Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world

Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world

Background & Aims: Several studies have assessed the short-term effectiveness and safety of obeticholic acid (OCA) in the real-world setting. We aimed to extend knowledge on the real-world effectiveness and safety of OCA treatment by expanding sample size and follow-up, and by exploring chan...

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Main Authors: Francesca Terracciani, Antonio De Vincentis, Daphne D’Amato, Laura Cristoferi, Alessio Gerussi, Pietro Invernizzi, Miki Scaravaglio, Ester Vanni, Daniela Campion, Anna Morgando, Vincenzo Valiani, Vincenzo Boccaccio, Filomena Morisco, Lorenzo Surace, Ilaria Cavalli, Guido Delle Monache, Federico Salomone, Donatella Ieluzzi, Debora Angrisani, Raffaella Tortora, Biagio Cuffari, Alessandra Moretti, Gerardo Nardone, Stefano Fagiuoli, Mauro Viganò, Giovanni Vettori, Federica Cerini, Giancarlo Gimignani, Alberto Mattalia, Fabrizio Pizzolante, Nicoletta De Matthaeis, Cristina Rigamonti, Giulia Francesca Manfredi, Valentina Boano, Paola Begini, Ana Lleo, Francesca Colapietro, Riccardo Plebani, Domenico Alvaro, Rosanna Venere, Elisabetta Degasperi, Marta Borghi, Pietro Lampertico, Edoardo Giovanni Giannini, Sara Labanca, Raffaella Viganò, Federico D'Amico, Antonino Castellaneta, Francesco Squeo, Luca Cadamuro, Luigi Capodicasa, Marco Marzioni, Valerio Buzzanca, Guido Poggi, Alessandro Mussetto, Raffaele Cozzolongo, Francesco Losito, Gaetano Bertino, Maurizio Russello, Mariarita Cannavò, Paolo Scivetti, Maurizio Pompili, Annalisa Tortora, Anna Grazia Niro, Rosa Cotugno, Pietro Pozzoni, Alessia Riva, Luchino Chessa, Michela Miglianti, Giuseppe Cuccorese, Valeria Pace Palitti, Ludovico Abenavoli, Natalia Terreni, Teresa Zolfino, Olivia Morelli, Carlo Saitta, Silvia Casella, Adriano Pellicelli, Maurizia Brunetto, Barbara Coco, Andrea Galli, Fabio Marra, Armando Curto, Annarosa Floreani, Nora Cazzagon, Paolo Rollo, Emanuela Bonaiuto, Loredana Simone, Luigi Muratori, Floriano Rosina, Marco Distefano, Elisa Capello, Valentina Bellia, Rodolfo Sacco, Giuliano Alagna, Leonardo Baiocchi, Lory Saveria Crocé, Chiara Ricci, Paolo Poisa, Antonio Izzi, Sara Boninsegna, Vincenza Calvaruso, Marco Carbone, Umberto Vespasiani-Gentilucci, Giulia Di Pasquale, Paolo Gallo, Cossiga Valentina, Falbo Elisabetta, Tatonetti Riccardo, Musumeci Martina, Christou Chrysanthi, Paolo Villa, Eugenia Pesatori, Alessandro Loglio, Alessandro Conforti, Valentina Feletti, Alessandra Garriba, Evelise Frazzetto, Sara Alecci, Annalisa Ardiri, Martina Costanzo, Francesca Romana Ponziani, Francesca Fianchi, Niccolò Bina, Francesca Zani, Barbara Omazzi, Olga Falco, Jessica Piroddu, Anna Rocca, Paola Carnì, Giuseppe Grassi, Francesco Pezzato, Erica D'Ovidio, Matteo Peviani, Alessandro Bellia, Maria Cristina Sapere, Massimiliano Loreno, Masutti Flora, Fusaro Lisa, Riccardo Perbellini, Roberta Soffredini, Concetta Pitrone, Roberto Filomia, Alba Rocco, Pasquale De Crescenzo, Pasquale Piscitelli, Francesca Toffolon, Fabiana Marchetti, Alessandro Inno, Marco Guarracino, Giovan Giuseppe Di Costanzo, Nicola Alessi, Maria Cristina Neglia, Scudu Chiara
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:JHEP Reports
Subjects:
primary biliary cholangitis
obeticholic acid
real-world evidence
cirrhosis
overlap syndrome
liver stiffness measurement
Online Access:http://www.sciencedirect.com/science/article/pii/S2589555925001260
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Summary:Background &amp; Aims: Several studies have assessed the short-term effectiveness and safety of obeticholic acid (OCA) in the real-world setting. We aimed to extend knowledge on the real-world effectiveness and safety of OCA treatment by expanding sample size and follow-up, and by exploring changes in liver stiffness measurement (LSM) over time. Methods: The RECAPITULATE project involves centres belonging to the “Italian PBC registry” and/or the “Club Epatologi Ospedalieri” PBC working group. Effectiveness was evaluated as biochemical response according to POISE and normal range (NR) criteria (normal alkaline phosphatase/alanine aminotransferase/bilirubin). Safety was assessed as the incidence of de novo/worsening pruritus and discontinuation rate/causes. Available LSMs were also captured. Results: We included 747 patients from 66 Italian centres: mean age 58 years; female/male 88%/14%; median follow-up 24 months [IQR 12-42]; 28% with cirrhosis, and 14% with autoimmune hepatitis (AIH)/PBC overlap syndrome. Probabilities of POISE and NR response increased from baseline to 57% and 20%, respectively, by the 42nd month. The probabilities of response were lower in patients with cirrhosis (p = 0.02 and p = 0.004 for POISE and NR), but not different between patients with AIH/PBC and pure PBC (p = 0.8). Overall, 130 patients (17%) discontinued treatment, mainly due to pruritus (36.9%), while 28.5% did so after developing hepatic events. The discontinuation rate was higher in patients with cirrhosis (p <0.001). LSM was available in 573 patients (∼77%), of whom 255 had multiple measurements. LSM variation over time differed based on the attainment of POISE biochemical response (expected mean annual variation -0.48 [-0.78, -0.19] in responders vs. +0.33 [-0.07, 0.73] in non-responders, respectively, p <0.001). Conclusions: Our findings confirm the effectiveness and safety profiles of OCA in the medium/long term and demonstrate that biochemical response is associated with the change in LSM over time. Impact and Implications: After the conditional approval of OCA for the treatment of PBC, the main confirmatory study failed to demonstrate OCA's ability to reduce liver-related events, leading the EMA to revoke the drug's marketing authorization. The ensuing scientific debate highlights an urgent need for further evidence from real-world practice. In the largest real-world series of patients treated with OCA to date, we confirm that the drug's effectiveness and safety profiles are maintained over a medium-to-long follow-up period. Valuable data for the management of the drug in relevant subgroups of patients, such as those with cirrhosis and autoimmune hepatitis/PBC overlap syndrome, are also provided. Our original results on liver stiffness measurement variation over time suggest a favourable impact of OCA on fibrosis progression, particularly in patients achieving a biochemical response to the drug. Overall, these data provide important insights for clinicians managing patients with PBC and contribute to the ongoing scientific debate about the effectiveness/safety profile of this drug.
ISSN:2589-5559

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