Early experience with resmetirom to treat metabolic dysfunction-associated steatohepatitis with fibrosis in a real-world setting

Abstract

Background: Resmetirom was conditionally approved in the United States recently for treating metabolic dysfunction-associated steatohepatitis with stage 2 and 3 fibrosis. However, its availability to patients requires preauthorization by the payors and is dispensed only through selected specialty pharmacies.

Methods: We established a multistakeholder and multistep resmetirom prescription process pivoting to a dedicated pharmacist. It incorporates liver biochemistry testing at 12 weeks and liver clinic follow-up at 6 months after starting resmetirom.

Results: Fifteen hepatology providers prescribed resmetirom to 113 patients from April 1, 2024, to November 8, 2024, with histologic eligibility in 70% and noninvasive criteria in 30%. Resmetirom treatment was approved for 110 patients (97%), including 8 patients receiving the pharmaceutical company's patient assistance and 6 patients receiving bridge support to cover the co-pay. Eighty-three patients initiated resmetirom at an average of 30 days after its prescription. Adverse events were reported by 41% of patients taking resmetirom, and they were predominantly related to gastrointestinal symptoms and pruritus and/or rash with no evidence of hypersensitivity. Thirteen patients (16%) discontinued resmetirom after an average of 25.5 days (range: 2-68 d), with 11 patients discontinuing due to adverse events. The adverse events leading to discontinuation were nausea, diarrhea, and vomiting (n=4), right upper quadrant discomfort (n=2), left lower quadrant pain (n=1), rash with pruritus (n=1), pruritus and rash with indirect hyperbilirubinemia (n=1), dizziness (n=1), and mental fogginess (n=1). Follow-up liver biochemistries available in 24 patients showed no evidence of DILI.

Conclusions: Our prescription pathway effectively dispensed resmetirom to nearly all patients who were prescribed resmetirom. One in 6 patients discontinued resmetirom, primarily due to side effects. This high discontinuation rate may be mitigated by modifying our follow-up from "prescribe and forget" to "prescribe and closely follow."

Keywords: DILI; LSM; MASH; VCTE; adverse events; fibrosis; resmetirom; side effects.

Graphical abstract

FIGURE 1

Resmetirom prescribing pathway at Indiana University Health Academic Health Center. This figure outlines the multistep and multistakeholder process for a patient to receive resmetirom and a clinical follow-up schedule after starting to take the medication.

FIGURE 2

Approach to appeal the denial by payors and a description of Madrigal’s Patient Assistance Program. This figure outlines the steps needed for a patient to receive resmetirom if prior authorizations have been denied by the payor. The manufacturer evaluates on a case-by-case basis to provide the medication at a low or free cost to patients. The manufacturer requires 2 appeal denials for the long-term bridge. *Long-term bridge requires 2 appeal denials.

FIGURE 3

Disposition of 113 patients who were prescribed resmetirom between April 2024 and November 2024. This flowchart describes the number of patients who were initially referred and approved for resmetirom. Of 110 patients receiving approval, 83 reported starting resmetirom while 25 did not. Of 83 who started resmetirom, 70 remained on the regimen while 13 discontinued. *Approved by Payor or Madrigal Patient Assistance Program.

FIGURE 4

Changes in liver biochemistries among patients who continued resmetirom therapy. (A) Changes in ALT after starting resmetirom. (B) Changes in ALP after starting resmetirom. (C) Changes in serum total bilirubin after starting resmetirom.