FIBRATES SEEM TO BE EQUALLY EFFECTIVE AS SECOND-LINE THERAPY IN PRIMARY BILIARY CHOLANGITIS, WITH BIOCHEMICAL RESPONSE PLATEAUING AT 6 MONTHS

Introduction and Objectives

Approximately 40% of patients with primary biliary cholangitis (PBC) exhibit an incomplete biochemical response to ursodeoxycholic acid (UDCA) and require second-line therapy. Fibrates are widely available in Latin America and commonly used off-label in this setting. We aimed to evaluate clinical and biochemical outcomes in PBC patients with incomplete UDCA response treated with different fibrates.

Materials and Methods

This ongoing, retrospective, multicenter cohort study (ALLATIN), sponsored by ALEH, includes PBC patients from several Latin American countries. For this analysis, only patients with incomplete response (based on biochemical criteria or physician judgment), who received fibrates, were included.

Results

Among 1,204 patients, 342 received fibrates; 263 (76.7%) were treated for incomplete UDCA response (93.2% female; mean age: 50 ± 11 years; 76.5% AMA-positive; 19.6% with cirrhosis). Bezafibrate, fenofibrate, and ciprofibrate were used in 72.2%, 7.2%, and 17.9% of cases. Median ALP before fibrates was 1.9xULN (IQR 1.4-3.0); median time from UDCA start to fibrate use was 30 months (IQR 13-69). At 6 months (n = 153), ALP normalization occurred in 42.5%, while 67.3% and 50.3% met Toronto and POISE criteria, respectively; 30.9% achieved deep response (normal ALP and bilirubin <0.6×ULN). At 12 months (n=150), rates remained stable. No differences were observed across fibrate types (p>0.4). Liver transplantation or death occurred in 24 patients (9.1%) over 87 months (IQR 44-135), associated with cirrhosis at diagnosis (OR 9.9; 95%CI 3.3-29.9; p<0.001) and response at 6 months by Toronto criteria (OR 0.31; 95%CI 0.1-0.9; p=0.035). Discontinuation occurred in 13.7%; adverse events included renal injury (n=1), myalgia (n=4), liver injury (n=4), and abdominal pain (n=4).

Conclusions

Fibrates showed high efficacy regardless of agent used. Biochemical response plateaued by 6 months and predicted long-term outcomes. These findings support early assessment and a pragmatic approach to second-line therapy in PBC, independent of fibrate type.

Conflict of interest: Yes, Gilead and ALEH