Resmetirom and Nonalcoholic Fatty Liver Disease
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Questions and Answers

What is the significance of resmetirom at doses of 80 mg and 100 mg?

  • It showed an increase in liver stiffness.
  • It was harmful and caused severe side effects.
  • It had no effect on hepatic fat or liver stiffness.
  • It resulted in significant reductions in LDL-C and triglycerides. (correct)

What is the estimated global prevalence of NAFLD?

  • Approximately 10%
  • Approximately 75%
  • Approximately 50%
  • Approximately 25% (correct)

Which of the following is a condition commonly associated with NASH?

  • Hyperthyroidism
  • Chronic obstructive pulmonary disease
  • Type 2 diabetes (correct)
  • Hypertension

What diagnostic method is currently needed to confirm NASH?

<p>Liver biopsy (D)</p> Signup and view all the answers

What percentage of patients with NAFLD are estimated to have NASH?

<p>25% (D)</p> Signup and view all the answers

Which of the following is NOT a potential complication of NAFLD?

<p>Asthma (C)</p> Signup and view all the answers

Which of the following statements about the safety profile of resmetirom is true?

<p>It was found to be safe and well tolerated. (C)</p> Signup and view all the answers

Which of the following conditions can lead to the progression of NAFLD?

<p>Obesity (D)</p> Signup and view all the answers

What was the percentage increase of ALT to ≥3 × ULN in the placebo arm compared to the resmetirom arms?

<p>1.9% (B)</p> Signup and view all the answers

What was the P-value indicating the significance of the treatment difference at week 52 between resmetirom and placebo?

<p>P &lt; 0.0001 (A)</p> Signup and view all the answers

Which ELF score baseline indicates a subset of patients evaluated for the resmetirom treatment efficacy?

<blockquote> <p>9.8 (D)</p> </blockquote> Signup and view all the answers

In the study, the levels of reverse triiodothyronine were noted to be reduced in which treatment group?

<p>Resmetirom arms (A)</p> Signup and view all the answers

What was observed regarding liver enzymes in the resmetirom arms?

<p>They were reduced from baseline over time. (C)</p> Signup and view all the answers

What percentage reduction in LDL-C was observed with 100 mg of resmetirom treatment at week 24?

<p>22.0% (A)</p> Signup and view all the answers

What was the defined SHBG response that corresponded to the upper two tertiles?

<p>≥120% increase from baseline (C)</p> Signup and view all the answers

Which lipid parameter showed the greatest reduction at the 80 mg dosage of resmetirom?

<p>Lp(a) (C)</p> Signup and view all the answers

What was the percentage of patients reporting abdominal pain at the onset of ≤12 weeks?

<p>5.3% (C)</p> Signup and view all the answers

Which adverse effect had the highest percentage in the reported data?

<p>COVID-19 (B)</p> Signup and view all the answers

What was the percentage reduction in apoB for patients with LDL-C ≥ 100 mg dl−1 treated with 100 mg of resmetirom?

<p>16.5% (B)</p> Signup and view all the answers

What percentage of patients reported nausea with resmetirom treatment at 80 mg?

<p>18.2% (A)</p> Signup and view all the answers

How was the lower exposure to resmetirom defined in the study?

<p>Less than 12 weeks of treatment (B)</p> Signup and view all the answers

What was the primary end point of the MAESTRO-NAFLD-1 trial?

<p>Incidence of TEAEs not being different between treatment arms (B)</p> Signup and view all the answers

How many patients were screened for the MAESTRO-NAFLD-1 trial?

<p>1,988 patients (C)</p> Signup and view all the answers

What percentage of patients receiving resmetirom reported a TEAE during the trial?

<p>86.1% to 88.4% (B)</p> Signup and view all the answers

Which of the following statements about the patient disposition in the trial is true?

<p>22.6% of patients discontinued from the trial (C)</p> Signup and view all the answers

During the trial, how many serious TEAEs were reported?

<p>70 serious TEAEs (A)</p> Signup and view all the answers

What was the randomization distribution for the DB arms in the trial?

<p>325 for 100 mg, 327 for 80 mg, and 320 for placebo (C)</p> Signup and view all the answers

What were the majority of TEAEs in the study characterized as?

