Abigail Brooks is an assistant editor for 

She joined MJH Life Sciences in August 2023 shortly after graduating from Monmouth University where she earned her BA in Communication with a concentration in Public Relations/Journalism and later an MA in Interactive Digital Media. She enjoys traveling, running, and reading books. She can be reached at abrooks@mjhlifesciences.com.

Abigail Brooks, MA

Barritt reviews real-world data about the use and benefits of GLP-1 RAs in patients with MASLD.

A. Sidney Barritt, MD: Real-World Data Suggest Benefit of GLP-1 RAs for MASLD

New research is providing clinicians with an overview of the characteristics and disease progression of patients with 

metabolic dysfunction associated steatotic liver disease (MASLD)

 who were prescribed GLP-1 RAs in real-world settings.

Findings from the analysis of the TARGET-NASH cohort were presented at 

The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD)

 in San Diego, California, by A. Sidney Barritt, MD, a professor at the University of North Carolina and director of hepatology at the University of North Carolina Liver Center, and suggest use of these agents is associated with a reduced risk of all-cause mortality and progression from compensated to decompensated MASH cirrhosis.

“GLP-1 receptor agonists are already FDA-approved for use in diabetes and for obesity. As these are the 2 main risk factors for MASLD and MASH, we're already using these drugs in patients with MASLD and MASH,” Barritt explained to 

. “These medications have already been in play in this patient population, so one of the reasons why we did the study that we did is to look and see if these medications actually impact hard measurable outcomes that patients are interested in.”

Among 6603 TARGET-NASH participants, 4219 met analysis criteria for MASL (n = 1311), MASH (n = 1331), and MASH cirrhosis (n = 1577), 375 of whom were GLP-1 RA users. Investigators noted GLP-1 RA users more commonly had 

, were enrolled at an endocrinology site, and had 

Overall, 20 (5%) GLP-1 RA users died and 33 (20%) progressed from compensated to decompensated cirrhosis vs 243 (6%) and 217 (23%) non-users, respectively, and the median times to decompensation were 24.2 and 21.2 months. Adjusted hazard ratios (HR) indicated higher risk for all-cause mortality and progression from compensated to decompensated cirrhosis for GLP-1 RA non-users compared to users (HR, 2.28; 95% CI, 1.43-3.60 vs HR, 1.69; 95% CI, 1.16-2.46).

Investigators pointed out participants with type 2 diabetes, hypertension, and those who were >60 years of age had a greater risk of all-cause mortality than those without these risk factors, and those with hypertension were at a greater risk of progression to decompensation.

“What this research shows us is that in real-world clinical practice, number 1, we're already using these medications, and number 2, we have a signal here that they will influence these hard patient-important outcomes like symptomatic liver disease, decompensated liver disease, and mortality,” Barritt said.

Barritt A, Mospan A, Munoz B, et al. Use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in patients with MASLD in a real-world setting is associated with slower disease progression and lower all-cause mortality. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.

Target RWE. TARGET-NASH. Accessed November 19, 2024. 

https://www.targetrwe.com/unique-data/registries/target-nash/

Videos

Kowdley reviews open-label extension data for biochemical response, ALP normalization, and pruritus improvement from the phase 3 ELATIVE study.

Kris Kowdley, MD: Elafibranor Remains Safe, Efficacious for PBC Through 3 Years

Open-label extension data from the ongoing phase 3 ELATIVE study is providing clinicians with an overview of the long-term benefit of second-line treatment with elafibranor (Iqirvo) for 

The findings were presented in a late-breaking abstract at 

 in San Diego, California, by Kris Kowdley, MD, director of the Liver Institute Northwest, and demonstrate sustained improvements in biomarkers of cholestasis and pruritus, stabilization of surrogates for fibrosis, and improvements in pruritus up to 3 years.

“The way we treat PBC is evolving,” Kowdley explained in an interview with 

, describing how the addition of obeticholic acid (Ocaliva) as the first second-line therapy in 2016 sparked a major shift in treatment that further changed with the addition of elafibranor. “We used to put patients on ursodeoxycholic acid and hope for the best… [now] our goal is to try to reduce alkaline phosphatase levels as much as possible and to normalize them.”

On June 10, 2024, elafibranor became the first US Food and Drug Administration-approved peroxisome proliferator-activated receptor (PPAR) agonist indicated for the second-line treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. The decision was based on a reduction of alkaline phosphatase (ALP) observed in the multi-center, randomized, double-blind, placebo-controlled phase 3 ELATIVE trial evaluating the efficacy and safety of elafibranor 80 mg once daily versus placebo.

Now, interim data from the ELATIVE open-label extension add to this understanding of elafibranor for the treatment of PBC, suggesting it leads to sustained improvements in biomarkers of cholestasis and pruritus and stabilization of surrogates for fibrosis up to week 156 while remaining well-tolerated.

