Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice
Por:
Gómez E, Montero JL, Molina E, García-Buey L, Casado M, Fuentes J, Simón MA, Díaz-González A, Jorquera F, Morillas RM, Presa J, Berenguer M, Conde MI, Olveira A, Macedo G, Garrido I, Hernández-Guerra M, Olivas I, Rodríguez-Tajes S, Londoño M, Sousa JM, Ampuero J, Romero-González E, González-Padilla S, Escudero-García D, Carvalho A, Santos A, Gutiérrez ML, Pérez-Fernández E, Aburruza L, Uriz J, Gomes D, Santos L, Martínez-González J, Albillos A, Fernández-Rodríguez CM
Publicada:
1 jun 2024
Ahead of Print:
1 may 2024
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.
Filiaciones:
Gómez E:
Hospital Universitario 12 de Octubre, Madrid, Spain
Montero JL:
Hospital Universitario Reina Sofía, Córdoba, Spain
Molina E:
Complexo Hospitalario Universitario De Santiago, Coruña, Spain
García-Buey L:
Hospital Universitario de la Princesa, Madrid, Spain
Casado M:
Hospital Universitario de Torrecárdenas, Almería, Spain
Fuentes J:
Hospital Universitario Miguel Servet, Zaragoza, Spain
Simón MA:
Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
University of Zaragoza, Zaragoza, Spain
Díaz-González A:
Hospital Universitario Marqués de Valdecilla, Santander, Spain
Jorquera F:
Complejo Hospitalario de Leon, Leon, Spain
Morillas RM:
Hospital Germans Trias i Pujol, Badalona, Spain
Presa J:
Centro Hospitalar Tras-os-Montes a Alto Douro, Vila Real, Portugal
Berenguer M:
Hospital Universitario La Fe, Valencia, Spain
University of Valencia, Valencia, Spain
Conde MI:
Hospital Universitario La Fe, Valencia, Spain
Olveira A:
Hospital Universitario La Paz, Madrid, Spain
Macedo G:
Serviço de Gastrenterologia Do Centro Hospitalar Universitário São João (CHUSJ), Porto, Portugal
Garrido I:
Serviço de Gastrenterologia Do Centro Hospitalar Universitário São João (CHUSJ), Porto, Portugal
Hernández-Guerra M:
Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
Olivas I:
Hospital Clínic, Barcelona, Spain
Rodríguez-Tajes S:
Hospital Clínic, Barcelona, Spain
Londoño M:
Hospital Clínic, Barcelona, Spain
Sousa JM:
Hospital Universitario Virgen del Rocío, Sevilla, Spain
Ampuero J:
Hospital Universitario Virgen del Rocío, Sevilla, Spain
Instituto De Biomedicina De Sevilla (IBIS), Sevilla, Spain
Romero-González E:
Hospital Clinico Universitario de Valencia, Universidad de Valencia, Valencia, Spain
González-Padilla S:
Hospital Clinico Universitario de Valencia, Universidad de Valencia, Valencia, Spain
Escudero-García D:
Hospital Clinico Universitario de Valencia, Universidad de Valencia, Valencia, Spain
Carvalho A:
Centro Hospitalar e Universitário De Coimbra, Coimbra, Portugal
Santos A:
Centro Hospitalar e Universitário De Coimbra, Coimbra, Portugal
Gutiérrez ML:
Hospital Universitario Fundacion Alcorcon, Alcorcon Madrid, Spain
University Rey Juan Carlos, Madrid, Spain
Pérez-Fernández E:
Hospital Universitario Fundacion Alcorcon, Alcorcon Madrid, Spain
University Rey Juan Carlos, Madrid, Spain
Aburruza L:
Hospital Universitario de Donostia, Donostia-San Sebastián, Spain
Uriz J:
Complejo Hospitalario de Navarra, Pamplona, Spain
Gomes D:
Departamento de Gastrenterología, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal
Santos L:
Departamento de Gastrenterología, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal
Martínez-González J:
Hospital Universitario Ramón y Cajal, Madrid, Spain
Albillos A:
Hospital Universitario Ramón y Cajal, Madrid, Spain
Ramón y Cajal Institute of Health Research, Madrid, Spain
University of Alcalá de Henares, Alcalá de Henares, Spain
Fernández-Rodríguez CM:
Hospital Universitario Fundacion Alcorcon, Alcorcon Madrid, Spain
University Rey Juan Carlos, Madrid, Spain
Green Submitted, Bronze
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