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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2025-08-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Francesca Terracciani |
| collection | DOAJ |
| description | 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 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. |
| format | Article |
| id | doaj-art-4ff5bdeefebe4c65a08b587826154b1b |
| institution | DOAJ |
| issn | 2589-5559 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj-art-4ff5bdeefebe4c65a08b587826154b1b2025-08-20T03:16:57ZengElsevierJHEP Reports2589-55592025-08-017810144810.1016/j.jhepr.2025.101448Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-worldFrancesca Terracciani0Antonio De Vincentis1Daphne D’Amato2Laura Cristoferi3Alessio Gerussi4Pietro Invernizzi5Miki Scaravaglio6Ester Vanni7Daniela Campion8Anna Morgando9Vincenzo Valiani10Vincenzo Boccaccio11Filomena Morisco12Lorenzo Surace13Ilaria Cavalli14Guido Delle Monache15Federico Salomone16Donatella Ieluzzi17Debora Angrisani18Raffaella Tortora19Biagio Cuffari20Alessandra Moretti21Gerardo Nardone22Stefano Fagiuoli23Mauro Viganò24Giovanni Vettori25Federica Cerini26Giancarlo Gimignani27Alberto Mattalia28Fabrizio Pizzolante29Nicoletta De Matthaeis30Cristina Rigamonti31Giulia Francesca Manfredi32Valentina Boano33Paola Begini34Ana Lleo35Francesca Colapietro36Riccardo Plebani37Domenico Alvaro38Rosanna Venere39Elisabetta Degasperi40Marta Borghi41Pietro Lampertico42Edoardo Giovanni Giannini43Sara Labanca44Raffaella Viganò45Federico D'Amico46Antonino Castellaneta47Francesco Squeo48Luca Cadamuro49Luigi Capodicasa50Marco Marzioni51Valerio Buzzanca52Guido Poggi53Alessandro Mussetto54Raffaele Cozzolongo55Francesco Losito56Gaetano Bertino57Maurizio Russello58Mariarita Cannavò59Paolo Scivetti60Maurizio Pompili61Annalisa Tortora62Anna Grazia Niro63Rosa Cotugno64Pietro Pozzoni65Alessia Riva66Luchino Chessa67Michela Miglianti68Giuseppe Cuccorese69Valeria Pace Palitti70Ludovico Abenavoli71Natalia Terreni72Teresa Zolfino73Olivia Morelli74Carlo Saitta75Silvia Casella76Adriano Pellicelli77Maurizia Brunetto78Barbara Coco79Andrea Galli80Fabio Marra81Armando Curto82Annarosa Floreani83Nora Cazzagon84Paolo Rollo85Emanuela Bonaiuto86Loredana Simone87Luigi Muratori88Floriano Rosina89Marco Distefano90Elisa Capello91Valentina Bellia92Rodolfo Sacco93Giuliano Alagna94Leonardo Baiocchi95Lory Saveria Crocé96Chiara Ricci97Paolo Poisa98Antonio Izzi99Sara Boninsegna100Vincenza Calvaruso101Marco Carbone102Umberto Vespasiani-Gentilucci103Giulia Di PasqualePaolo GalloCossiga ValentinaFalbo ElisabettaTatonetti RiccardoMusumeci MartinaChristou ChrysanthiPaolo VillaEugenia PesatoriAlessandro LoglioAlessandro ConfortiValentina FelettiAlessandra GarribaEvelise FrazzettoSara AlecciAnnalisa ArdiriMartina CostanzoFrancesca Romana PonzianiFrancesca FianchiNiccolò BinaFrancesca ZaniBarbara OmazziOlga FalcoJessica PirodduAnna RoccaPaola CarnìGiuseppe GrassiFrancesco PezzatoErica D'OvidioMatteo PevianiAlessandro BelliaMaria Cristina SapereMassimiliano LorenoMasutti FloraFusaro LisaRiccardo PerbelliniRoberta SoffrediniConcetta PitroneRoberto FilomiaAlba RoccoPasquale De CrescenzoPasquale PiscitelliFrancesca ToffolonFabiana MarchettiAlessandro InnoMarco GuarracinoGiovan Giuseppe Di CostanzoNicola AlessiMaria Cristina NegliaScudu ChiaraUnit of Clinical Medicine and Hepatology, Fondazione Policlinico Universitario Campus Bio-medico di Roma, Italy; Research Unit of Hepatology, Università Campus Bio-medico di Roma, ItalyUnit of Internal Medicine, Fondazione Policlinico Universitario Campus Bio-medico di Roma, Italy; Research Unit of Internal Medicine, Università Campus Bio-medico di Roma, ItalyGastroenterology Unit, Città della Salute e della Scienza University Hospital, Turin, ItalyDivision of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital, Monza, ItalyDivision of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital, Monza, ItalyDivision of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital, Monza, ItalyDivision of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital, Monza, ItalyGastroenterology Unit, Città della Salute e della Scienza University Hospital, Turin, ItalyGastroenterology Unit, Città della Salute e della Scienza University Hospital, Turin, ItalyGastroenterology Unit, Città della Salute e della Scienza University Hospital, Turin, ItalyU.O.C. Medicina Interna “Pietro Gatti”. P.O. Antonio Perrino. Brindisi, ItalyU.O.C. Medicina Interna “Pietro Gatti”. P.O. Antonio Perrino. Brindisi, ItalyDepartimento di Medicina Clinica e Chirurgia” UO di Malattie del Fegato e delle Vie Biliari” Università di Napoli Federico II, ItalyAmbulatorio di Infettivologia - Epatologia e Valutazione Trapianto Fegato - Distretto di Lamezia Terme - ASP Catanzaro, ItalyUOC Medicina- ASST