Adjunctive methotrexate also cut cumulative steroid exposure and increased the probability of achieving a sustained 24-week discontinuation of steroids (Arthritis Rheum. 2007;56:2789–97).
The meta-analysis had limitations, Dr. Mahr said, including small numbers of patients and short follow-ups. As with the PMR trial, there were no differences in adverse events between the treatment and control groups.
“Methotrexate could be considered as a therapeutic option for patients with GCA, particularly for those who are at high risk for corticosteroid-related adverse events,” Dr. Mahr said.
This conclusion has recently been affirmed in a recommendation from the European League Against Rheumatism: “A meta-analysis of these three trials demonstrates a modest role for methotrexate (10–15 mg/week) in reducing relapse rate and lowering the cumulative dose of glucocorticoid therapy. … We recommend that an immunosuppressive agent should be considered for use in large vessel vasculitis as adjunctive therapy” (Ann. Rheum. Dis. 2008 April 15 [doi:10.1136/ard.2008.088351]).
Following the presentation, Dr. Gary Hoffman of the Cleveland Clinic stated that he did not agree with the conclusions of the study, noting that there was “enormous heterogeneity” in terms of study design, and significant differences in methotrexate doses and in the timing of the addition of methotrexate. “And ultimately, even if you buy into the validity of the meta-analysis, you are still left with patients with no differences in corticosteroid-related or methotrexate-related adverse events,” said Dr. Hoffman, who is Harold C. Schott Chair of Rheumatic and Immunological Diseases and professor of medicine at Case Western Reserve University, Cleveland.
He went on to say, “Given that we know methotrexate can cause problems such as pneumonitis, which can sometimes be a fatal disease, and that pneumonitis can occur in 1%–5% of patients who are treated with methotrexate, there may not have been enough patients in the individual studies to identify those one or two who might be affected. With just one such patient in the methotrexate group, our view of the outcome would be considerably different,” he said.
In a subsequent interview, session cochair Dr. Robert F. Spiera of Cornell University, New York, said that although there may be some justification for the use of methotrexate in these conditions, “it clearly is not the standard of care.”
“There has never been an unequivocally powerful signal for efficacy, and if you have to treat 11 or 12 patients to prevent one relapse, you are giving methotrexate to a lot of older patients who could have adverse events,” said Dr. Spiera, also director of the scleroderma and vasculitis program at the Hospital for Special Surgery, New York.