Shorter Versus Standard Antithyroid Drug Therapy in Graves’ Disease with Lower Baseline Thyrotropin Receptor Antibody (TRAb) Levels: Relapse Outcomes from a Propensity-Weighted Analysis

Background: The optimal duration of antithyroid drug (ATD) therapy in Graves’ disease is uncertain. Although guidelines recommend 12–18 months, shorter courses may be sufficient in selected patients. We evaluated whether ATD duration <12 months is non-inferior to 12–18 months for relapse among patients with Graves’ disease and lower thyrotropin receptor antibody (TRAb) levels (>1.8 and <10.0 U/L) at diagnosis. Methods: We analyzed real-world data from adults with Graves’ disease and baseline TRAb <10 U/L treated with ATDs at a single center. The primary endpoint was relapse within 12 months of ATD cessation. A prespecified risk-difference non-inferiority framework was used, with a primary margin of +5% and an exploratory margin of +10%. Treatment effects were estimated using unadjusted analyses, inverse-probability-of-treatment weighting (IPTW; n = 369), and 1:1 propensity-score matching (PSM; 104 matched pairs). Secondary outcomes included long-term relapse (median follow-up 58 months), TRAb levels at cessation, and restricted mean survival time (RMST) over 60 months. Findings: At 12 months, relapse occurred in 23/134 (17.2%) patients treated <12 months and 48/235 (20.4%) treated for 12–18 months. The IPTW-adjusted risk difference was –1.5% (CI –11.0 to +8.0), meeting the 10% but not the 5% non-inferiority margin. The unadjusted estimate (–3.2%) met both margins, whereas the PSM estimate (+2.9%, CI –7.3 to +13.1) met neither because of reduced precision. Long-term outcomes were similar between groups (IPTW Cox HR 0.92 [CI 0.65–1.31]; RMST difference +3.2 months over 60 months [–2.1 to +8.4]). TRAb levels at cessation were comparable. Conclusions: Among patients with Graves’ disease and lower TRAb levels, shorter ATD courses (<12 months) produced outcomes broadly comparable to 12–18 months. Although strict non-inferiority was not confirmed at a 5% margin, findings meeting an exploratory 10% threshold support TRAb-guided individualization of ATD duration and justify prospective randomized evaluation.