VIDEO: FAST, Agile 3+ scores may predict treatment benefit in MASH, advanced fibrosis

Key takeaways:

• Agile 3+ correctly identified more patients at high risk for MASH (55% vs. 33%).
• FAST misclassified fewer patients as having low risk MASH among those with stage 2 and 3 fibrosis.

SAN DIEGO — Both FibroScan-aspartate aminotransferase and Agile 3+ scores “performed well” in predicting risk for advanced fibrosis in patients with metabolic dysfunction-associated steatohepatitis who had been treated with pegozafermin.

“There is an urgent need to develop noninvasive tests to hopefully replace biopsy in the future to select patients for promising treatments like pegozafermin,” Naim Alkhouri, MD, FAASLD, DABOM, chief medical officer of Arizona Liver Health, told Healio. “Two of these promising noninvasive tests, or NITs, are the FAST score, which stands for Fibroscan-AST, and then we also have the Agile 3+ score that includes FibroScan data and other clinical variables.”

To investigate the diagnostic potential of FAST and Agile 3+ in detecting “significant and advanced fibrosis,” Alkhouri and colleagues examined data from the phase 2b ENLIVEN trial of 192 patients (mean age, 56 years; 61% women) with MASH and stage 2 (n = 65) or 3 (n = 127) fibrosis who were randomly assigned to pegozafermin or placebo.

At baseline, the researchers performed FibroScan to determine FAST and Agile 3+ scores. Using established cut-off scores for FAST and Agile 3+ for, researchers determined the scores’ ability to correctly risk stratify patients as rule-out (low-risk MASH), indeterminate (moderate-risk MASH) or rule-in (high-risk MASH).

Results demonstrated that the Agile 3+ score correctly identified more patients with high risk for MASH (55% vs. 33%) while the FAST score misclassified fewer patients as having low risk for MASH among those with stage 2 (29% vs. 46%) or stage 3 (17% vs. 22%) fibrosis.

“Both [FAST and Agile 3+] performed well in selecting patients that may benefit from pegozafermin and other therapeutics,” Alkhouri said. “Hopefully, in the future, these [NIT scores] will be also routinely implemented in our clinical practices to select patients for treatment and monitor them. This is very important because we know that MASH is underdiagnosed and undertreated and it could be a progressive disease that can lead to the development of cirrhosis and its complications.”

References:

• Alkhouri N, et al. Biomarker response in metabolic dysfunction-associated steatohepatitis (MASH) patients with high-risk baseline FAST scores: Observations from the ENLIVEN Phase2b trial with pegozafermin. Presented at: The Liver Meeting; Nov. 15-19, 2024; San Diego (hybrid meeting).
• Alkhouri N, et al. Diagnostic potential of FAST and AGILE3+ scores for F2/F3 fibrosis: An analysis of the phase 2 ENLIVEN study. Presented at: The Liver Meeting; Nov. 15-19, 2024; San Diego (hybrid meeting).