S5 - E25 - Reviewing Expert Recommendations on the Use of Resmetirom

00:00:00 - Surf's Up: Season 5 Episode 25
On July 20, Clinical Gastroenterology and Hepatology released the paper, Expert Panel Recommendations: Practical Clinical Applications for Initiating and Monitoring Resmetirom in Patients with MASH/NASH and Moderate to non-cirrhotic Advanced Fibrosis. Corresponding author Maru Rinella joins the Surfers to share key points from the recommendations and offer her thoughts on what lay behind them.

00:02:26 - Introduction and Groundbreaker
The highlight was Louise's groundbreaker: having become a full Fellow in the Roal College of Physicians.

00:06:28 - Introducing the paper
Roger starts by discussing the importance of this paper and listing the questions the panel will address during the episode. Maru provides a history of developing the paper. Jörn praises its timeliness. 

00:08:59 - Treating the "Right" patients; Using the "Right" tests
Jörh asks why the authors changed the patient definition from a histological one to at-risk MASH patients confirmed by NITs. Maru said the authors sought to follow the FDA guidance on NITs and patient targets. They considered adding liver enzymes or confirmatory VCTE to the protocol, but demurred because not every clinical could execute such a recommendation. 

Jörn asks whether the authors considered requiring three metabolic risk factors. Roger notes that this question implies a need to prioritize patients, which is a factor in Europe but not the U.S. This paper takes a more U.S-based perspective, which is to set a threshold for use.  

00:14:21 - The Decision Not to Discuss Cost
The authors did not address costs because they anticipated steep reductions over time. The panel compares the MASH case to HCV. In HCV, the combination of high drug costs and large number of warehoused patients drove prioritization over time. 

00:16:34 - Relative paucity of warehoused MASH patients 
Maru suggests relatively few MASH patients are warehoused. Louise asks whether many U.S. insurers are controlling access by requiring liver biopsy. Maru reports she has not encountered this personally and  estimates it might affect ~5% of cases so far. 

00:19:05 - Rationale for Patient Selection
Maru explains the rationale for an F2 threshold for patient selection: patients with fibrosis >= F2 show a demonstrable decline in long-term survival. The rationale for excluding cirrhosis patients? Resmetirom is not yet proven to help patients with cirrhosis. Jörn notes, the MAESTRO-OUTCOMES trial is running and will generate consequential data on cirrhosis. 

00:22:11 - Value of Stabilizing Disease without Improvement
Maru notes that the paper focused strongly on how to stabilize patients because the drug is safe and stabilization has real-world benefits.. She points out that patient advocates strongly recommend this focus. All this led to the paper's recommendation to discontinue only upon progression.  

00:25:12 - The importance of incremental learning
The group agrees that these recommendations comprise a base that will be strengthened over time as individual providers gain experience with the drug. 

00:30:06 - Wrapping up
Panelists touch briefly on the value of loose discontinuation rules, how patients feel about starting therapy, how to handle drug interactions, and how the paper is used in the US vs. other countries. In closing, the group remembers Stephen Harrison's unique contributions one more time.

00:37:55 - Question of the Week
Which of the paper's two striking recommendations -- using multiple NITs to qualify patients and continuing therapy unless and until a patient shows signs of disease progression -- will have greater impact on how physicians treat patients?

00:38:44 - Business Report
Summer schedules, value of the business report, the vault discussion.