1806-P: Evaluating the Effect of Resmetirom on Thyroid Function: A Post Hoc Analysis of MAESTRO-NASH, a Phase 3 Randomized Controlled Study in Patients with MASH and Fibrosis

Introduction and Objective: Resmetirom (RES) is an liver-directed, thyroid hormone receptor-β agonist approved for treating adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced (F2-F3) liver fibrosis. Given the mechanism of action, we evaluated effects of RES on systemic thyroid function as measured by free thyroxine (fT4), free triiodothyronine (fT3), and thyroid-stimulating hormone (TSH). Methods: In the MAESTRO-NASH study, 966 patients were randomized 1:1:1 to RES 80 or 100 mg or placebo. Patients with untreated clinical or active subclinical hypothyroidism (TSH >10 IU/L without symptoms or TSH >7 IU/L with symptoms) were excluded; patients with asymptomatic subclinical hypothyroidism and those with thyroidectomy receiving stable replacement thyroxine doses >75 µg/d were allowed. As exploratory endpoints, fT4, fT3, TSH, and rT3 levels were analyzed through 52 RES initiation. Results: Overall, 830 patients with available data were included in this analysis. Baseline characteristics were similar to the primary analysis population and across the 3 cohorts. Changes in fT4, fT3, TSH, and rT3 over 52 weeks were generally small and comparable across all treatment groups; no clinically meaningful differences were observed. Conclusion: In this post hoc analysis, RES did not affect systemic thyroid function, providing further support of extrahepatic safety. Disclosure F. Tacke: Consultant; Current; Madrigal Pharmaceuticals, Inc., Novo Nordisk, Boehringer Ingelheim International GmbH, AstraZeneca. Speaker's Bureau; Current; Medscape. Consultant; Current; AstraZeneca, Ipsen Biopharmaceuticals, Inc. Other - DSMB member; Current; Sanofi. K.J. Miller: Employee; Current; Madrigal Pharmaceuticals, Inc. T.E. Alexander: Employee; Current; Madrigal Pharmaceuticals, Inc. G.A. Rezvani: Employee; Current; Madrigal Pharmaceuticals, Inc. Employee; Ended; Moderna, Inc.