Impact of minimal dose strategy before anti-thyroid drug discontinuation on relapse risk in Graves’ disease

Abstract Background Although antithyroid drugs (ATDs) are widely used as the first-line therapy for Graves’ disease, relapse after treatment discontinuation remains common. While a prolonged low-dose ATD therapy has been associated with improved remission rates, the impact of the minimal maintenance dose before discontinuation on relapse risk remains unclear. Method We conducted a retrospective cohort study using electronic medical records from a thyroid specialty hospital in Japan. Patients newly diagnosed with Graves’ disease between 2008 and 2024 who had discontinued methimazole (MMI) after receiving a minimal maintenance dose (≤2.5 mg/day) were included. Patients were categorized into four groups based on their final maintenance dose before discontinuation: 2.5 mg/day, 1.25 to ≤2.5 mg/day, 1.25 mg/day, and 1.25 mg/day. We evaluated the association between the minimal MMI dose before discontinuation and the 1-year risk of relapse using multivariable regression and propensity score–matched analyses. Results Among 4,352 eligible patients, multivariable regression showed that, compared with the 2.5 mg/day group, the 1.25 mg/day group had a significantly lower risk of relapse within 1 year (risk ratio RR 0.46, 95% confidence interval CI 0.28–0.75), and the 1.25 mg/day group had the lowest risk (RR 0.18, 95% CI 0.05–0.73). The propensity score-matched analysis, consistent with the multivariable regression, showed that the 1.25 mg/day group had a lower risk of relapse compared with the 2.5 mg/day group (RR 0.44, 95% CI 0.23–0.85; 172 matched pairs). Conclusions Lower minimum maintenance doses of MMI before discontinuation, particularly doses 2.5 mg/day, may be associated with a reduced risk of relapse in patients with Graves’ disease. Clinicians should recognize the clinical relevance of the minimum maintenance dose in the treatment of Graves’ disease.