The researchers reported that patients tolerated methotrexate well. No patients had serious adverse events from treatment, although 10% of the patients on the drug did discontinue it. Four patients also discontinued the placebo. The methotrexate and placebo groups had similar incidences of adverse events, none of which required change in medication dosage or dropping out of the study.
“Our results suggest that targeting inflammation is important and works, and that it can be done with a medication, such as methotrexate, that has a broader action than the more selective medications, such as the anti-TNF [agents], which have not worked,” says Dr. Cicuttini.
The paper notes study limitations. They include the low initial dose of methotrexate and failure to target the inflammatory phenotype of hand osteoarthritis, since only 29 of a possible 1,024 joints had evidence of synovitis, where an effect of methotrexate might be expected.
Using Methotrexate
Dr. Cicuttini says methotrexate is a well-tolerated treatment. The most common side effects are nausea and mouth ulcers, which can be reduced with use of the vitamin folic acid. However, using methotrexate does require blood monitoring to check for effects on the liver function or reduced white blood cells or platelets.
“Although it’s the most commonly used drug around the world for inflammatory arthritis, some of the methotrexate side effects are potentially serious and need monitoring. And that adds hassle for health systems, doctors, and patients, although most people cope with the side effects pretty well,” says Professor Philip Conaghan, MBBS, PhD, director, National Institute for Health and Care Research, Leeds Biomedical Research Centre, Leeds Teaching Hospitals, and professor of musculoskeletal medicine at University of Leeds, U.K.
“It would overwhelm health systems if we gave methotrexate to everyone with hand OA,” he says. “So you need a clear understanding of which subgroup of patients you should give it to. No one knows that very well yet.”
Dr. Conaghan adds that the study shows methotrexate works for hand OA pain, but it does not show significant improvement in function. Function primarily means grip strength, which relies on muscles, he explains. “This drug is never going to give you stronger muscles, so the drug does not remove the need to teach people exercises to get their function back.”
“For the first time in many years, in an imaging-proven inflammatory group of hand OA patients, we’ve seen a reduction in pain with methotrexate, full stop,” he says. “But it’s not feasible to send everyone off for MRIs and ultrasounds.” He called the study “clearly very important as a proof of concept,” and for more understanding of the subset of hand OA patients for whom methotrexate will be a useful, everyday clinical therapy.
