Gómez, E.Montero, J.L.Molina, E.García-Buey, L.Casado, M.Fuentes, J.Simón, M.A.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.Alburruza, L.Uriz, J.Gomes, D.Santos, L.Martínez-González, J.Albillos, A.Fernández-Rodríguez, C.M.2024-06-282024-06-282024-05-01Gómez E, Montero JL, Molina E, García-Buey L, Casado M, Fuentes J, et al. Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice. Aliment Pharmacol Ther. 2024; 59: 1604–1615. https://doi.org/10.1111/apt.180041365-2036 (online)0269-2813 (print)https://hdl.handle.net/10115/35624Background 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 hypertensionengAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/article10.1111/apt.18004info:eu-repo/semantics/openAccess