Obeticholic Acid vs Fibrates as Second-Line Therapy for Primary Biliary Cholangitis: Systematic Review and Meta-Analysis.

BACKGROUND

Around 40% of patients diagnosed with Primary Biliary Cholangitis (PBC) experience a suboptimal biochemical response to ursodeoxycholic acid (UDCA).

AIMS: We aimed to compare fibrates and obeticholic acid (OCA) as add-on second-line therapy and evaluate whether these drugs hold superiority over each other.

METHODS

We systematically searched Embase, MEDLINE, and Cochrane CENTRAL for studies comparing fibrates and OCA published by May 6, 2024. A pooled analysis was conducted to evaluate changes in liver biochemistry and response rates based on validated criteria. Data were expressed as mean difference (MD) for continuous outcomes and as Odds Ratio (OR) when binary.

RESULTS

We included 883 patients from 4 studies, 468 (53.0%) under UDCA + OCA. Follow-up time ranged from 6 to 12 months. Patients treated with fibrates have similar mean bilirubin post-intervention values (MD 0.11 × upper limit of normal [ULN]; 95% CI - 0.26 to 0.49) compared to OCA. However, fibrates demonstrated superiority over OCA for percentual reduction in ALP compared to baseline (MD 20.13%; 95% CI 11.84-28.41), ALP post-intervention values (MD - 0.59 xULN; 95% CI - 1.02 to - 0.15), and rate of ALP normalization (OR 32.34; 95% CI 14.54-71.92). Patients treated with fibrates also more frequently met Barcelona (OR 4.28; 95% CI 2.26-8.11), POISE (OR 5.48; 95% CI 2.70-11.13), and Paris II (OR 5.88; 95% CI 3.96-8.74) response criteria.

CONCLUSION

In patients with PBC and an incomplete response to UDCA, fibrates seem to be associated with greater ALP reduction and achievement of response criteria compared to OCA.