A previous study of methotrexate in hand OA found no benefit.3 But the study was in a subgroup of patients who had erosive OA—which involves cartilage damage and bone erosion in the hand joints—a different population from those described in the recent study, whose disease was not as advanced, Dr. Cicuttini noted. However, in her previous methotrexate trials and studies examining TNF-alpha inhibitors in hand OA, some evidence suggested reduced inflammation with less joint damage.
The Study
The randomized, double-blind, placebo-controlled trial assessed whether methotrexate given once a week reduced pain, compared to a placebo, and improved function in patients with symptoms of hand OA and synovitis.
The researchers followed patients taking methotrexate for six months to see whether they had significantly less pain and stiffness, compared with the placebo patients. Methotrexate patients took 10 mg by mouth once per week for the first four weeks and took 20 mg weekly in the same way for the rest of the study, plus folic acid to reduce drug side effects.
The primary outcome was pain measured by the visual analog scale (VAS), a well-established way to measure self-reported pain intensity. VAS consists of a 100 mm line, with two end points representing 0 ( or no pain) and 10 (for pain as bad as it could possibly be). Patients reported their current level of pain by placing a mark on the line.
The patients were recruited between 2017 and 2022, although the trial—intended originally as a two-year study—paused temporarily in 2020 due to the COVID-19 pandemic and concerns about potentially infected patients taking methotrexate. The study included 97 patients aged 40–75, 70% of whom were women. The participants had experienced pain in their hand joints most days for the previous three months. According to the paper, the patients’ VAS scores were at least 40 mm in the week prior to beginning participation. Patients had OA confirmed in at least one joint, and many had inflammation visible on magnetic resonance imaging (MRI). The researchers excluded patients with gout, psoriasis, evidence of rheumatoid arthritis (e.g., rheumatoid factor, the presence of anti-cyclic citrullinated peptides, elevated inflammatory markers), and patients who would be harmed by methotrexate or MRI.
After six months, patients who took methotrexate had less pain and lower VAS scores than those patients who took placebo. The mean reduction in VAS scores was 15.2 mm for the methotrexate group, vs. 7.7 mm for the placebo group. Additionally, the methotrexate patients had greater reductions in another pain index, the Australian Canadian (AUSCAN) Osteoarthritis Hand Index. But there were no differences in other secondary outcomes, including mean AUSCAN score, scores on two other pain assessments, and grip strength.
