Zobair Younossi, MD, MPH: Resmetirom’s Impact on Health-Related Quality of Life in MASH

New patient-reported outcomes data from the phase 3 MAESTRO-NASH trial highlight resmetirom (Rezdiffra)’s positive impact on health-related quality of life (HRQoL) in patients with metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced fibrosis, building upon previous findings regarding the liver-directed thyroid hormone receptor-β agonist’s benefit for MASH resolution and fibrosis improvement.^1,2

“[MASH] is a disease that does have an impact on quality of life, specifically health-related quality of life. In that context, the more severe the disease is, the more profound the quality of life impairment,” Zobair Younossi, MD, MPH, professor and chairman of the Beatty Liver and Obesity Research Program, Inova Health System, chairman of the Global NASH Council, and lead author of the HRQoL analysis, explained to HCPLive, describing misconceptions about MASH being an asymptomatic disease.

Younossi emphasized the importance of exploring any intervention’s “comprehensive impact,” including its clinical impact, its impact on patient experience and HRQoL, and its cost-effectiveness.

As the first and only FDA-approved MASH therapeutic, resmetirom’s clinical impact has been demonstrated across 18 studies in its clinical development program. Now, its benefit on patient experiences and HRQoL has also been confirmed through a MAESTRO-NASH analysis comparing changes in HRQoL scores from baseline in patients receiving resmetirom versus placebo and between patients with and without biopsy response.^1,2

Among 966 ITT patients, 323 received resmetirom 100 mg, 322 received resmetirom 80 mg, and 321 received placebo. By weeks 24 and 52, patients receiving 80 or 100 mg resmetirom experienced HRQoL improvement in the Worry domain of the Chronic Liver Disease Questionnaire-NASH (mean +0.21 to +0.24; P <.05). At week 52, participants who met histologic endpoints after treatment with resmetirom 100 mg or 80 mg experienced an improvement in several HRQoL domains, including Worry (+0.46), Health Distress (+8.1), and Stigma (+3.5).³

Of note, the improvement in HRQoL among resmetirom biopsy responders was contrasted by a lack of similar improvement in the placebo group. Additionally, biopsy responders with stage F3 fibrosis at baseline had similar or more pronounced improvements in HRQoL compared with responders with F2 or F1B fibrosis at baseline.^2,3

“At the end of the day, a patient doesn’t understand their fibrosis stage or their ELF score or their FibroScan score. They may or may not really get the variables that are important to clinicians,” Younossi explained. “They want to make sure that they feel better, and ultimately, they are not going to risk bad liver disease in the future. This answers the first piece, that if you respond to this treatment, you will also have some improvement in your quality of life.”

References

1. ^{Brooks, A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed October 8, 2024. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash}
2. ^{Madrigal Pharmaceuticals. Madrigal Pharmaceuticals Announces Publication of Positive Health-Related Quality of Life Results from the Phase 3 MAESTRO-NASH Trial of Rezdiffra™ (resmetirom). September 30, 2024. Accessed October 8, 2024. https://ir.madrigalpharma.com/news-releases/news-release-details/madrigal-pharmaceuticals-announces-publication-positive-health}
3. ^{Younossi ZM, Stepanova M, Racila A, et al. Health-Related quality of life (HRQL) assessments in a 52-Week, Double-Blind, randomized, Placebo-Controlled phase 3 study of resmetirom (MGL-3196) in patients with metabolic dysfunction associated steatohepatitis (MASH) and fibrosis. Hepatology. doi:10.1097/HEP.0000000000001084}