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

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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: = 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.

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