Effects of Low-dose Methotrexate With Methimazole in Patients With Graves' Disease: Results of a Randomized Clinical Trial.

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.