Methotrexate lowers pain in inflammatory hand OA

In a placebo-controlled study, therapy with methotrexate led to a clinically significant reduction of pain and stiffness in participants with osteoarthritis (OA) of the inflammatory phenotype. Methotrexate could become a novel, economical treatment possibility for these difficult-to-treat patients.

At present, limited therapeutic options are available for hand OA. A previous randomised-controlled trial showed no superiority of methotrexate 10 mg over placebo in pain relief at 3 or 12 months in participants with erosive hand OA [1]. However, as Prof. Flavia Cicuttini (Monash University, Australia) pointed out, hand OA is a heterogeneous disease, and no previous study has examined methotrexate in hand OA targeting the inflammatory subtype. “Our aim was to determine whether methotrexate reduced pain and improved function over 6 months in participants with hand OA and synovitis,” she explained [2].

This multicentre, double-blind, randomised-controlled trial included participants with radiological OA in ≥1 joint and non- gadolinium MRI-detected synovitis, who were treated with methotrexate 20 mg/week or placebo plus folic acid 5 mg on other days. The primary outcome was pain reduction (assessed by a 100 mm visual analogue scale [VAS]) at 6 months.

Baseline characteristics were typical for an OA population with a medium age of 60 and a female preponderance. Regarding the primary study endpoint, there was an improvement in pain in both groups until week 4, but methotrexate kept reducing this symptom, whereas there was a plateau in the VAS in the placebo group (see Figure). At 6 months, the methotrexate group had a greater reduction in VAS pain than the placebo group (-15.2 vs -7.7; difference -9.9; 95% CI -19.3 to 0.6). “When we calculated the effect size, VAS pain was 0.45, which puts it into a moderate effect,” Prof. Cicuttini explained. In addition, therapy with methotrexate also led to a distinct improvement in stiffness. Methotrexate was safe and well tolerated. The study's limitations were that it was initially planned to assess methotrexate's effect on pain and radiographic progression over 2 years. However, all medication ceased in March 2020 due to uncertainty regarding the safety of methotrexate during the COVID-19 pandemic.

All in all, this study is proof of concept that methotrexate may have a role in the management of hand OA with the inflammatory phenotype. “Studies of longer duration including assessment of structural modification are warranted to see whether methotrexate has a disease-modifying effect as well,” Prof. Cicuttini concluded.

Figure: VAS pain at each time point over the study period [2]



VAS, visual analogue scale.

1. Ferrero St, et Semin Arthritis Rheum. 2021;51:831-8.
2. Cicuttini F, et METHODS - A randomized controlled trial of METhotrexate to treat Hand Osteoarthritis with Synovitis. OP0070, EULAR 2023, 31 May–3 June, Milan, Italy.

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Posted on 31 July, 202331 July, 2023