Vasculitis
Abstract 439: Adjunctive Methotrexate to Treat Giant Cell Arteritis: An Individual Patient Data Meta-Analysis
Authors: Alfred D. Mahr, Gary S. Hoffman, Juan A. Jover, Robert F. Spiera, Cesar Hernandez-Garcia, Benjamin Fernandez-Gutierrez, Michael P. LaValley, Peter A. Merkel
Background: Giant cell arteritis is a large vessel vasculitis that can have multiple manifestations, including claudication, polymyalgia rheumatica, fever of unknown origin, and visual loss. Standard therapy for giant cell arteritis utilizes high doses of glucocorticoids for a prolonged period of time. While efficacious, this treatment strategy subjects patients to the untoward effects of glucocorticoids, which has led investigators to seek other options. Three randomized clinical trials studying the use of adjunctive methotrexate (in addition to glucocorticoids) for the treatment of giant cell arteritis have yielded conflicting results. This study reports the results of a combined analysis of the primary data from these 3 studies.
Study Design: This is a pooled analysis of randomized clinical trials of giant cell arteritis led by Gary Hoffman, Juan Jover, and Robert Spiera, who released the primary data from their clinical trials for this study. All patients were initially treated with high dose glucocorticoids, and were randomized to receive either placebo or methotrexate (in doses ranging from 7.5 to 20 mg per week; mean dose: 11 mg). Outcome measures studied included first and second relapse rates, cumulative glucocorticoid exposure, time to discontinuation of glucocorticoids, and adverse event rates.
Results: The pooled dataset included 161 patients, 84 of whom received methotrexate. The overall first relapse rate was 71%; the overall second relapse rate was 35%. The hazard ratio for first relapse among those treated with methotrexate was 0.64 (95% confidence interval (CI) 0.43-0.96), representing a 36% risk reduction; the hazard ratio for second relapse among those treated with methotrexate was 0.49 (95% CI 0.27-0.88), representing a 51% risk reduction. Treatment with methotrexate did not lead to an increase in infection or adverse events. The number needed to treat to prevent one relapse was 3.6. Methotrexate significantly increased the probability of remaining off of glucocorticoids for 6 months or longer (HR 2.84; P=0.001).
Editorial Comments: It is ironic that the elderly patients who are most likely to develop giant cell arteritis are also the least likely to tolerate the high dose glucocorticoids required to treat it. Unlike the traditional meta-analysis, this study combined and re-analyzed the primary data generated by these 3 studies, more closely mimicking what might have occurred in one large study. The heterogeneity in study protocols, especially with regard to glucocorticoid taper and methotrexate dosage, is concerning, although no statistically significant difference was detected in treatment effect among the 3 trials. Overall, the results of this study support the routine use of methotrexate for the treatment of giant cell arteritis. It would have been interesting to know if there is a threshold dose for methotrexate (i.e., if patients treated with higher doses received more benefit than those treated with lower doses), although the total number of patients in this analysis was too small to permit such an analysis. Many of us who have used methotrexate in our clinical practice have not noticed a dramatic effect; however, it seems reasonable to consider methotrexate as an adjunctive therapy, especially for patients who have specific contraindications to prolonged treatment with glucocorticoids.