Elafibranor is a peroxisome proliferator-activated receptor (PPAR) agonist, providing a new treatment option for patients with an inadequate response to or intolerance of ursodeoxycholic acid (UDCA).
How Effective is Elafibranor in Treatment?
Core Therapeutic Effects
Elafibranor and its main active metabolite, GFT1007, exert their effects by activating PPAR receptors, with particularly prominent activation of PPAR-α and PPAR-δ.
This unique pharmacological action inhibits bile acid synthesis, thereby improving biochemical parameters in patients with primary biliary cholangitis (PBC).
Although its exact mechanism of action in treating PBC has not been fully elucidated, clinical studies have confirmed its efficacy in reducing alkaline phosphatase (ALP) levels.
Clinical Efficacy Performance
In key clinical trials, elafibranor demonstrated significant biochemical improvement effects.
Compared with the placebo group, PBC patients treated with elafibranor showed a distinct advantage in ALP reduction.
The therapeutic effect can be observed as early as 4 weeks after the start of treatment and can be sustained for up to 52 weeks.
Beyond improving ALP, elafibranor also exerts a positive impact on other liver function indicators.
Elafibranor Use in Special Populations
Patients with Hepatic Impairment
Patients with mild hepatic impairment (Child-Pugh Class A) do not require dosage adjustment.
However, elafibranor is not recommended for patients with decompensated cirrhosis (e.g., presenting with ascites, variceal bleeding, or hepatic encephalopathy).
Patients with moderate to severe hepatic impairment (Child-Pugh Class B or C) should be considered for treatment discontinuation.
Patients with Renal Impairment
Patients with mild to severe renal impairment do not require dosage adjustment, including those with severe renal impairment who are not receiving dialysis.
Pregnant and Lactating Women
Elafibranor may cause fetal harm and is contraindicated in pregnant women.
Before initiating treatment, it is necessary to confirm that women of childbearing potential are not pregnant. Effective contraceptive measures should be taken during treatment and for 3 weeks after treatment discontinuation.
Lactating women should not breastfeed during treatment and for 3 weeks after the last dose of elafibranor.
Medication Monitoring for Elafibranor
Pre-Treatment Assessment
Conduct a detailed inquiry about a history of muscle pain or myopathy.
Confirm the pregnancy status of women of childbearing potential.
Evaluate liver function (alanine transaminase [ALT], aspartate transaminase [AST], total bilirubin [TB], alkaline phosphatase [ALP]).
Review concurrent medications, with special attention to the use of statins, bile acid sequestrants, and rifampicin.
Monitoring for Muscle-Related Adverse Reactions
Elafibranor may cause myalgia, myopathy, and even rhabdomyolysis, with an increased risk particularly when used concomitantly with HMG-CoA reductase inhibitors (statins).
Muscle symptoms should be evaluated regularly, and creatine phosphokinase (CPK) testing should be performed if necessary.
Treatment should be discontinued if new or worsening muscle symptoms occur.
Liver Function Monitoring
Liver function (ALT, AST, TB, ALP) should be monitored regularly during treatment.
If liver function deterioration or clinical symptoms of hepatitis (e.g., jaundice, right upper abdominal pain, eosinophilia) occur, treatment should be discontinued.
If liver function deteriorates again after resuming treatment, permanent treatment discontinuation should be considered.
Fracture Risk Monitoring
Elafibranor may increase the risk of fractures. Bone health should be monitored and maintained in accordance with current standards, especially for patients with pre-existing osteoporosis risk factors.
Allergic Reaction Monitoring
Permanent treatment discontinuation is required if a severe allergic reaction occurs.
For mild to moderate allergic reactions, treatment can be interrupted and symptomatic management provided. After symptom resolution, re-administration may be considered; however, if the allergic reaction recurs, permanent treatment discontinuation is necessary.
