Qualifications and considerations for MTX use
Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.
Dr. Nelson
Dr. Amanda E. Nelson
Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.
She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.
Nicolas Tourrenc
Dr. Ida K. Haugen
“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.
Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”
Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”
In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.”
While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.
The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.
Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.
Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial).
The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.