Objective: The optimal treatment regimen with thionamide drugs remains a matter for debate. We have investigated whether high doses of carbimazole, when compared with low doses, reduce relapse rates of Graves' disease.
Design: In an open label, randomized, prospective trial of treatment of Graves' disease we compared high doses of carbimazole (6 months of 100 mg carbimazole per day plus thyroxine) to low-dose carbimazole treatment (starting at 25 mg and titrating the carbimazole dose with the aim to maintain serum thyroid function test results within the normal reference range).
Patients: Thirty-seven patients with a first episode of Graves' disease were enrolled.
Measurements: During the 6 months of treatment we evaluated the rate of normalization of serum thyroid function tests, changes in serum thyroid auto-antibody levels and the rate of side-effects during treatment. After completion of the 6-month treatment course patients were observed for 2 years for evidence of relapse of Graves' disease.
Results: There were no differences between the two groups either in the rate of normalization of serum thyroid function tests or in serum thyroid auto-antibody levels during treatment. Of the 17 patients randomized to high-dose treatment seven suffered treatment side-effects, compared to only one of the 20 patients receiving low-dose treatment (P < 0.006). There was no significant difference in 2-year post-treatment remission rates on an intention-to-treat basis between the two treatment groups (18.7% vs. 5.9%, P = NS). However, for those patients who completed 6 months of treatment (high-dose group = 9, low-dose group = 16), multivariate survival analysis demonstrated a significantly longer median relapse-free interval (P < 0.04) in the high-dose group (27 weeks; 25th percentile: 9.6 weeks, 75th percentile: 75 weeks) versus the low-dose group (6 weeks; 25th percentile: 4.8 weeks, 75th percentile: 13.1 weeks).
Conclusions: High-dose carbimazole treatment delays, but does not prevent, relapse from Graves' disease in those patients able to tolerate the treatment. However, it leads to more frequent side-effects than conventional dose treatment.