Methotrexate vs Azathioprine in Second-line Therapy of Sarcoidosis

Background: Steroids remain the first-choice therapeutic in sarcoidosis; however, long-term use is associated with toxicity. Evidence defining the best second-line therapeutic is currently lacking. The aim of this study was to compare the effect of methotrexate and azathioprine on prednisone tapering, pulmonary function, and side effects in the second-line treatment of sarcoidosis. Methods: An international retrospective cohort study was performed, reviewing all patients with sarcoidosis who started methotrexate or azathioprine until 2 years after initiation or discontinuation. A linear mixed model with FEV1, vital capacity (VC), diffusing capacity of lung for carbon monoxide (D-LCO), and prednisone dose changes over time as end points was used. Side effects were compared with x 2 tests. Results: Two hundred patients were included, of whom 145 received methotrexate and 55 azathioprine. Prednisone daily dose decreased a mean of 6.32 mg/y (P<.0001) while on therapy, with a similar steroid-sparing capacity for methotrexate and azathioprine. Of all patients completing 1 year of therapy, 70% had a reduction in daily prednisone dose of at least 10 mg. FEV1 showed a mean increase of 52 mL/y (P = .006) and VC of 95 mL/y (P = .001) in both treatment groups. D-LCO % predicted increased, with a mean of 1.23%/y (P = .018). There were more patients with infections in the azathioprine group (34.6% vs 18.1%, P = .01), but no differences regarding other side effects. Conclusions: This retrospective study comparing the effect of second-line therapy in sarcoidosis shows that both methotrexate and azathioprine have significant steroid-sparing potency, a similar positive effect on lung function, and comparable side effects, except for a higher infection rate in the azathioprine group.