<p>Mild or moderate (D)</p> Signup and view all the answers

What proportion of serious TEAEs were related to COVID-19 pneumonia or diagnosis during the trial?

<p>20% (B)</p> Signup and view all the answers

What was the significant percentage reduction in low-density lipoprotein cholesterol (LDL-C) at the 100 mg resmetirom treatment compared to placebo?

<p>−13.9% (C)</p> Signup and view all the answers

Which of the following was the least squares mean relative reduction in triglycerides (TGs) at the 80 mg resmetirom treatment compared to baseline?

<p>−18.4% (A)</p> Signup and view all the answers

What was the percentage change in hepatic fat at week 52 in the OL 100 mg resmetirom arm?

<p>−51.8% (B)</p> Signup and view all the answers

Which treatment showed a significant reduction in apolipoprotein B (apoB) at 80 mg compared to baseline?

<p>−14.3% (D)</p> Signup and view all the answers

What was the significant reduction in triglycerides (TGs) observed from baseline for the 100 mg resmetirom arm at week 24?

<p>−27.5% (A)</p> Signup and view all the answers

How did the effects of the resmetirom treatment at week 24 compare to the placebo effect?

<p>The effects were significantly greater than placebo. (A)</p> Signup and view all the answers

At what dose did the resmetirom treatment achieve a reduction in low-density lipoprotein cholesterol (LDL-C) of −12.4%?

<p>80 mg (A)</p> Signup and view all the answers

What underlying issue was noted that could have impacted treatment adherence in the double-blind arms?

<p>COVID-19-related drug kit delays (A)</p> Signup and view all the answers

What was the percentage of patients who achieved a ≥2 kPa reduction from baseline in the resmetirom arms compared to the placebo arm?

<p>32-55% (C)</p> Signup and view all the answers

What effect did resmetirom treatment have on ALT, AST, and GGT levels in patients with baseline ALT ≥ 30 IU l−1?

<p>Levels were significantly reduced from baseline. (D)</p> Signup and view all the answers

What was the baseline liver stiffness measurement (LSM) threshold criteria used for analysis?

<p>≥7.2 kPa (D)</p> Signup and view all the answers

At week 52, how did the mean change from baseline in VCTE compare between the resmetirom and placebo arms?

<p>Not significantly different. (D)</p> Signup and view all the answers

What correlation was observed with SHBG levels during the treatment period?

<p>SHBG levels plateaued around week 12. (D)</p> Signup and view all the answers

What does an increase in SHBG reflect in relation to resmetirom treatment?

<p>Extent of THR-β activation in the liver. (A)</p> Signup and view all the answers

What was the mean baseline alanine aminotransferase (ALT) level in the studied population?

<p>~37 U l−1 (A)</p> Signup and view all the answers

What was the outcome for patients in the OL 100 mg and DB 100 mg resmetirom arms at week 52 compared to placebo?

<p>They showed a treatment effect directionally. (A)</p> Signup and view all the answers

Flashcards

Nonalcoholic Steatohepatitis (NASH)

A medical condition characterized by fat accumulation in the liver and inflammation, typically found in people with obesity, type 2 diabetes, and dyslipidemia.

Liver Stiffness

A measure of the stiffness of the liver, indicating the extent of fibrosis or scarring in the liver tissue.

Hepatic Fat

The percentage of fat in the liver, often measured using imaging techniques like MRI. Levels exceeding 5% are associated with NASH.

Hepatic Steatosis

The buildup of fatty deposits within the liver, a hallmark of NASH.

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Hepatocyte Injury

A type of liver injury characterized by damage to liver cells, often contributing to the development of NASH.

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Liver Biopsy

An invasive procedure involving the removal of a small piece of liver tissue for examination.

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Dyslipidemia

Elevated levels of low-density lipoprotein cholesterol (LDL-C) or 'bad' cholesterol in the blood.

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Resmetirom

A new drug being investigated for the treatment of NASH, showing promising results in reducing hepatic fat, liver stiffness, and improving lipid profiles.

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Randomized Controlled Trial

A type of clinical trial where participants are randomly assigned to different treatment groups. This helps ensure a fair comparison between treatments.

