Impact of Minimal Dose Strategy Before Antithyroid Drug Discontinuation on Relapse Risk in Graves’ Disease

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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 4 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 4352 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). Conclusion: 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.

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