Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice

Gómez, E. ; Montero, J. L. ; Molina, E. ; García-Buey, L. ; Casado, M. ; Fuentes, J. (Universidad de Zaragoza) ; Simón, M. A. (Universidad de Zaragoza) ; Díaz-González, A. ; Jorquera, F. ; Morillas, R. M. ; Presa, J. ; Berenguer, M. ; Conde, M. I. ; Olveira, A. ; Macedo, G. ; Garrido, I. ; Hernández-Guerra, M. ; Olivas, I. ; Rodríguez-Tajes, S. ; Londoño, M. ; Sousa, J. M. ; Ampuero, J. ; Romero-González, E. ; González-Padilla, Sh. ; Escudero-García, D. ; Carvalho, A. ; Santos, A. ; Gutiérrez, M. L. ; Pérez-Fernández, E. ; Aburruza, L. ; Uriz, J. ; Gomes, D. ; Santos, L. ; Martínez-González, J. ; Albillos, A. ; Fernández-Rodríguez, C. M.

Resumen: Background
Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain.
Aims
To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation).
Methods
We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates.
Results
Of 255 patients, median follow-up was 35.1 months (IQR: 20.2–53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension.
Conclusion
Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Idioma: Inglés

DOI: 10.1111/apt.18004

Año: 2024

Publicado en: ALIMENTARY PHARMACOLOGY & THERAPEUTICS (2024), [12 pp.]
ISSN: 0269-2813

Tipo y forma: Article (Published version)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)