“This open-label extension study shows that we can maintain the response, more patients will achieve that response, more patients can achieve alkaline phosphatase normalization, and we're seeing improvement in pruritus, which is very reassuring for both telling the patients that they're reducing their risk of adverse long term outcomes but also helping to modify or mitigate their symptoms,” Kowdley said.

Editors’ note: Kowdley has relevant disclosures with CymaBay, Genfit, Gilead, Intercept, Ipsen, Madrigal, Mirum, Pfizer, NovoNordisk, 89Bio, AbbVie, and 

Kowdley K, Bowlus CL, Levy C, et al. 5041 - Long-term efficacy and safety of elafibranor in primary biliary cholangitis: Interim results from the open-label extension of the ELATIVE® trial up to 3 years. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.

Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed November 18, 2024. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc

Articles

The ongoing phase 3 ELATIVE study highlights the long-term benefits of elafibranor as a second-line treatment for primary biliary cholangitis (PBC). Presented at The Liver Meeting 2024, the study shows sustained improvements in cholestasis biomarkers, pruritus, and fibrosis stabilization over three years. Elafibranor, approved by the FDA in June 2024, is the first PPAR agonist for PBC treatment, either in combination with or as an alternative to ursodeoxycholic acid. The open-label extension data further supports its efficacy and tolerability, offering reassurance for patients and clinicians.

Findings from interim analyses of the ongoing open-label extension of the phase 3 ELATIVE study highlight the sustained safety and efficacy of elafibranor (Iqirvo) for the treatment of 

, specifically calling attention to the peroxisome proliferator-activated receptor (PPAR) agonist’s impact on pruritus and fatigue for up to 3 years.

The data were presented in a pair of late-breaking abstracts at 

 in San Diego, California, and report on biomarkers of cholestasis, stabilization of surrogate markers of liver fibrosis, and moderate-to-severe pruritus data for 3 years in patients treated with elafibranor. Additionally, exploratory endpoints for fatigue and sleep were assessed using patient-reported outcomes tools.

“Over 3 years, Iqirvo data suggest sustained efficacy and support the safety profile of the medicine. Importantly, when patients tell me they are less impacted by itch and fatigue—that matters to me as a physician,” Kris Kowdley, MD, director at The Liver Institute Northwest and a primary investigator on the ELATIVE study, said in a press release.

“Treatment with Iqirvo had an impact on symptoms of pruritus and surrogate markers of fibrosis, which are important findings for people living with PBC.”

The open-label extension included 138 patients who completed the double-blind period of the phase 3 ELATIVE study. The interim analysis presented at AASLD was performed after ≥ 1 year of treatment with elafibranor in the open-label extension, for up to 3 years total.

In patients receiving 3 years of continuous treatment with elafibranor across the double-blind period and open-label extension (n = 13), 85% had a biochemical response, defined as alkaline phosphatase (ALP) <1.67 x ULN with ≥ 15% reduction from baseline and total bilirubin ≤ ULN, and 39% achieved ALP normalization at week 156.

Surrogate markers of liver fibrosis, liver stiffness measurements (n = 23), and enhanced liver fibrosis (ELF) (n = 19) scores suggest stabilization when measured from baseline to week 130. In patients continuously receiving elafibranor for up to 156 weeks, pruritus improvements were sustained for patients with moderate or severe pruritus at baseline (n = 5).

Additionally, the impact of elafibranor on fatigue and sleep was investigated as an exploratory endpoint in the open-label extension. Changes in fatigue or sleepiness were reviewed from baseline to week 104 looking at the minimal clinically important differences and categorical changes (n = 48). Results showed fatigue and sleep improvements for patients treated with elafibranor were observed at week 104 across 3 patient-reported outcome (PRO) tools.

In patients with moderate-to-severe fatigue or excessive sleepiness at baseline, clinically meaningful improvements were observed after 104 weeks of treatment with elafibranor in 56% of patients according to the PRO Measurement Information System Fatigue Short Form 7a; 50% of patients according to the fatigue domain of the PBC-40; and 69% of patients according to the Epworth Sleepiness Scale.

“Fatigue is a symptom often reported by people living with PBC and is also very challenging to manage,” Mark Swain, MD, a professor in the department of medicine at Cumming School of Medicine at the University of Calgary, said in a press release.

 “Patients treated with Iqirvo reported improvement in fatigue and sleep, across several patient-reported outcome measures.”

Ipsen. Iqirvo® (elafibranor) data shows efficacy and safety for up to 3 years in patients with PBC with improvements in fatigue and pruritus. November 15, 2024. Accessed November 19, 2024. https://www.ipsen.com/us/press-releases/iqirvo-elafibranor-data-shows-efficacy-and-safety-for-up-to-3-years-in-patients-with-pbc-with-improvements-in-fatigue-and-pruritus-2982128/

Swain M, Jones D, Levy C, et al. 5042 - Impact of elafibranor on fatigue in patients with primary biliary cholangitis: Interim results from the long-term open-label extension of the ELATIVE® trial. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.

