Integrated Insights, Clinical Connections: Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Leverage Integrated Data to Inform Better Benefit Decisions

An estimated 22 million U.S. adults are affected by a chronic liver condition called metabolic dysfunction-associated steatohepatitis (MASH). There were no medications specifically indicated for MASH treatment in individuals with moderate to advanced liver scarring until the FDA approval of Rezdiffra in April 2024, granted under the accelerated pathway. This treatment has an annual cost of $50,000 and can improve symptoms of liver disease as well as decrease liver scarring. While this treatment is a welcome clinical option for patients, it does create a need for payers to make complex decisions about utilization management and cost containment strategies for an existing condition among members where no treatment option was previously available. Understanding the clinical landscape, emerging treatment options, the current member population with MASH, and the potential impact on spend from new treatments is crucial for developing an effective benefit strategy that balances patient access with fiscal responsibility.

Clinical Pharmacist Highlight: MASH

MASH develops when excess fat accumulates in liver cells and was previously known as nonalcoholic fatty liver disease or nonalcoholic steatohepatitis (NASH). This accumulation triggers chronic inflammation that can progress to severe liver damage, potentially requiring liver transplantation or leading to liver cancer and death. Several conditions significantly increase MASH risk, including obesity, Type 2 diabetes, and high cholesterol. Current estimates suggest over 15% of U.S. adults may have MASH, with over 20% of patients at risk of developing cirrhosis.

The MASH treatment pipeline shows significant promise, with potential expanded indications of existing GLP-1 therapies as well as diverse novel therapies in development over the coming years, such as fibroblast growth factor 21 analogs like efruxifermin and pegozafermin, a new type of GLP-1 like survodutide, and VK2809, which is a thyroid hormone receptor agonist like Rezdiffra. Similar to other chronic conditions like hypertension and diabetes, MASH management may eventually require multiple medications to effectively treat liver disease.

Beyond pharmaceutical interventions, lifestyle modifications play a crucial role in MASH management. Key recommendations include achieving 3-10% body weight loss, engaging in regular physical activity, adopting a Mediterranean diet rich in healthy fats, vegetables, and whole grains, and avoiding alcohol and tobacco use. These lifestyle changes can significantly impact disease progression and treatment outcomes.

Why It Matters To Payers: Emerging Cost Driver

In April 2024, the FDA approved Rezdiffra (resmetirom) as the first medication specifically indicated for MASH treatment in individuals with moderate to advanced liver scarring. The approval came through the FDA’s accelerated approval pathway, designed to address serious conditions with significant unmet medical needs. Clinical trial results showed a meaningful ability to resolve MASH without worsening fibrosis, as well as improving fibrosis by at least one stage. Given the large population that could benefit from therapy, and only one available treatment on the market, healthcare providers welcomed Rezdiffra’s approval as a potential breakthrough treatment option. However, with an estimated annual cost of $50,000, the medication has prompted plan sponsors to implement utilization management strategies ensuring appropriate use and evidence of benefit for eligible patient populations.

Despite current utilization management approaches, including some coverage exclusions, Rezdiffra uptake continues to grow steadily. Industry projections estimate 2025 sales will approach $600 million. Increasing utilization, high cost, and a growing pipeline make MASH treatment a critical category for benefit strategy development and ongoing monitoring.

MASH Drug Benefit Considerations

Leveraging UM that prefers lower-cost, clinically effective alternatives from the upcoming pipeline medications with expanded indications for MASH treatment as well as novel therapies is a potential strategy for cost mitigation given the price tag of Rezdiffra. As expanded indications for selected GLP-1 therapies come to market, they provide an opportunity to treat patients in a way that is both clinically effective and has less overall cost to the plan. Both semaglutide and tirzepatide have undergone clinical studies for MASH treatment with promising results. Novo Nordisk has already submitted semaglutide to the FDA for the expanded indication, expecting FDA review Q4 2025. Research demonstrates that semaglutide, studied in both diabetic and non-diabetic MASH patients, achieves similar outcomes to Rezdiffra, reducing liver scarring and resolving liver inflammation.

The potential addition of new pipeline drugs to MASH treatment options may offer significant cost advantages. However, the cost picture is complicated by combination therapy needs. Since newer pipeline drugs and Rezdiffra may work through different mechanisms, approximately 25% of MASH patients may require two medications, increasing annual treatment costs. It is essential to have the right utilization management strategy to address and facilitate the layering of multiple therapies for MASH management, ensuring appropriate use and controlling plan costs without duplication of therapies.  This can be achieved with prior authorization and step therapy, as well as considering preferred therapies as the number of treatment options grows. Given the unmet medical need and affected population size, MASH treatment could easily become a top spending trend for plan sponsors in 2026 and 2027.

Integrated Data Highlight: MASH

Effective planning for MASH utilization and budget impact requires accurate identification of affected plan members. With historically limited treatment options, determining MASH population size has been challenging. Medical diagnosis codes from claims data can enhance identification efforts significantly.

Tools like Artemetrx, which leverage both medical and pharmacy data, simplify MASH population identification and enable more accurate cost projections. Integrated data assessment and analytics can identify individuals with MASH and highlight important subpopulations, such as those with concurrent Type 2 diabetes.

This comprehensive data approach allows plan sponsors to assess utilization patterns, evaluate additional therapy use like GLP-1s, and develop targeted utilization management strategies. The ability to analyze these patterns is essential for accurate cost projection and effective benefit design.

Inform Benefit Decisions, Enhance Member Outcomes

MASH represents a significant emerging challenge for healthcare payers, with treatment costs poised to become a major spend driver as new therapies gain approval and utilization increases. Leveraging integrated data analytics to identify at-risk populations, understand utilization patterns, and project costs will be crucial for developing effective cost management strategies that ensure appropriate patient access while controlling spend. To learn more about how integrated data solutions can help your organization navigate the evolving MASH treatment landscape, connect with our experts today.