From the Guidelines
Resmetirom is a thyroid hormone receptor beta agonist medication that has been approved by the FDA for treating non-alcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis, and its use should be prioritized in patients with at-risk MASH, defined as those with significant fibrosis and at least 3 cardiometabolic risk factors, as recommended by the EASL-EASD-EASO clinical practice guidelines 1.
Key Points
- The standard dosage of resmetirom is 80 mg taken orally once daily, with the option to increase to 100 mg if needed and tolerated, based on the FDA label and expert panel recommendations 1.
- Resmetirom works by selectively activating thyroid hormone receptor beta in the liver, which helps reduce liver fat, inflammation, and fibrosis while avoiding the cardiac and bone side effects associated with broader thyroid hormone activation, as demonstrated in the MAESTRO-NASH trial 1.
- Common side effects include diarrhea, nausea, abdominal pain, and constipation, and patients should take resmetirom with food to improve absorption and reduce gastrointestinal side effects, as recommended by the FDA label and expert panel recommendations 1.
- Regular monitoring of liver function tests is recommended during treatment, and the assessment of response to resmetirom should be broken into 3 periods: initial assessment for safety and tolerability at 12 weeks, assessment at 6 months for disease monitoring, and assessment at 12 months and annually for efficacy monitoring, as recommended by expert panel recommendations 1.
- Resmetirom is not recommended for patients with decompensated cirrhosis or those with hyperthyroidism, and its use should be cautious in patients with advanced cirrhosis, as recommended by the EASL-EASD-EASO clinical practice guidelines 1 and expert panel recommendations 1.
Non-Invasive Tests (NITs)
- NITs, such as VCTE, MRI-PDFF, and ELF, can be used to identify patients with at-risk MASH and to monitor treatment response, but their use should be guided by expert panel recommendations and clinical practice guidelines 1.
- The choice of NITs and settings of assessment may be further optimized, particularly in the setting of general population-based screening and/or specific sub-groups, as recommended by the EASL-EASD-EASO clinical practice guidelines 1.
Treatment Failure
- Treatment failure should be defined as worsening values on VCTE (>30%), liver enzymes (>20%), and/or MRI-PDFF (<30% relative to baseline improvement), and patients with treatment failure should be considered for other strategies, such as switching to another medication or repeat liver biopsy, as recommended by expert panel recommendations 1.
Other Considerations
- Resmetirom is a CYP2C8, OATP1B1, and OATPB1B3 substrate, and its concomitant use with strong CYP2C8 inhibitors or OATP1B1 and OATPB1B3 substrates is not recommended, as recommended by the FDA label and expert panel recommendations 1.
- The use of resmetirom with moderate CYP2C8 inhibitors can be considered after dosage reduction of resmetirom and should trigger closer safety monitoring, as recommended by expert panel recommendations 1.
From the FDA Drug Label
REZDIFFRA is a prescribed medicine used along with diet and exercise to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver.
The use of Resmetirom (Metyrapone) is for the treatment of adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver, in combination with diet and exercise 2.
- The primary goal of treatment is to achieve resolution of steatohepatitis without worsening of fibrosis and one stage improvement in fibrosis without worsening of steatohepatitis.
- Key points to consider when using Resmetirom include:
- Liver injury (hepatotoxicity) is a potential side effect, and patients should be monitored for signs and symptoms of hepatotoxicity.
- Gallbladder problems can occur with NASH and may occur if you take Resmetirom.
- Resmetirom may interact with other medicines, including gemfibrozil, cyclosporine, clopidogrel, and statin medicines.
- Patients should inform their healthcare provider about all medical conditions, including liver problems, gallbladder problems, pregnancy, and breastfeeding.
From the Research
Use of Resmetirom (Metyrapone)
- Resmetirom is a liver-directed, thyroid hormone receptor beta-selective agonist used for the treatment of nonalcoholic steatohepatitis (NASH) 3, 4, 5, 6, 7.
- The medication has been shown to improve hepatic fat content, liver enzymes, and fibrosis biomarkers in NASH patients 5, 6, 7.
- Resmetirom has been found to achieve greater reductions from baseline in hepatic fat content assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF) compared to placebo 4, 5, 7.
- The drug has also been shown to improve NASH resolution and ≥2-point nonalcoholic fatty liver disease activity score reduction 5.
- Resmetirom is generally well-tolerated, with common adverse events including nausea and diarrhea 3, 4, 5, 6, 7.
Efficacy of Resmetirom
- Resmetirom has been found to be effective in improving fibrosis risk ratios, reducing liver fat content, and enhancing liver fibrosis score compared to placebo 6.
- The medication has also been shown to improve levels of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT) 7.
- Resmetirom has been found to reduce low-density lipoprotein (LDL) and triglyceride (TG) levels, as well as reverse triiodothyronine (rT3) levels 5, 7.
Safety of Resmetirom
- Resmetirom has been found to be associated with a higher likelihood of experiencing diarrhea and nausea compared to placebo 4, 5, 6, 7.
- However, the medication has not been found to be associated with a significant increase in the risk of urinary tract infection (UTI) or headaches 7.
- Resmetirom has been found to be well-tolerated, with most adverse events being mild or moderate 3, 4, 5, 6, 7.