Endocrine Abstracts

JOINT1316

Background: Cessation of methimazole treatment in Graves’ Disease (GD) often leads to relapse. In February 2023, Clalit Healthcare Services (CHS), the largest health maintenance organization in Israel, began to provide thyrotropin receptor antibody (TRAb) testing for patients with GD to help guide when to withdraw methimazole treatment. This nationwide retrospective cohort study evaluated whether using TRAb testing to guide methimazole withdrawal reduces relapse rates compared to clinical judgment alone.

Methods: Using the MDClone platform, we identified CHS-insured patients diagnosed with GD between 01/2013 and 09/2023. The first day of remission was established three months following the last purchase of methimazole if euthyroid or hypothyroid thyroid function test results were documented during this timeframe. Exclusion criteria included prior thyroidectomy or radioactive iodine treatment, pregnancy, and elevated liver transaminases (≥3 times the upper limit of normal), or neutropenia (≤1,000 × 10³/µL) within six months of methimazole cessation. Patients were grouped into two cohorts; one where TRAb titer was tested and measured <2.5 Ul/l (seronegative) within three months of the last purchase of methimazole (‘TRAb assisted cohort’), and one where TRAb was not measured in this time period (‘clinical assessment cohort’). Baseline characteristics and the primary outcome - GD early relapse, defined as subsequent thyrotoxicosis during one-year follow-up were compared. A frailty Cox regression assessed the association between TRAb seronegative status immediately prior to methimazole cessation and disease relapse, adjusting for potential confounders.

Results: The study included 3420 clinical episodes; 84 in the TRAb assisted cohort and 3336 in the clinical assessment cohort. Age (median 49 years, P = 0.47), gender (75% female, P = 0.8) and socioeconomic status (score of 3 when using a five-point scale, P = 0.46) were similar in the two cohorts. At the time of GD diagnosis, free triiodothyronine (T3) was above the upper limit of normal in 73% of patients in the TRAb assisted cohort and 66% in the clinical assessment cohort (P = 0.4). The proportion of patients with TSH above or within the normal range prior to methimazole cessation was similar (87% in both cohorts, P >0.99). During one-year follow-up, 49/84 (55%) in the TRAb assisted cohort and 2606/3336 (78%) patients in the clinical assessment cohort relapsed (P = 0.002). TRAb seronegative status prior to stopping methimazole reduced the risk of relapse by 38% compared to clinical assessment alone (HR 0.62, CI 0.46-0.84, P = 0.002).

Conclusion: Seronegative TRAb status reduces the one-year relapse risk by 38% amongst patients presumed to be in remission.