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-Taje, 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 and 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:
 Hosp Univ 12 Octubre, Madrid, Spain

Montero, JL:
 Hosp Univ Reina Sofia, Cordoba, Spain

Molina, E:
 Complexo Hosp Univ Santiago, Coruna, Spain

García-Buey, L:
 Hosp Univ La Princesa, Madrid, Spain

Casado, M:
 Hosp Univ Torrecardenas, Almeria, Spain

Fuentes, J:
 Hosp Univ Miguel Servet, Zaragoza, Spain

Simón, MA:
 Hosp Clin Univ Lozano Blesa, Zaragoza, Spain

 Univ Zaragoza, Zaragoza, Spain

Díaz-González, A:
 Hosp Univ Marques Valdecilla, Santander, Spain

Jorquera, F:
 Complejo Hosp Leon, Leon, Spain

:
 Hosp Badalona Germans Trias & Pujol, Badalona, Spain

Presa, J:
 Ctr Hosp Tras Os Montes Alto Douro, Vila Real, Portugal

Berenguer, M:
 Hosp Univ La Fe, Valencia, Spain

 Univ Valencia, Valencia, Spain

Conde, MI:
 Hosp Univ La Fe, Valencia, Spain

Olveira, A:
 Hosp Univ La Paz, Madrid, Spain

Macedo, G:
 CHU Sao Joao CHUSJ, Serv Gastrenterol, Porto, Portugal

Garrido, I:
 CHU Sao Joao CHUSJ, Serv Gastrenterol, Porto, Portugal

Hernández-Guerra, M:
 Hosp Univ Canarias, Santa Cruz De Tenerife, Spain

Olivas, I:
 Hosp Clin Barcelona, Barcelona, Spain

Rodríguez-Taje, S:
 Hosp Clin Barcelona, Barcelona, Spain

Londoño, M:
 Hosp Clin Barcelona, Barcelona, Spain

Sousa, JM:
 Hosp Univ Virgen Rocio, Seville, Spain

Ampuero, J:
 Hosp Univ Virgen Rocio, Seville, Spain

 Inst Biomed Sevilla IBiS, Seville, Spain

Romero-González, E:
 Univ Valencia, Hosp Clin Univ Valencia, Valencia, Spain

González-Padilla, S:
 Univ Valencia, Hosp Clin Univ Valencia, Valencia, Spain

Escudero-García, D:
 Univ Valencia, Hosp Clin Univ Valencia, Valencia, Spain

Carvalho, A:
 Ctr Hosp & Univ Coimbra, Coimbra, Portugal

Santos, A:
 Ctr Hosp & Univ Coimbra, Coimbra, Portugal

Gutiérrez, ML:
 Hosp Univ Fdn Alcorcon, Madrid, Spain

 Univ Rey Juan Carlos, Madrid, Spain

Pérez-Fernández, E:
 Hosp Univ Fdn Alcorcon, Madrid, Spain

 Univ Rey Juan Carlos, Madrid, Spain

Aburruza, L:
 Hosp Univ Donostia, Donostia San Sebastian, Spain

Uriz, J:
 Complejo Hosp Navarra, Pamplona, Spain

Gomes, D:
 CHU Coimbra, Dept Gastrenterol, Coimbra, Portugal

Santos, L:
 CHU Coimbra, Dept Gastrenterol, Coimbra, Portugal

Martínez-González, J:
 Hosp Univ Ramon & Cajal, Madrid, Spain

Albillos, A:
 Hosp Univ Ramon & Cajal, Madrid, Spain

 Ramon & Cajal Inst Hlth Res, Madrid, Spain

 Univ Alcala de Henares, Alcala De Henares, Spain

Fernández-Rodríguez, CM:
 Univ Rey Juan Carlos, Hosp Univ Fdn Alcorcon, Madrid, Spain

 Hosp Univ Fdn Alcorcon, Madrid, Spain

 Univ Rey Juan Carlos, Madrid, Spain
ISSN: 02692813





ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Editorial
Blackwell Publishing Inc., 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Reino Unido
Tipo de documento: Article
Volumen: 59 Número: 12
Páginas: 1604-1615
WOS Id: 001214941200001
ID de PubMed: 38690746
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