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Questions and Answers
What is the significance of resmetirom at doses of 80 mg and 100 mg?
What is the significance of resmetirom at doses of 80 mg and 100 mg?
What is the estimated global prevalence of NAFLD?
What is the estimated global prevalence of NAFLD?
Which of the following is a condition commonly associated with NASH?
Which of the following is a condition commonly associated with NASH?
What diagnostic method is currently needed to confirm NASH?
What diagnostic method is currently needed to confirm NASH?
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What percentage of patients with NAFLD are estimated to have NASH?
What percentage of patients with NAFLD are estimated to have NASH?
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Which of the following is NOT a potential complication of NAFLD?
Which of the following is NOT a potential complication of NAFLD?
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Which of the following statements about the safety profile of resmetirom is true?
Which of the following statements about the safety profile of resmetirom is true?
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Which of the following conditions can lead to the progression of NAFLD?
Which of the following conditions can lead to the progression of NAFLD?
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What was the percentage increase of ALT to ≥3 × ULN in the placebo arm compared to the resmetirom arms?
What was the percentage increase of ALT to ≥3 × ULN in the placebo arm compared to the resmetirom arms?
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What was the P-value indicating the significance of the treatment difference at week 52 between resmetirom and placebo?
What was the P-value indicating the significance of the treatment difference at week 52 between resmetirom and placebo?
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Which ELF score baseline indicates a subset of patients evaluated for the resmetirom treatment efficacy?
Which ELF score baseline indicates a subset of patients evaluated for the resmetirom treatment efficacy?
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In the study, the levels of reverse triiodothyronine were noted to be reduced in which treatment group?
In the study, the levels of reverse triiodothyronine were noted to be reduced in which treatment group?
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What was observed regarding liver enzymes in the resmetirom arms?
What was observed regarding liver enzymes in the resmetirom arms?
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What percentage reduction in LDL-C was observed with 100 mg of resmetirom treatment at week 24?
What percentage reduction in LDL-C was observed with 100 mg of resmetirom treatment at week 24?
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What was the defined SHBG response that corresponded to the upper two tertiles?
What was the defined SHBG response that corresponded to the upper two tertiles?
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Which lipid parameter showed the greatest reduction at the 80 mg dosage of resmetirom?
Which lipid parameter showed the greatest reduction at the 80 mg dosage of resmetirom?
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What was the percentage of patients reporting abdominal pain at the onset of ≤12 weeks?
What was the percentage of patients reporting abdominal pain at the onset of ≤12 weeks?
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Which adverse effect had the highest percentage in the reported data?
Which adverse effect had the highest percentage in the reported data?
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What was the percentage reduction in apoB for patients with LDL-C ≥ 100 mg dl−1 treated with 100 mg of resmetirom?
What was the percentage reduction in apoB for patients with LDL-C ≥ 100 mg dl−1 treated with 100 mg of resmetirom?
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What percentage of patients reported nausea with resmetirom treatment at 80 mg?
What percentage of patients reported nausea with resmetirom treatment at 80 mg?
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How was the lower exposure to resmetirom defined in the study?
How was the lower exposure to resmetirom defined in the study?
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What was the primary end point of the MAESTRO-NAFLD-1 trial?
What was the primary end point of the MAESTRO-NAFLD-1 trial?
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How many patients were screened for the MAESTRO-NAFLD-1 trial?
How many patients were screened for the MAESTRO-NAFLD-1 trial?
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What percentage of patients receiving resmetirom reported a TEAE during the trial?
What percentage of patients receiving resmetirom reported a TEAE during the trial?
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Which of the following statements about the patient disposition in the trial is true?
Which of the following statements about the patient disposition in the trial is true?
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During the trial, how many serious TEAEs were reported?
During the trial, how many serious TEAEs were reported?
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What was the randomization distribution for the DB arms in the trial?
What was the randomization distribution for the DB arms in the trial?
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What were the majority of TEAEs in the study characterized as?
What were the majority of TEAEs in the study characterized as?
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What proportion of serious TEAEs were related to COVID-19 pneumonia or diagnosis during the trial?
What proportion of serious TEAEs were related to COVID-19 pneumonia or diagnosis during the trial?
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What was the significant percentage reduction in low-density lipoprotein cholesterol (LDL-C) at the 100 mg resmetirom treatment compared to placebo?
What was the significant percentage reduction in low-density lipoprotein cholesterol (LDL-C) at the 100 mg resmetirom treatment compared to placebo?
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Which of the following was the least squares mean relative reduction in triglycerides (TGs) at the 80 mg resmetirom treatment compared to baseline?
Which of the following was the least squares mean relative reduction in triglycerides (TGs) at the 80 mg resmetirom treatment compared to baseline?
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What was the percentage change in hepatic fat at week 52 in the OL 100 mg resmetirom arm?
What was the percentage change in hepatic fat at week 52 in the OL 100 mg resmetirom arm?
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Which treatment showed a significant reduction in apolipoprotein B (apoB) at 80 mg compared to baseline?
Which treatment showed a significant reduction in apolipoprotein B (apoB) at 80 mg compared to baseline?
