What percentage of adult patients with a history of metabolic disorders, such as non-alcoholic steatohepatitis (NASH), obesity, or metabolic syndrome, experience nausea or gastrointestinal side effects when taking Resmetirom (generic name), and what percentage of those patients have their symptoms significantly reduced with continued use?

Gastrointestinal Side Effects with Resmetirom

While the FDA label does not provide exact percentages of patients experiencing nausea or gastrointestinal side effects, the exposure-adjusted incidence rates show nausea occurs in 18 per 100 person-years for the 80 mg dose and 15 per 100 person-years for the 100 mg dose, with symptoms typically resolving within 26-28 days of continued use. 1

Incidence of Gastrointestinal Side Effects

The gastrointestinal adverse reactions with resmetirom are dose-dependent and occur early in treatment:

• Diarrhea has exposure-adjusted incidence rates of 23 per 100 person-years (80 mg dose) and 33 per 100 person-years (100 mg dose), compared to 14 per 100 person-years with placebo 1
• Nausea has exposure-adjusted incidence rates of 18 per 100 person-years (80 mg dose) and 15 per 100 person-years (100 mg dose), compared to 9 per 100 person-years with placebo 1
• Vomiting occurs at 7 per 100 person-years (80 mg) and 8 per 100 person-years (100 mg) 1
• Constipation occurs at 5 per 100 person-years (80 mg) and 8 per 100 person-years (100 mg) 1
• Abdominal pain occurs at 5 per 100 person-years (80 mg) and 7 per 100 person-years (100 mg) 1

In real-world clinical practice, 41% of patients reported adverse events, predominantly gastrointestinal symptoms and pruritus 2

Timeline and Resolution of Symptoms

Nausea

• Onset timing is dose-dependent: median time to onset is 28 days for the 80 mg dose versus 5 days for the 100 mg dose 3
• Duration: Mean duration is 26 days (80 mg dose) and 28 days (100 mg dose) 3
• Severity: Nausea is mild to moderate in severity 1

Diarrhea

• Onset timing: Median time to onset is 17 days (80 mg dose) and 6 days (100 mg dose) 3
• Duration: Median duration is 20 days for both dose groups 3
• Severity: Diarrhea is typically mild to moderate 1

Treatment Discontinuation Rates

Diarrhea and nausea led to treatment discontinuation in 8 per 100 person-years in the high-dose (100 mg) group 3

In real-world experience, 16% of patients discontinued resmetirom after an average of 25.5 days, with 11 of 13 discontinuations due to adverse events including nausea, diarrhea, and vomiting 2

Clinical Management Recommendations

Patient Education Strategy

Education of patients on potential gastrointestinal disorders is recommended to avoid unnecessary treatment discontinuations and increase treatment persistence rates in real-world settings 3

Key counseling points include:

• Gastrointestinal symptoms are expected early in treatment and are typically self-limited 3
• Symptoms generally resolve within 20-28 days with continued use 3
• The symptoms are mild to moderate in severity 1

Monitoring Timeline

• Week 12 assessment: Reserved to confirm absence of drug-induced liver injury, not for efficacy assessment 3
• 6-month assessment: Disease monitoring with consideration to discontinue if gastrointestinal symptoms are debilitating 3
• 12-month assessment: Full efficacy evaluation 3

Important Clinical Pitfalls

Do not discontinue treatment before Week 12 based solely on gastrointestinal symptoms unless they are debilitating, as these symptoms are expected to resolve with continued use 3

The high discontinuation rate observed in real-world practice (16%) may be mitigated by modifying the approach from "prescribe and forget" to "prescribe and closely follow" 2

The overall gastrointestinal adverse reaction rates were 73 per 100 person-years (80 mg dose) and 89 per 100 person-years (100 mg dose), compared to 57 per 100 person-years with placebo 1