HIGH RATE OF EARLY ALP NORMALIZATION WITH UDCA–BEZAFIBRATE COMBINATION THERAPY IN TREATMENT-NAÏVE PRIMARY BILIARY CHOLANGITIS: PRELIMINARY RESULTS

Abstract

Introduction and Objectives

 Six-month alkaline phosphatase (ALP) normalisation predicts one-year response and survival in primary biliary cholangitis (PBC). Bezafibrate (BZF) benefits incomplete ursodeoxycholic-acid (UDCA) responders. We therefore assessed ALP normalization at six-month with UDCA alone versus UDCA+BZF at two different doses.

Materials and Methods

in an open-label trial (January 2022–2025) antimitochondrial-antibody–positive, non-cirrhotic PBC patients were randomised 2 : 2 : 1 to UDCA 13–15 mg kg⁻¹ day⁻¹ (n=21), UDCA+BZF 400 mg (n=23) or UDCA+BZF 800 mg (n=8). Liver tests were obtained monthly for six months. The primary end point was ALP ≤ 1 × ULN at month 6; secondary end points were changes in other enzymes, pruritus and safety.

Results

 Fifty-two patients (94 % female, 57 ± 11 years, BMI 25 ± 6 kg m⁻², histological stages 1(n23)/2(n16/3(n13) completed follow-up. ALP normalised in 36 % with UDCA, 78 % with UDCA+BZF 400 mg and 100 % with UDCA+BZF 800 mg (χ² < 0.01). Mean ALP (× ULN) at six months was 1.5±0.7 (UDCA), 0.98±0.2 (UDCA+BZF 400 mg), and 0.8±0.2 (UDCA+BZF 800 mg) (ANOVA p<0.001). Linear mixed-effects analysis showed significant time-dependent ALP declines in all groups; BZF intensified these monthly slopes (β = –0.34 for 400 mg, –0.44 for 800 mg vs UDCA, both Tukey-adjusted p<0.01). Pruritus persisted in 14 % of UDCA recipients but in none on BZF, and renal function and creatine kinase were unchanged across groups.

Conclusions

Up-front UDCA+BZF achieves dose-dependent, near-universal six-month ALP normalisation and accelerates biochemical improvement without early safety concerns. These interim data support initiating combination therapy at diagnosis, particularly in symptomatic PBC.