Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis
Copyright © 2023 Massachusetts Medical Society..
BACKGROUND: Primary biliary cholangitis is a rare, chronic cholestatic liver disease characterized by the destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. Whether elafibranor, an oral, dual peroxisome proliferator-activated receptor (PPAR) α and δ agonist, may have benefit as a treatment for primary biliary cholangitis is unknown.
METHODS: In this multinational, phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients with primary biliary cholangitis who had had an inadequate response to or unacceptable side effects with ursodeoxycholic acid to receive once-daily elafibranor, at a dose of 80 mg, or placebo. The primary end point was a biochemical response (defined as an alkaline phosphatase level of <1.67 times the upper limit of the normal range, with a reduction of ≥15% from baseline, and normal total bilirubin levels) at week 52. Key secondary end points were normalization of the alkaline phosphatase level at week 52 and a change in pruritus intensity from baseline through week 52 and through week 24, as measured on the Worst Itch Numeric Rating Scale (WI-NRS; scores range from 0 [no itch] to 10 [worst itch imaginable]).
RESULTS: A total of 161 patients underwent randomization. A biochemical response (the primary end point) was observed in 51% of the patients (55 of 108) who received elafibranor and in 4% (2 of 53) who received placebo, for a difference of 47 percentage points (95% confidence interval [CI], 32 to 57; P<0.001). The alkaline phosphatase level normalized in 15% of the patients in the elafibranor group and in none of the patients in the placebo group at week 52 (difference, 15 percentage points; 95% CI, 6 to 23; P = 0.002). Among patients who had moderate-to-severe pruritus (44 patients in the elafibranor group and 22 in the placebo group), the least-squares mean change from baseline through week 52 on the WI-NRS did not differ significantly between the groups (-1.93 vs. -1.15; difference, -0.78; 95% CI, -1.99 to 0.42; P = 0.20). Adverse events that occurred more frequently with elafibranor than with placebo included abdominal pain, diarrhea, nausea, and vomiting.
CONCLUSIONS: Treatment with elafibranor resulted in significantly greater improvements in relevant biochemical indicators of cholestasis than placebo. (Funded by GENFIT and Ipsen; ELATIVE ClinicalTrials.gov number, NCT04526665.).
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:390 |
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Enthalten in: |
The New England journal of medicine - 390(2024), 9 vom: 29. Feb., Seite 795-805 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Kowdley, Kris V [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 29.02.2024 Date Revised 01.03.2024 published: Print-Electronic ClinicalTrials.gov: NCT04526665 Citation Status MEDLINE |
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doi: |
10.1056/NEJMoa2306185 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM364537140 |
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500 | |a published: Print-Electronic | ||
500 | |a ClinicalTrials.gov: NCT04526665 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 Massachusetts Medical Society. | ||
520 | |a BACKGROUND: Primary biliary cholangitis is a rare, chronic cholestatic liver disease characterized by the destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. Whether elafibranor, an oral, dual peroxisome proliferator-activated receptor (PPAR) α and δ agonist, may have benefit as a treatment for primary biliary cholangitis is unknown | ||
520 | |a METHODS: In this multinational, phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients with primary biliary cholangitis who had had an inadequate response to or unacceptable side effects with ursodeoxycholic acid to receive once-daily elafibranor, at a dose of 80 mg, or placebo. The primary end point was a biochemical response (defined as an alkaline phosphatase level of <1.67 times the upper limit of the normal range, with a reduction of ≥15% from baseline, and normal total bilirubin levels) at week 52. Key secondary end points were normalization of the alkaline phosphatase level at week 52 and a change in pruritus intensity from baseline through week 52 and through week 24, as measured on the Worst Itch Numeric Rating Scale (WI-NRS; scores range from 0 [no itch] to 10 [worst itch imaginable]) | ||
