Exploration of Multiple Non-Invasive Tests for Assessing Response to Treatment in a Semaglutide Phase 2b Trial in Patients With MASH.

Abstract

BACKGROUND Non-invasive tests (NITs) are not currently approved as biomarkers of treatment response for patients with metabolic dysfunction-associated steatohepatitis (MASH). AIM This retrospective study explored a panel of NITs for assessing response to semaglutide treatment in patients with MASH randomised in a phase 2b trial (NCT02970942). METHODS The present study was performed using the completer population (268 patients), defined as all patients who were randomised, remained on treatment throughout the trial, and had liver biopsy and NIT results at baseline and week 72. Semaglutide treatment arms were analysed as one semaglutide pooled group. Multiple NITs (alanine transaminase, aspartate transaminase [AST], controlled attenuation parameter, CK18-M30/M65, SomaSignal nonalcoholic steatohepatitis tests, FibroScan-AST, NIS-4, metabolomics advanced steatohepatitis fibrosis score, fibrosis-4 index, liver stiffness measure [LSM], enhanced liver fibrosis [ELF], PRO-C3 and ADAPT) were assessed. Treatment response was evaluated by NITs using either mean changes, responder groups, or risk categories from baseline to week 72. RESULTS Semaglutide treatment led to significant reductions versus placebo in all NIT scores from as early as 28 weeks. More patients had MASH improvement and fewer had fibrosis progression versus placebo when assessed by a 20% NIT response (0.5 U for ELF); among patients with baseline LSM > 8 kPa and ELF > 9.8 U, a larger proportion achieved LSM < 8 kPa and ELF < 9.8 kPa with semaglutide versus placebo. CONCLUSION NITs may be used for assessing a treatment response in patients with MASH. Further studies should confirm the treatment effect of NITs and evaluate the association of NIT changes to outcomes.