Cremona, ItalyUOC Medicina Interna, Presidio Ospedaliero ''S. Massimo'', Penne, ASL Pescara, ItalyUOC Gastroenterologia, Ospedale di Acireale, ASP Catania, ItalyUSD Liver Unit, Azienda Ospedaliera Universitaria Integrata di Verona, ItalyHepatology Unit, AORN A. Cardarelli, Naples, ItalyHepatology Unit, AORN A. Cardarelli, Naples, ItalyDivision of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, ItalyAmbulatorio di Epatologia - Osperale San Filippo Neri - ASL RM1 – Roma, ItalyDepartment of Clinical Medicine and Surgery, Gastroenterology, University Federico II, Naples, ItalyGastroenterologia 1 - Epatologia e Trapiantologia, ASST Papa Giovanni XXIII, Piazza OMS, 1 - 24127 Bergamo, ItalyGastroenterologia 1 - Epatologia e Trapiantologia, ASST Papa Giovanni XXIII, Piazza OMS, 1 - 24127 Bergamo, ItalyAzienda Provinciale per i Servizi Sanitari, Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, Trento, ItalyHepatology Unit, San Giuseppe Hospital, Milan, ItalySan Paolo Hospital, Civitavecchia; Padre Pio Hospital Bracciano, ItalyDivision of Gastroenterology, Santa Croce e Carle General Hospital, Cuneo, ItalyCEMAD, Digestive Disease Center, Department of Medical and Surgical Sciences, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, ItalyCEMAD, Digestive Disease Center, Department of Medical and Surgical Sciences, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, ItalyDepartment of Translational Medicine, Università del Piemonte Orientale, Novara, Italy; Division of Internal Medicine, AOU Maggiore della Carità, Novara, ItalyDepartment of Translational Medicine, Università del Piemonte Orientale, Novara, Italy; Division of Internal Medicine, AOU Maggiore della Carità, Novara, ItalyCardinal Massaia Hospital, Asti, ItalyAzienda Ospedaliera (AOU) Sant’Andrea di Roma, ItalyDepartment of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, ItalyDepartment of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, ItalyDepartment of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, ItalyDepartment of Translational and Precision Medicine, University La Sapienza, Rome, ItalyDepartment of Translational and Precision Medicine, University La Sapienza, Rome, ItalyDivision of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDivision of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDivision of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyGastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, ItalyGastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, ItalyNiguarda Hospital, Milan, ItalyNiguarda Hospital, Milan, ItalySection of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, ItalySection of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, ItalyGastroenterology and Hepatology Unit, Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialities, PROMISE, University of Palermo, ItalyGastroenterology and Hepatology Unit, Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialities, PROMISE, University of Palermo, ItalyUniversità Politecnica delle Marche, Ancona, ItalyUniversità Politecnica delle Marche, Ancona, ItalyArea Onco-epatologia Interventistica, Istituti Clinici Pavia-Vigevano, Grupposandonato, ItalyUnit of Gastroenterology, Santa Maria delle Croci Hospital, Ravenna, ItalyGastroenterology Unit, National Institute of Gastroenterology -IRCCS “S de Bellis” Research Hospital-70013 Castellana Grotte, Bari, ItalyGastroenterology Unit, National Institute of Gastroenterology -IRCCS “S de Bellis” Research Hospital-70013 Castellana Grotte, Bari, ItalyUOSD di Epatologia - Policlinico ''G. Rodolico-San Marco” - Dip. Medicina Clinica e Sperimentale, Università di Catania, ItalyU.O.S.D. Epatologia. ARNAS Garibaldi- Nesima, Catania, ItalyU.O.S.D. Epatologia. ARNAS Garibaldi- Nesima, Catania, ItalyAmbulatorio di Epatologia, S.C. di Medicina Interna, Ospedale degli infermi di Biella, ItalyDipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Medicina Interna e del Trapianto di Fegato, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, ItalyLiver Unit, CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, ItalyDivision of Gastroenterology and Endoscopy, Fondazione IRCCS 'Casa Sollievo della Sofferenza', Viale Cappuccini, 71013 San Giovanni Rotondo, Foggia, ItalyDivision of Gastroenterology and Endoscopy, Fondazione IRCCS 'Casa Sollievo della Sofferenza', Viale Cappuccini, 71013 San Giovanni Rotondo, Foggia, ItalyHepatology Unit, Alessandro Manzoni Hospital, Lecco, ItalyHepatology Unit, Alessandro Manzoni Hospital, Lecco, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, 09100 Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, 09100 Cagliari, ItalyOspedale UO Medicina Interna, PO Barletta, ItalyInternal Medicine Unit, Santo Spirito Hospital Pescara, ItalyDepartment of Health Sciences, University Magna Graecia