P-77 TRIPLE THERAPY FOR DIFFICULT-TO-TREAT PRIMARY BILIARY CHOLANGITIS: A SYSTEMATIC REVIEW AND SINGLE-ARM META-ANALYSIS

Conflict of interest

No

Introduction and Objectives

High-risk patients with primary biliary cholangitis (PBC) who respond incompletely to ursodeoxycholic acid (UDCA) require additional treatment with fibrates or obeticholic acid (OCA). Despite this, 30-50% of these patients continue to exhibit elevated alkaline phosphatase (ALP) and bilirubin levels, classifying them as difficult-to-treat PBC. This study aims to evaluate the effects of triple therapy (UDCA + OCA + fibrates) on liver biochemistry in patients with difficult-to-treat PBC.

Patients / Materials and Methods

We systematically reviewed EMBASE, PubMed, and Cochrane databases to identify eligible studies. Pooled analyses were performed for change-from-baseline data. We also conducted subgroup analyses based on the sequencing of the specific add-on drug used as third-line therapy. Statistical analyses were performed using RStudio (2023.12.1+402).

Results and Discussion

Two studies provided change-from-baseline data, encompassing 95 patients under triple therapy, of whom 68.4% (n=65) had fibrates added to UDCA+OCA dual therapy. Overall, patients under triple therapy presented with decreased ALP [-0.82 x upper limit of normal (ULN), 95%CI -0.96 to -0.68], bilirubin (-0.06 x ULN; 95%CI -0.11 to -0.01), and GGT (-3.18 x ULN; 95%CI -4.57 to -1.79) levels compared to the last available result on dual therapy. No significant change was noted for AST (-0.08 x ULN; 95%CI -0.44 to 0.28) and ALT (-0.21 x ULN; 95%CI -0.61 to 0.20) concentrations. However, the addition of OCA to UDCA+fibrates dual therapy significantly reduced AST (-0.53 x ULN; 95%CI -0.73 to -0.33; p-value for subgroup differences < 0.001) and ALT (-0.69 x ULN; -0.97 to -0.40; p<0.001) levels. On the other hand, adding fibrates to the UDCA+OCA scheme was superior in reducing ALP levels (p=0.049).

Conclusions

Triple therapy appears to reduce liver enzyme levels in patients with difficult-to-treat PBC. Further studies are warranted to clarify the optimal sequencing and to identify the subgroups that benefit the most from this combination therapy.