced menopause.

“Further trials are needed to establish whether the effect of methotrexate extends beyond 6 months, for how long we need to treat patients, and whether methotrexate reduces joint damage in patients with hand osteoarthritis and associated inflammation,” she said.

Professor Cicuttini now plans to conduct an extension trial to address these questions, in particular whether women who develop hand OA around menopause and often have severe pain and joint damage may benefit.


Wang Y, Jone G, Keen HI, et al. Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial. Lancet. 2023 Oct 12:S0140-6736(23)01572-6. doi: 10.1016/S0140-6736(23)01572-6. Online ahead of print.

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