of Catanzaro, ItalyUOC Gastroenterologia Ospedale Valduce Como, ItalySC Gastroenterologia, ARNAS G.Brotzu, Ospedale San Michele, Cagliari, ItalyUniversità degli Studi di Perugia, Perugia, ItalyDivision of Medicine and Hepatology, Department of Clinical and Experimental Medicine, University Hospital of Messina, ItalySpedali Civili Gardone Val Trompia, Brescia, ItalySan Camillo Hospital, Rome, ItalyUniversity Hospital of Pisa, Pisa, ItalyUniversity Hospital of Pisa, Pisa, ItalyGastroenterology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, ItalyGastroenterology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, ItalyGastroenterology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, ItalyScientific Consultant, Scientific Institute for Research, Hospitalization and Healthcare, Negrar, Verona, Italy; Senior Scholar University of Padova, ItalyDepartment of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy; Gastroenterology Unit, Azienda Ospedale - Università Padova, Padova, Italy; RARE-LIVER ERN, ItalyDepartment of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy; Gastroenterology Unit, Azienda Ospedale - Università Padova, Padova, Italy; RARE-LIVER ERN, ItalyDepartment of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy; Gastroenterology Unit, Azienda Ospedale - Università Padova, Padova, Italy; RARE-LIVER ERN, ItalyGastroenterologia ed Endoscopia digestiva Azienda Ospedaliero-Universitaria di Ferrara, ItalyDIMEC Università di Bologna, IRCCS Policlinico di Sant'Orsola, Bologna, ItalyMedical Team Torino, Turin, ItalyUOSD Epatologia, Ospedale Umberto I°, ASP 8 Siracusa, ItalyUOSD Epatologia, Ospedale Umberto I°, ASP 8 Siracusa, ItalyValtellina e Alto Lario Hospital, Sondrio, ItalyOspedali Riuniti, Foggia, ItalySSD Epatologia AOU di Sassari, ItalyUOC Epatologia, Policlinico Universitario Tor Vergata, Rome, ItalyDepartment of Medicine, Surgery and Health Sciences, University of Trieste, Italy; Clinica Patologie del Fegato Azienda Sanitaria Universitaria Giuliano Isontina ASUGI, ItalySpedali Civili, Brescia, ItalySpedali Civili, Brescia, ItalyDepartment of Infectious Diseases and Emergency Infectious Diseases, D. Cotugno Hospital, Naples, ItalyGastroenterology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Veneto, ItalyGastroenterology and Hepatology Unit, Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialities, PROMISE, University of Palermo, ItalyDivision of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital, Monza, Italy; SC Epatologia e Gastroenterologia, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell’Ospedale Maggiore, 3, Italy; Corresponding authors. Addresses: Clinical Medicine and Hepatology Unit, Fondazione Policlinico Campus Bio-Medico of Rome, Via Alvaro del Portillo, 200, 00128 Rome, Italy. (U.V. Gentilucci), or University of Milano-Bicocca, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell’Ospedale Maggiore, 3, 20162, Milano, Italy; (M. Carbone).Unit of Clinical Medicine and Hepatology, Fondazione Policlinico Universitario Campus Bio-medico di Roma, Italy; Research Unit of Hepatology, Università Campus Bio-medico di Roma, Italy; Corresponding authors. Addresses: Clinical Medicine and Hepatology Unit, Fondazione Policlinico Campus Bio-Medico of Rome, Via Alvaro del Portillo, 200, 00128 Rome, Italy. (U.V. Gentilucci), or University of Milano-Bicocca, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell’Ospedale Maggiore, 3, 20162, Milano, Italy; (M. Carbone).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 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.http://www.sciencedirect.com/science/article/pii/S2589555925001260primary biliary cholangitisobeticholic acidreal-world evidencecirrhosisoverlap syndromeliver stiffness measurement |
| spellingShingle | 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 Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world JHEP Reports primary biliary cholangitis obeticholic acid real-world evidence cirrhosis overlap syndrome liver stiffness measurement |
| title | Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world |
| title_full | Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world |
| title_fullStr | Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world |
| title_full_unstemmed | Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world |
| title_short | Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world |
| title_sort | long term effectiveness safety and liver stiffness dynamics of pbc treatment with obeticholic acid in real world |
| topic | primary biliary cholangitis obeticholic acid real-world evidence cirrhosis overlap syndrome liver stiffness measurement |
| url | http://www.sciencedirect.com/science/article/pii/S2589555925001260 |
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