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What was the significant reduction in triglycerides (TGs) observed from baseline for the 100 mg resmetirom arm at week 24?
What was the significant reduction in triglycerides (TGs) observed from baseline for the 100 mg resmetirom arm at week 24?
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How did the effects of the resmetirom treatment at week 24 compare to the placebo effect?
How did the effects of the resmetirom treatment at week 24 compare to the placebo effect?
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At what dose did the resmetirom treatment achieve a reduction in low-density lipoprotein cholesterol (LDL-C) of −12.4%?
At what dose did the resmetirom treatment achieve a reduction in low-density lipoprotein cholesterol (LDL-C) of −12.4%?
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What underlying issue was noted that could have impacted treatment adherence in the double-blind arms?
What underlying issue was noted that could have impacted treatment adherence in the double-blind arms?
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What was the percentage of patients who achieved a ≥2 kPa reduction from baseline in the resmetirom arms compared to the placebo arm?
What was the percentage of patients who achieved a ≥2 kPa reduction from baseline in the resmetirom arms compared to the placebo arm?
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What effect did resmetirom treatment have on ALT, AST, and GGT levels in patients with baseline ALT ≥ 30 IU l−1?
What effect did resmetirom treatment have on ALT, AST, and GGT levels in patients with baseline ALT ≥ 30 IU l−1?
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What was the baseline liver stiffness measurement (LSM) threshold criteria used for analysis?
What was the baseline liver stiffness measurement (LSM) threshold criteria used for analysis?
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At week 52, how did the mean change from baseline in VCTE compare between the resmetirom and placebo arms?
At week 52, how did the mean change from baseline in VCTE compare between the resmetirom and placebo arms?
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What correlation was observed with SHBG levels during the treatment period?
What correlation was observed with SHBG levels during the treatment period?
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What does an increase in SHBG reflect in relation to resmetirom treatment?
What does an increase in SHBG reflect in relation to resmetirom treatment?
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What was the mean baseline alanine aminotransferase (ALT) level in the studied population?
What was the mean baseline alanine aminotransferase (ALT) level in the studied population?
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What was the outcome for patients in the OL 100 mg and DB 100 mg resmetirom arms at week 52 compared to placebo?
What was the outcome for patients in the OL 100 mg and DB 100 mg resmetirom arms at week 52 compared to placebo?
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Study Notes
Resmetirom for Nonalcoholic Fatty Liver Disease
- Nonalcoholic steatohepatitis (NASH) is a progressive liver disease without approved treatment
- MAESTRO-NAFLD-1 was a 52-week, randomized, double-blind, placebo-controlled phase 3 trial examining resmetirom's safety in adults with presumed NASH
- Participants were randomly assigned to three groups: 100 mg resmetirom, 80 mg resmetirom, or placebo, and another group received 100 mg resmetirom in an open-label fashion.
- The primary outcome was the incidence of treatment-emergent adverse events (TEAEs) over 52 weeks. Secondary outcomes included LDL-C, apoB, triglycerides (over 24 weeks), hepatic fat (over 16 and 52 weeks), and liver stiffness (over 52 weeks)
- Resmetirom was safe and well-tolerated, TEAEs occurred in 86.5% (open-label 100 mg group), 86.1% (100 mg group), 88.4% (80 mg group), and 81.8% (placebo) of patients. TEAEs above placebo included diarrhea and nausea during treatment initiation.
- Key secondary outcomes showed significant improvements in LDL-C (11.1%-12.6% lower, compared to placebo), apoB (-15.6% to -18%), triglycerides (-15.4% to -20.4%), hepatic fat (better reduction at 16 weeks and at 52 weeks), and liver stiffness, in higher resmetirom doses compared to placebo.
Patient Disposition
- 1,988 patients were screened, 1143 were randomized
- 972 to three double-blind treatment arms (100mg resmetirom, 80mg resmetirom, placebo); 171 were in the open-label 100 mg group.
- 969 patients in the double-blind arms completed the study; 152 from the open label completed..
- The COVID-19 pandemic impacted some study drug deliveries and patient visits (missed study visits in DB arms were 86-88%).
Secondary Outcomes
- Lipid Panel Improvements: Resmetirom significantly reduced LDL-C, apoB, triglycerides, and other atherogenic lipid markers at week 24 and 48 compared to placebo
- Hepatic Fat Reductions: Resmetirom reduced hepatic fat, as measured by MRI-PDFF, significantly at both 16 and 52 weeks
- Liver Stiffness: While showing a promising trend, significant changes in liver stiffness (as measured by FibroScan or MRE) weren't found compared to placebo at week 52.
Liver Injury Biomarkers
- Liver injury biomarkers (ALT, AST, GGT) showed statistically significant improvements from baseline following resmetirom treatment in patients with elevated baseline ALT.
- Increased SHBG levels were associated with greater hepatic fat reduction.
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Description
Explore the findings of the MAESTRO-NAFLD-1 trial on resmetirom for treating nonalcoholic fatty liver disease (NASH). This quiz covers the safety data, treatment-emergent adverse events, and key secondary outcomes related to LDL-C and liver stiffness. Test your knowledge on this important study in liver disease management.
