MTX plus MMI for Graves’ disease tied to higher discontinuation rate vs MMI alone

The addition of low-dose methotrexate (MTX) to methimazole (MMI) shows a higher rate of discontinuation than MMI alone, as well as significant reductions in thyrotropin-related antibodies (TRAb) levels, in patients with Graves’ disease (GD), reveals a study.

A total of 153 untreated hyperthyroid patients with GD were included in this prospective, open-label, randomized controlled trial conducted in an academic endocrine outpatient clinic. Participants received either MTX 10 mg/w with MMI or MMI alone. In euthyroid patients, MTX and MMI were discontinued at months 12 to 18.

The discontinuation rate was higher in the MTX plus MMI group than the MMI only group at months 15 to 18 (50.0 percent vs 33.3 percent; p=0.043; and 55.6 percent vs 38.9 percent; p=0.045, respectively).

A significant decrease in TRAb levels was observed in the MTX plus MMI group from baseline to month 6 relative to that in the MMI only group (67.22 percent vs 54.85 percent; p=0.039). This reduction became more significant from month 9 (77.79 percent vs 69.55 percent; p=0.035) to month 18 (p<0.01 in 15–18 months).

A statistically significant difference was observed between TRAb levels in the MTX plus MMI group and the MMI only group at 9 to 18 months. On the other hand, no significant between-group differences were noted in the levels of free T3, free T4, and TSH.

Of note, serious drug-related adverse events did not occur in either group (p=0.771).

“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,” the researchers said.