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Primary Endpoint

The primary outcome of a clinical trial is the main thing researchers are trying to measure. It's the most important result they are looking for.

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TEAEs

Treatment Emergent Adverse Events (TEAEs) are side effects that occur during the course of a clinical trial. They might be caused by the treatment or by some other factor.

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Open-Label Phase

A clinical trial phase where everyone receives the same treatment. This phase usually follows an earlier phase where different treatments were compared.

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Study Completers

In a clinical trial, patients who continue to participate until the end are considered 'completers.' This means they finished all the required study procedures.

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Safety Population

The safety population in a clinical trial includes all participants who received at least one dose of the study drug. It is used to assess the overall safety profile of the drug.

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COVID-19 Pneumonia

COVID-19 pneumonia is a serious complication of the coronavirus infection that affects the lungs.

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Diagnosis Code

A diagnosis code describes a specific medical condition. It is used to track and categorize health information.

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Resmetirom's effect on atherogenic lipid levels

Resmetirom significantly reduced atherogenic lipid levels in patients compared to placebo.

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Specific lipids affected by resmetirom

Low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and triglycerides (TG) levels were all significantly decreased in resmetirom-treated patients compared to placebo.

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Long-term effect on liver fat

Resmetirom demonstrated a sustained reduction in hepatic fat levels over 52 weeks, suggesting a long-term benefit.

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Resmetirom's effect in different study settings

The reduction in hepatic fat was observed in both open-label (OL) and double-blind (DB) treatment arms, indicating consistent results.

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Duration of resmetirom's impact

Resmetirom's positive effects were maintained over 48 weeks, highlighting its potential for long-term management.

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Resmetirom's impact on diverse patients

Subgroup analyses showed that resmetirom effectively reduced hepatic fat in various patient groups, underscoring its broad applicability.

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Resmetirom's impact on hepatic fat measured by CAP

Resmetirom significantly reduced hepatic fat from baseline at week 52 as measured by continuous attenuation parameter (CAP).

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Resmetirom's effectiveness in subgroups

Resmetirom's effectiveness in reducing hepatic fat was observed in all key patient subgroups.

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Weight Loss ≥5%

A decrease in body weight of at least 5% from baseline.

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Sex Hormone-Binding Globulin (SHBG)

A hormone that binds to sex hormones, influencing their activity.

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Exposure to a Drug

A measure of how much a drug reaches its target in the body.

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Lp(a)

A blood lipid associated with an increased risk of heart disease.

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ApoCIII

A protein that carries lipids in the blood.

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ApoB

A protein that carries lipids in the blood.

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LDL-C

A type of cholesterol that can build up in blood vessels, increasing heart disease risk.

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Enhanced Liver Fibrosis (ELF) Score

A measure of liver fibrosis, indicating the extent of scarring.

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ALT Levels

A laboratory test that measures the activity of certain enzymes in the blood, which can be elevated in liver damage.

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What is Liver Stiffness Measurement (LSM)?

A test that measures the stiffness of the liver, indicating the extent of scarring or fibrosis.

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What is Vibration-Controlled Transient Elastography (VCTE)?

A technique used to measure liver stiffness, using vibrations to assess the elasticity of the liver tissue.

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What is SHBG (Sex Hormone Binding Globulin)?

A score that reflects the degree of THR-β activation in the liver, correlating with resmetirom exposure.

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What is Hepatocyte Injury?

A type of liver injury characterized by damage to liver cells, often contributing to the development of NASH.

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What is Hepatic Fat?

A measure of the percentage of fat in the liver, often determined through imaging techniques like MRI.

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What is a Responder Analysis?

A responder analysis focusing on individuals who experience a significant reduction in liver stiffness.

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What is the improvement of Liver Enzymes?

The reduction of liver enzymes, like ALT and AST, indicating improvement in liver health.

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What is Non-Alcoholic Steatohepatitis (NASH)?

A condition characterized by excessive fat accumulation in the liver, inflammation and often progresses to fibrosis.

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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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Related Documents

Resmetirom for Nonalcoholic Fatty Liver Disease: A 2023 A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial PDF

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.

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