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."