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.

Two weeks ago, the SurfingMASH Question of the Week asked, "What structural or educational changes do you anticipate will significantly improve Provider-Patient communication? Will these changes require more from the provider and more from the patient?" Today, S5 E23 panelists Mike Betel and José Willemse join Roger Green to review the three answers we received.

Of the three questions from audience members, one from a patient/patient advocate suggested greater honesty, better listening, and, if possible, either longer appointments or better care team engagement. The second, from another patient, discussed being more honest about the Quality of Life impact of immunological drugs, along with ways to manage these drugs better. The third, from a public health official in Argentina, discussed increasing the use of multidisciplinary teams to educate and empower individuals around healthy habits and lifestyles.

To Mike, these answers all convey the need for "tailored care," a care and engagement process suited to each patient's individual situation in terms of disease(s) and quality of life needs and issues. He also suggests that pharmaceutical companies help educate physicians on these issues while discussing the disease and use of their medicines.

José notes that it might not be possible to get more time for a visit, but the physician could improve the visit immensely by asking patients true open-ended questions about their feelings and concerns and then actively listening to their answers. She also suggests that physicians not act like they are time-compressed. If physicians act more leisurely, patients will be more comfortable, even if they do not take up more time.

Roger suggests that the format of physician protocols and instructions might be part of the problem. If the physicians are evaluated by their employers based on their ability to work through an entire checklist in 15 minutes, they will focus first on the clock and second on the checklist. This will not leave time for patient questions and, even worse, will leave the patient afraid to take up any more of the physician's time than is necessary. Thus no true communication develops.

Mike goes back to a point that José made during the original episode: physicians should close their computer screens and look at the patients. Roger goes back to the question about immunosuppressants to ask whether providers can assess patients' abilities to manage medications that cause or exacerbate depression and then offer advice and perhaps antidepressants as appropriate.

Given all these emotive patient needs, José suggests that patient support groups have tremendous value, and Roger notes the presence of online support structures like HOPE from Sober Livers (Season 5 Episode 18). After asking where to find resources for these kinds of activities (particularly in less wealthy parts of the world), the conversation ends.

In the second half of Roger Green's interview with Global Liver Institute Vice President, Liver Programs Jeff McIntyre, Jeff discusses the implications of his key EASL Congress takeaways for GLI and other patient advocacy groups.

To Jeff, this trend makes patient advocates a more valuable player in the clinical trial design process, particularly when coupled with the FDA's increasing focus on diversity in trial populations. This will become particularly important because, today, the major use of incretin agonists like semaglutide and tirzepatide is in anti-obesity, where payers are frequently declining to pay for the drugs. Advocates like GLI will be pivotal in ensuring that patients who need MASLD drugs will still get the drugs they need, particularly at earlier stages of fibrosis. This discrimination may allow patients to receive incretin agonists during the pre-fibrosis stage based on diabetes and anti-obesity medications and reserve the fibrosis drugs for patients with more advanced MASH. The entire scenario of early metabolic, later MASH treatment with different agents is at least 4-5 years in the future. In the meantime, Jeff sees a need to advocate for underserved groups in the population while at the same time laying the foundation for the longer-term case. In this context, the United Nations General Assembly side effect (covered in S5, E22) is an exciting and vital event.