Methotrexate to Treat Osteoarthritis of the Hand with Synovitis (METHODS) an Australian, Multicentre, Parallel Group, Double-Blind, Randomized, Placebo-Controlled Trial Summary Background Osteoarthritis of the hand is a disabling condition with few effective therapies. Osteoarthritis of the hand with synovitis is a common inflammatory phenotype associated with pain. Our objective was to examine the efficacy and safety of methotrexate at 6 months in participants with osteoarthritis and synovitis of the hand. Methods In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, participants (aged 40 to 75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and hand synovitis degree detected by MRI. 1 or more were recruited from the community in Melbourne, Hobart, Adelaide and Perth, Australia. Participants were randomly assigned (1:1) using block randomization, stratified by study site and self-reported sex, to receive 20 mg of methotrexate or an identical placebo orally once a week for 6 months . The primary outcome was pain reduction (measured with a 100-mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were evaluated in all randomized participants. This trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12617000877381). Results Between November 22, 2017 and November 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were women and 29 (30%) were men. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was –15.2 mm (SD 24.0) in the methotrexate group and –7.7 mm (25.3) in the placebo group, with a difference mean between groups of – 9.9 (95% CI –19.3 to –0.6; p=0.037) and an effect size (standardized mean difference) of 0.45 (0.03 to 0.87) . Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group. Interpretation Treatment of osteoarthritis and synovitis of the hand with 20 mg of methotrexate for 6 months had a modest but potentially clinically significant effect on pain reduction, providing proof of concept that methotrexate could have a role in the treatment of hand osteoarthritis and synovitis. Osteoarthritis of the hand with an inflammatory phenotype. Money National Health and Medical Research Council of Australia. |
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Relief could be on the way for people with painful hand osteoarthritis after a study led by Monash University and Alfred Health found an existing, affordable drug can help. Until now there has been no effective treatment.
Published in The Lancet , the paper investigated methotrexate , an effective, low-cost treatment for inflammatory joint conditions such as rheumatoid arthritis and psoriatic arthritis. It has been used widely in Australia and around the world since the early 1980s.
Researchers found that methotrexate reduced symptoms in people with hand osteoarthritis (OA). A weekly oral dose of 20 mg for six months had a moderate effect on reducing pain and stiffness in patients with symptomatic hand OA.
Hand OA is a disabling condition that causes pain and affects function, preventing daily activities such as dressing and eating. It can significantly reduce quality of life. About one in two women and one in four men will experience symptoms of hand OA by the time they turn 85.
About half will have swollen joints, which causes pain and is associated with significant joint damage. Despite the high prevalence and burden of disease, there are no effective medications.
Lead author Professor Flavia Cicuttini, Director of the Musculoskeletal Unit at Monash University and Head of Rheumatology at The Alfred, said the study identified the role of inflammation in hand OA and the potential benefit of focusing on patients experiencing painful OA in the hand.
"In our study, as in most osteoarthritis studies, pain in both the placebo and methotrexate groups improved within approximately the first month," Professor Cicuttini said. “However, pain levels remained the same in the placebo group, but continued to decrease in the methotrexate group at three and six months, when they were still decreasing. The improvement in pain in the methotrexate group was twice that of the placebo group.”
“Based on these results, the use of methotrexate can be considered in the treatment of hand osteoarthritis with an inflammatory pattern . “This provides doctors with a treatment option for this group, who tend to suffer more joint damage.”
Professor Cicuttini said that in patients with hand osteoarthritis and inflammation, the effects of methotrexate were present at around three months and by six months it was very clear whether it worked.
"At that point, patients and their doctors can decide whether to continue treatment or stop it," he said. "This is very similar to what we currently do with other forms of inflammatory arthritis."
The NHMRC-funded randomized, double-blind, placebo-controlled trial of 97 people evaluated whether 20 mg of methotrexate per week reduced pain and improved function compared to placebo in patients with symptomatic hand OA and synovitis. (inflammation) for six months.
Participants were recruited from Melbourne, Hobart, Adelaide and Perth with hand OA and inflammation detected by MRI. Professor Cicuttini said the results could provide relief to people with hand OA inflammation, which was particularly common in women when they were experiencing menopause.
"Further trials are needed to establish whether the effect of methotrexate extends beyond six months, how long we should treat patients, and whether methotrexate reduces joint damage in patients with hand osteoarthritis and associated inflammation," said.
Professor Cicuttini now plans to conduct an extension trial to address these questions, particularly whether women who develop hand OA around menopause and who often have severe pain and joint damage may benefit.
