A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis

作者：Stephen A. Harrison, Pierre Bédossa, Cynthia D. Guy, Jörn M. Schattenberg, Rohit Loomba, Rebecca Taub, Dominic Labriola, Sam E. Moussa, Guy Neff, Mary E. Rinella, Quentin M. Anstee, Manal F. Abdelmalek, Zobair M. Younossi, Seth J. Baum, Sven Francque, Michael Charlton, Philip N. Newsome, Nicolas Lanthier, Ingolf Schiefke, Alessandra Mangia, Juan M. Pericàs, Rashmee Patil, Arun J. Sanyal, Mazen Noureddin, Meena B. Bansal, Naim Alkhouri, Laurent Castéra, Madhavi Rudraraju, Vlad Ratziu · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2309000 · 被引用次数：1835 · 研究领域：Liver Disease Diagnosis and Treatment、Liver Diseases and Immunity、Liver Disease and Transplantation

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed, thyroid hormone receptor beta-selective agonist in development for the treatment of NASH with liver fibrosis. METHODS: We are conducting an ongoing phase 3 trial involving adults with biopsy-confirmed NASH and a fibrosis stage of F1B, F2, or F3 (stages range from F0 [no fibrosis] to F4 [cirrhosis]). Patients were randomly assigned in a 1:1:1 ratio to receive once-daily resmetirom at a dose of 80 mg or 100 mg or placebo. The two primary end points at week 52 were NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points; scores range from 0 to 8, with higher scores indicating more severe disease) with no worsening of fibrosis, and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. RESULTS: Overall, 966 patients formed the primary analysis population (322 in the 80-mg resmetirom group, 323 in the 100-mg resmetirom group, and 321 in the placebo group). NASH resolution with no worsening of fibrosis was achieved in 25.9% of the patients in the 80-mg resmetirom group and 29.9% of those in the 100-mg resmetirom group, as compared with 9.7% of those in the placebo group (P<0.001 for both comparisons with placebo). Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% of th...