520 | |a RESULTS: A total of 161 patients underwent randomization. A biochemical response (the primary end point) was observed in 51% of the patients (55 of 108) who received elafibranor and in 4% (2 of 53) who received placebo, for a difference of 47 percentage points (95% confidence interval [CI], 32 to 57; P<0.001). The alkaline phosphatase level normalized in 15% of the patients in the elafibranor group and in none of the patients in the placebo group at week 52 (difference, 15 percentage points; 95% CI, 6 to 23; P = 0.002). Among patients who had moderate-to-severe pruritus (44 patients in the elafibranor group and 22 in the placebo group), the least-squares mean change from baseline through week 52 on the WI-NRS did not differ significantly between the groups (-1.93 vs. -1.15; difference, -0.78; 95% CI, -1.99 to 0.42; P = 0.20). Adverse events that occurred more frequently with elafibranor than with placebo included abdominal pain, diarrhea, nausea, and vomiting | ||
520 | |a CONCLUSIONS: Treatment with elafibranor resulted in significantly greater improvements in relevant biochemical indicators of cholestasis than placebo. (Funded by GENFIT and Ipsen; ELATIVE ClinicalTrials.gov number, NCT04526665.) | ||
650 | 4 | |a Clinical Trial, Phase III | |
650 | 4 | |a Journal Article | |
650 | 4 | |a Multicenter Study | |
650 | 4 | |a Randomized Controlled Trial | |
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650 | 7 | |a PPAR alpha |2 NLM | |
650 | 7 | |a PPAR delta |2 NLM | |
650 | 7 | |a Propionates |2 NLM | |
650 | 7 | |a Ursodeoxycholic Acid |2 NLM | |
650 | 7 | |a 724L30Y2QR |2 NLM | |
650 | 7 | |a Cholagogues and Choleretics |2 NLM | |
700 | 1 | |a Bowlus, Christopher L |e verfasserin |4 aut | |
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700 | 1 | |a Akarca, Ulus S |e verfasserin |4 aut | |
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700 | 1 | |a Arrese, Marco |e verfasserin |4 aut | |
700 | 1 | |a Corpechot, Christophe |e verfasserin |4 aut | |
700 | 1 | |a Francque, Sven M |e verfasserin |4 aut | |
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700 | 1 | |a Invernizzi, Pietro |e verfasserin |4 aut | |
700 | 1 | |a Jones, David |e verfasserin |4 aut | |
700 | 1 | |a Kruger, Frederik C |e verfasserin |4 aut | |
700 | 1 | |a Lawitz, Eric |e verfasserin |4 aut | |
700 | 1 | |a Mayo, Marlyn J |e verfasserin |4 aut | |
700 | 1 | |a Shiffman, Mitchell L |e verfasserin |4 aut | |
700 | 1 | |a Swain, Mark G |e verfasserin |4 aut | |
700 | 1 | |a Valera, José Miguel |e verfasserin |4 aut | |
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700 | 1 | |a Mazain, Sarah |e verfasserin |4 aut | |
700 | 1 | |a Rafailovic, Dragutin |e verfasserin |4 aut | |
700 | 1 | |a Taddé, Bachirou |e verfasserin |4 aut | |
700 | 1 | |a Miller, Benjamin |e verfasserin |4 aut | |
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700 | 1 | |a Galdame, Omar |e investigator |4 oth | |
700 | 1 | |a Moreno, Christophe |e investigator |4 oth | |
700 | 1 | |a Verhelst, Xavier |e investigator |4 oth | |
700 | 1 | |a Cançado, Eduardo Luiz Rachid |e investigator |4 oth | |
700 | 1 | |a Faisal, Nabiha |e investigator |4 oth | |
700 | 1 | |a Vincent, Catherine |e investigator |4 oth | |
700 | 1 | |a Mezzano, Gabriel |e investigator |4 oth | |
700 | 1 | |a Poniachik, Jaime |e investigator |4 oth | |
700 | 1 | |a Ratziu, Vlad |e investigator |4 oth | |
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700 | 1 | |a Sogni, Philippe |e investigator |4 oth | |
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700 | 1 | |a Calvaruso, Vincenza |e investigator |4 oth | |
700 | 1 | |a Muratori, Luigi |e investigator |4 oth | |
700 | 1 | |a Rajabally, Naayil |e investigator |4 oth | |
700 | 1 | |a Sonderup, Mark |e investigator |4 oth | |
700 | 1 | |a Ampuero, Javier |e investigator |4 oth | |
700 | 1 | |a Calleja Panero, José Luis |e investigator |4 oth | |
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700 | 1 | |a Londoño Hurtado, María Carlota |e investigator |4 oth | |
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700 | 1 | |a Salcedo Plaza, Magdalena |e investigator |4 oth | |
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