Interim analyses from the ELATIVE study's open-label extension underscore the sustained safety and efficacy of elafibranor for primary biliary cholangitis (PBC) over three years. The study highlights the drug's impact on pruritus, fatigue, and surrogate markers of liver fibrosis. Data presented at The Liver Meeting 2024 reveal that 85% of patients achieved a biochemical response, with significant improvements in pruritus, fatigue, and sleep. These findings are supported by patient-reported outcomes, indicating clinically meaningful improvements in symptoms for those with moderate-to-severe baseline conditions.

Findings from the open-label extension of the ELATIVE study suggest sustained safety and efficacy for up to 3 years, with improvements in itch and sleep. 

Elafibranor Shows Sustained Efficacy for PBC, Improves Pruritus and Fatigue

 is associated with an increased risk of poor clinical outcomes, including transplant-free survival, in patients with 

, according to findings from a recent study.

 in San Diego, California, by Ellen Werner, a PhD student at Erasmus University Medical Center, and suggests diabetes is an independent predictor of unfavorable transplant-free survival in patients with PBC.

Recent US Food and Drug Administration accelerated approvals of elafibranor (Iqirvo) and seladelpar (Livdelzi) have helped reshape PBC care, greatly expanding the treatment options available to patients. Understanding which patients are at the greatest risk of adverse disease outcomes is important for appropriate disease management.

Citing the increasing presence of metabolic comorbidities in patients with primary liver diseases, Werner and colleagues sought to assess the relationship between diabetes and clinical outcomes in patients with PBC by analyzing data from the Dutch PBC Cohort Study (DPCS), a retrospective study including every identifiable patient with PBC in the Netherlands from 1990 up to last data collection (2019-2022) in 71 Dutch hospitals.

clinical data through medical chart review. The study’s primary endpoint was liver transplantation or all-cause mortality, and the secondary liver-specific endpoint was the first occurrence of either decompensated cirrhosis, liver transplant, or liver-related death.

In total, 4256 patients with PBC were followed for a median duration of 8.9 years (IQR, 4.2-14.8). Among the cohort, the median age at diagnosis was 56.7 years (IQR 48.4-66.2), 88.2% of participants were female, and 9.8% had diabetes at baseline. Investigators noted patients with diabetes were older (63.6 years vs 56.0 years; 

<.001), were more often male (17.7% vs 11.3%; 

<.001), and more frequently had cirrhosis at baseline (14.6% vs 5.8%; 

The Paris-2 response rate, defined as alkaline phosphatase (ALP) and aspartate transferase (AST) <1.5ULN as well as bilirubin <ULN, after 1 year of ursodeoxycholic acid (UDCA) was 55.2% among patients with diabetes compared with 57.6% among those without diabetes (

= .447). The 10-year transplant-free survival was 70.7% (95% CI, 65.2-76.2) among patients with diabetes compared with 87.0% (95% CI, 85.8-88.2) in those without diabetes (

After 10 years, investigators noted the cumulative liver-specific event rate was 14.6% (95% CI, 10.3-18.9) vs 6.9% (95% CI, 5.9-7.9) in those with and without diabetes, respectively (

<.001). After adjusting for age; gender; cirrhosis; calendar time; and biochemical parameters of liver disease severity, diabetes was independently associated with an increased risk of liver transplant or death (adjusted hazard ratio [aHR], 1.7; 95% CI, 1.3-2.2; 

<.001) and with liver-specific events (aHR, 1.6; 95% CI, 1.0-2.5; 

“In this nationwide cohort, diabetes was an independent predictor of unfavorable liver transplant-free survival in patients with PBC. This is partly explained by an increase in progression to end-stage liver disease,” investigators concluded.

Werner E, Weijsters GHX, van Hooff MCB, et al. Diabetes mellitus is associated with worse clinical outcomes in patients with primary biliary cholangitis. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.

Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. 

. June 10, 2024. Accessed November 18, 2024. 

Brooks, A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. 

. August 14, 2024. Accessed November 18, 2024. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis

Diabetes significantly impacts clinical outcomes in patients with primary biliary cholangitis (PBC), increasing the risk of liver transplant or death. A study presented at The Liver Meeting 2024 analyzed data from the Dutch PBC Cohort Study, revealing that diabetes is an independent predictor of poor transplant-free survival. The study followed 4256 patients, highlighting that those with diabetes had worse outcomes, including a lower 10-year transplant-free survival rate. Adjusted analyses confirmed diabetes as a risk factor for liver-specific events and mortality, emphasizing the need for targeted management strategies.

Diabetes was associated with an increased risk of liver transplant or death and with liver-specific events in patients with PBC.