Mazen Noureddin, MD, MHSc: Starting, Monitoring Treatment with Resmetirom

March 14, 2024, was a historic day for the field of hepatology with the US Food and Drug Administration (FDA) approval of the first treatment for metabolic dysfunction-associated steatohepatitis (MASH), resmetirom (Rezdiffra). Less than a month later, it became available in US pharmacies, confirming the dawn of a new era of MASH management.^1,2

Although resmetirom’s conditional FDA approval and prompt availability in pharmacies presents a novel, long-awaited therapeutic for the progressive liver disease, significant challenges remain, including how to leverage noninvasive tests to identify patients with fibrosis stages 2-3 who should be treated with resmetirom, how to exclude patients with more advanced disease in whom resmetirom should not yet be used, and when to stop treatment.^1,3

“Clinicians were calling us asking ‘How do I start treatment? How do I monitor it?’ and we felt that we had to fill that gap really quickly,” Mazen Noureddin, MD, MHSc, a transplant hepatologist at Houston Methodist and director of the Houston Research Institute, said to HCPLive, explaining how he and a group of MASH experts felt the need to provide a consensus on the identification of at-risk MASH patients who may benefit from initiating treatment with resmetirom and recommendations for the assessment of treatment response, especially since the FDA “opened the door for NITs” by not requiring liver biopsy.³

Although Noureddin was careful to emphasize some of the finer details included in the expert panel recommendations and urged clinicians to read the full expert panel recommendation, he outlined what he believes to be some of the most important points from the paper, summarizing its contents as classifying which patients should and should not be treated with resmetirom. Specifically, he highlighted the need to confirm the diagnosis of MASLD, ensure the patient doesn’t have other liver diseases, and identify significant advanced fibrosis, either on liver biopsy or NITs, also emphasizing that patients with cirrhosis and portal hypertension should not be treated with resmetirom.

“We need more data on response to therapy,” Noureddin added, describing the need to exercise caution when using ALT and transient elastography to assess treatment response because some patients in MAESTRO NASH had improvement in histology but not on transient elastography and ALT. “You maybe have to use a combination, or even go back to the MRI PDFF if you have it and see if that 30% because it was the most predictive biomarker for response to therapy.”

Although GLP-1s are being studied for the treatment of MASH, Noureddin noted this class of medications is not yet approved for this indication and some GLP-1s lack clinical trial data proving their effect on fibrosis. “They're very promising, but they are not alternative [to resmetirom] at this point.

Editors’ note: Noureddin has relevant disclosures with Madrigal, Merck, Novo Nordisk, Takeda, Gilead, and others.

References

1. ^{Brooks, A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed August 5, 2024. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash}
2. ^{Brooks, A. Resmetirom (Rezdiffra) Now Available in US Pharmacies, Marks Turning Point in NASH Management. HCPLive. April 9, 2024. Accessed August 5, 2024. https://www.hcplive.com/view/resmetirom-rezdiffra-now-available-in-the-us-pharmacies-marks-turning-point-in-nash-management}
3. ^{Brooks, A. Considerations for Resmetirom Use, Monitoring in Patients with MASH, Fibrosis. HCPLive. August 5, 2024. Accessed August 5, 2024. https://www.hcplive.com/view/considerations-resmetirom-use-monitoring-patients-mash-fibrosis}