P3697 - Changes in Health-Related Quality of Life (HRQL), Cognitive Dysfunction and Worry Domains in Patients With MASLD and MASH Treated With Resmetirom

Zobair Younossi, MD, MPH¹, Fatema Nader, MBBS¹, Dominic Labriola, PhD², Rebecca Taub, MD², Andrei Racila, MS³, Maria Stepanova, PhD¹
1The Global NASH Council, Washington, DC; 2Madrigal Pharmaceuticals, West Conshohocken, PA; 3The Global NASH CouncilMS, Washington DC, DC

Introduction: MASLD patients can experience cognitive function (CF) and significant worry that can affect their HRQL.

Methods: Patients with MASLD or MASH were enrolled in 2 clinical trials of resmetirom (MAESTRO-NAFLD, MAESTRO-NASH). Patients had completed HRQL instruments (LDQoL and CLDQ-NAFLD) at baseline, Week 24 and 52 of treatment. Using patients’ data from both HRQL data, a surrogate CF was developed. We assessed changes in CF and worry domain scores before and after treatment with resmetirom.

Results: 2221 patients treated with resmetirom were included. Exploratory factor analysis was performed using all pertinent HRQL items. The distribution of factor loadings suggested 5 items for the new CF domain (4 items from LDQoL and 1 item from CLDQ-NAFLD). At baseline, multivariate analysis showed that female sex (OR = 0.71 (0.56-0.90) for male), history of depression (OR = 2.89 (2.29-2.65)), clinically overt fatigue (OR = 1.57 (1.11-2.23)), and higher liver stiffness (OR = 1.025 (1.008-1.042) per 1 kPa) (p< 0.05) were associated with low CF scores (the lowest quartile). Baseline factors associated with low Worry scores (more worrying) also included female sex (OR = 0.61 (0.48-0.77) for male), history of depression (OR = 1.60 (1.25-2.03)), and higher liver stiffness (OR = 1.033 (1.016-1.050) per 1 kPa) (p< 0.05). During treatment with resmetirom, non-cirrhotic patients receiving placebo in MAESTRO-NAFLD experienced a worsening in CF domain score [mean (95% CI) change from baseline to Week 24: -3.0 (-5.0 to -1.1); from baseline to Week 52: -2.3 (-4.3 to -0.2); both p< 0.05], while no similar decrease was observed in patients treated with 80 mg or 100 mg of resmetirom (all p >0.05). The changes in CF domain scores were similar in patients with and without treatment response to resmetirom in all subgroups (PDFF decrease of ≥30% from baseline in patients without cirrhosis, PDFF decrease ≥20% in patients with cirrhosis, histologic response of NASH resolution or fibrosis improvement in non-cirrhotic patients with serial biopsy assessments) (all p >0.05). On the other hand, noncirrhotic patients with PDFF response experienced improvements in Worry domain scores (up to +7%) which were greater than those seen in placebo or non-responders.

Discussion: Cognitive function and Worry domains are related constructs and capture different aspects of patient-reported outcomes affected by patient characteristics and treatment response in MASH.

Disclosures:
Zobair Younossi: Zobair M. Younossi is a consultant or has received research funding from Intercept, Cymabay, Boehringer Ingelheim, Ipsen, Gilead Sciences, Inventiva, – Consultant.
Fatema Nader indicated no relevant financial relationships.
Dominic Labriola: Madrigal Pharmaceuticals – Employee, Stock Options.
Rebecca Taub: Madrigal Pharmaceuticals – Employee, Stock Options, Stock-publicly held company(excluding mutual/index funds).
Andrei Racila indicated no relevant financial relationships.
Maria Stepanova indicated no relevant financial relationships.

Zobair Younossi, MD, MPH¹, Fatema Nader, MBBS¹, Dominic Labriola, PhD², Rebecca Taub, MD², Andrei Racila, MS³, Maria Stepanova, PhD¹. P3697 - Changes in Health-Related Quality of Life (HRQL), Cognitive Dysfunction and Worry Domains in Patients With MASLD and MASH Treated With Resmetirom, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.