Effects of low-dose methotrexate with MMI in patients with Graves’ disease: results of a randomized clinical trial

Abstract Context Supplemental methotrexate (MTX) may affect the clinical course of Graves’ disease (GD). Objective To evaluate the efficacy of add-on MTX on medical treatment in GD. Design Prospective, open-label, randomized supplementation controlled trial. Setting Academic endocrine outpatient clinic. Patients One hundred fifty-three untreated hyperthyroid patients with GD. Intervention Patients received MTX 10 mg/w with methimazole (MMI) or MMI only. MTX and MMI were discontinued at months 12 to 18 in euthyroid patients. Main Outcome Measures Discontinuation rate at month 18 in each group. Results In the MTX with MMI group, the discontinuation rate was higher than the MMI group at months 15 to 18 [50.0 vs 33.3%, P = .043, 95% confidence interval (CI) 1.020-3.922; and 55.6 vs 38.9%, P = .045, 95% CI 1.011-3.815, respectively). The decrease in thyrotropin-related antibodies (TRAb) levels in the MTX with MMI group was significant from baseline to month 6 compared to the MMI alone group [MTX + MMI 67.22% (43.12-80.32), MMI 54.85% (33.18-73.76), P = .039] and became more significant from month 9 [MTX + MMI 77.79% (62.27-88.18), MMI 69.55% (50.50-83.22), P = .035] to month 18 (P < .01 in 15-18 months). A statistically significant difference was seen between the levels of TRAb in the MTX with MMI group and the MMI group at 9 to 18 months. There were no significant differences in the levels of free T3, free T4, and TSH between the 2 groups. No serious drug-related adverse events were observed in either group (P = .771). Conclusion Supplemental MTX with MMI resulted in a higher discontinuation rate and improvement in decreased TRAb levels to homeostatic levels faster than methimazole treatment alone at months 12 to 18.