Resmetirom proves efficacy in NASH patients with or without MetALD

Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and fibrosis treated with resmetirom achieve NASH resolution with no fibrosis worsening (NR) or ≥1-stage fibrosis improvement with no worsening of the NAS score (FI), according to the results of the ongoing MAESTRO-NASH study.

In a subgroup analysis, similar response rates have been noted between those with suspected metabolic dysfunction-associated and alcohol-associated liver disease (MetALD) and without MetALD.

“A total of 75 (9.6 percent) patients had possible MetALD during the first 52 weeks of MAESTRO-NASH,” said lead investigator Dr Vlad Ratziu, Sorbonne Universite, Institute for Cardiometabolism and Nutrition, APHP, Centre de Recherche des Cordeliers, Paris, France.

“Baseline characteristics showed a higher mean gamma-glutamyl transpeptidase (GGT) and Fibrosis-4 (FIB-4) [score] in the MetALD versus low alcohol group,” he added.

In this ongoing trial, Ratziu and his team longitudinally collected the carbohydrate deficient transferrin (CDT) in patients over 52 weeks. They also conducted a PEth test following randomization in those suspected of increased alcohol consumption.

Participants with baseline or postbaseline CDT >2.5 percent (ULN 2.47) and/or a PEth >20 ng/ml (ULN 20 ng/ml) were assigned to a possible MetALD subgroup. The investigators then analysed the 782 patients who had both a baseline and week 52 biopsy.

Response rates

Of the analysed patients, 75 (9.6 percent) had MetALD and were assigned to a subgroup; the remaining 707 had no MetALD. Baseline characteristics did not significantly differ between the MetALD and nonalcohol subgroups. [EASL 2024, abstract SAT-263]

In the subgroup of patients with low or no alcoholic consumption, 224 received resmetirom 80 mg and 228 received the 100-mg dose. Of those treated with resmetirom, 29.9 percent and 36 percent had NR, 29 percent and 33.3 percent had FI, and 59.2 percent and 71.2 percent showed a ≥30-percent decrease in MRI-PDFF from baseline, respectively.

The corresponding rates for patients treated with placebo (n=255) were 10.3 percent, 13.7 percent, and 24.5 percent.

In the MetALD subgroup, 34 patients received resmetirom 80 mg and 20 received the 100-mg dose. Of the resmetirom-treated individuals, 29 percent and 35 percent had NR, 35 percent and 30 percent had FI, and 88 percent and 81 percent had a ≥30-percent reduction in MRI-PDFF from baseline, respectively. The corresponding results for those on placebo (n=21) were 10 percent, 19 percent, and 14 percent.

“Response rates to resmetirom in patients with suspected MetALD were similar to those without MetALD,” Ratziu said.

Quality of life

In a separate analysis of the MAESTRO-NASH study, NASH patients who achieved fibrosis improvement or NASH resolution with resmetirom also experienced improvements in health-related quality of life (HRQOL) at week 52. [EASL 2024, abstract FRI-202]

MAESTRO-NASH is a 54-month, randomized, double-blind, placebo-controlled phase III trial evaluating the efficacy of resmetirom in patients with biopsy-confirmed NASH and fibrosis. A total of 966 patients were randomly assigned to receive resmetirom 80 mg, resmetirom 100 mg, or placebo once daily.

NASH, also known as metabolic dysfunction-associated steatohepatitis, is a highly prevalent liver disease that can lead to adverse clinical outcomes and worsen HRQOL.