There seems to be both hope and uncertainty regarding the use of weekly methotrexate in giant cell arteritis (GCA) patients who need to limit their glucocorticoid use. While well done clinical trials have shown no certain efficacy, data suggesting methotrexate benefits come from small trials, anecdotal experience, and clinical experience.
One of the earliest and best done trials of methotrexate in GCA was in 2002 and enrolled 98 patients, temporal artery biopsy proven (about 80%), who were started on prednisone and methotrexate (15 mg/week) or placebo. The researchers found the frequency of treatment failure (relapses) to be comparable after 12 months: 57.5% for methotrexate versus 77.3% for placebo (P=0.26). Methotrexate was therefore not associated with a reduced risk of treatment failure (relative risk 0.72, 95% CI 0.41-1.28).
Patients diagnosed with GCA from 1998 to 2013 with confirmed evidence of temporal artery biopsy and/or radiographic evidence of large vessel vasculitis were identified. Each patient with GCA treated with adjunct methotrexate (case) was matched to a similar patient with GCA treated only with glucocorticoid (control), glucocorticoid requirements and relapse events before and after methotrexate initiation (or corresponding index date) were compared using rate ratios (RR).
Another recent “real-world” trial matched 83 GCA patients, treated with methotrexate plus glucocorticoid-treated patients against 83 glucocorticoid-only patients (controls). The outcomes and flare rates compared. The time from GCA diagnosis to methotrexate initiation was 39 (13-80) weeks and the median dose was 13.5 (10-15) mg/week.
When the researchers examined future relapse rates before and after methotrexate initiation, they found significantly reduced rates in both cases (RR 0.32, 95% CI 0.24-0.41) and controls (RR 0.60, 95% CI 0.43-0.86). The decrease in relapse rate was significantly greater in patients taking methotrexate than in those taking glucocorticoid alone (P=0.004). Steroid use and discontinuation did not differ between groups.
From this single-institution, observational study, the addition of methotrexate to glucocorticoid appeared to decrease the rate of subsequent relapse by nearly two-fold compared with patients taking glucocorticoid alone.
However, note that “real-world” data should be interpreted cautiously, as these are not proof, but only capable of raising interesting postulates that require more rigorous testing or trials.
Jack Cush, MD, is the director of clinical rheumatology at the Baylor Research Institute and a professor of medicine and rheumatology at Baylor University Medical Center in Dallas. He is the executive editor of RheumNow.com. A version of this article first appeared on RheumNow, a news, information, and commentary site dedicated to the field of rheumatology. Register to receive their free rheumatology newsletter.