Real-world experience with obeticholic acid in patients with primary biliary cholangitis.

AIH, autoimmune hepatitis ALP, alkaline phosphatase ALT, alanine transferase AMA, antimitochondrial antibodies ANA, antinuclear antibodies AST, aspartate transferase Autoimmunity CRFs, case record forms Cholestasis Cirrhosis EDC, electronic data capture GGT, gamma-glutamyl transferase OC, Overall cohort OCA, obeticholic acid Overlap PBC-AIH PBC, primary biliary cholangitis QC, quality control RCT, randomised controlled trial RR, risk ratio TCC, Treatment Completer Cohort TIPS, transjugular intrahepatic portosystemic shunt UDCA, ursodeoxycholic acid ULN, upper limit of normal aRR, adjusted risk ratio

Journal

JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237

Informations de publication

Date de publication:
Apr 2021
Historique:
received: 10 09 2020
revised: 23 11 2020
accepted: 06 01 2021
entrez: 8 3 2021
pubmed: 9 3 2021
medline: 9 3 2021
Statut: epublish

Résumé

Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.

Sections du résumé

BACKGROUND & AIMS OBJECTIVE
Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions.
METHODS METHODS
Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to
RESULTS RESULTS
We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to
CONCLUSIONS CONCLUSIONS
Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC.
LAY SUMMARY BACKGROUND
Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.

Identifiants

pubmed: 33681748
doi: 10.1016/j.jhepr.2021.100248
pii: S2589-5559(21)00024-0
pmc: PMC7930359
doi:

Types de publication

Journal Article

Langues

eng

Pagination

100248

Informations de copyright

© 2021 The Author(s).

Déclaration de conflit d'intérêts

The authors have no conflicts of interest to declare related to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

Références

J Hepatol. 2006 Feb;44(2):400-6
pubmed: 16356577
Aliment Pharmacol Ther. 2020 Jan;51(1):192-193
pubmed: 31850571
Am J Gastroenterol. 2020 Jul;115(7):1066-1074
pubmed: 32618657
N Engl J Med. 2018 Jun 07;378(23):2171-2181
pubmed: 29874528
Lancet Gastroenterol Hepatol. 2018 Sep;3(9):626-634
pubmed: 30017646
J Hepatol. 2017 Jul;67(1):145-172
pubmed: 28427765
Gastroenterology. 2015 Dec;149(7):1804-1812.e4
pubmed: 26261009
Gastroenterology. 2009 Apr;136(4):1281-7
pubmed: 19208346
Hepatol Commun. 2020 Jul 06;4(9):1332-1345
pubmed: 32923836
Am J Epidemiol. 2004 Apr 1;159(7):702-6
pubmed: 15033648
Scand J Gastroenterol. 2019 Oct;54(10):1274-1282
pubmed: 31564176
N Engl J Med. 1994 May 12;330(19):1342-7
pubmed: 8152446
Hepatology. 2016 Mar;63(3):930-50
pubmed: 26223498
Gastroenterology. 2006 Mar;130(3):715-20
pubmed: 16530513
N Engl J Med. 2016 Aug 18;375(7):631-43
pubmed: 27532829
Lancet. 2015 Oct 17;386(10003):1565-75
pubmed: 26364546
J Autoimmun. 2018 Dec;95:171-178
pubmed: 30420264
J Hepatol. 2011 Dec;55(6):1361-7
pubmed: 21703194
Hepatology. 2008 Sep;48(3):871-7
pubmed: 18752324
Am J Gastroenterol. 2010 Oct;105(10):2186-94
pubmed: 20502446
Lancet Gastroenterol Hepatol. 2019 Jun;4(6):445-453
pubmed: 30922873
Ann Hepatol. 2020 Jan - Feb;19(1):5-16
pubmed: 31771820
Gastroenterology. 2013 Mar;144(3):560-569.e7; quiz e13-4
pubmed: 23246637

Auteurs

Daphne D'Amato (D)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Antonio De Vincentis (A)

Internal Medicine and Hepatology, University Campus Bio-Medico of Rome, Rome, Italy.

Federica Malinverno (F)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Mauro Viganò (M)

Hepatology Unit, San Giuseppe Hospital, Milan, Italy.

Domenico Alvaro (D)

Department of Translational and Precision Medicine, University La Sapienza, Rome, Italy.

Maurizio Pompili (M)

Internal Medicine and Hepatology Unit, Policlinico Gemelli, Sapienza University, Rome, Italy.

Antonino Picciotto (A)

Clinic of Gastroenterology, San Martino Hospital, Genoa, Italy.

Valeria Pace Palitti (VP)

Hepatology Unit, Santo Spirito Hospital, Pescara, Italy.

Maurizio Russello (M)

Liver Unit, Arnas Garibaldi, Catania, Italy.

Silvia Storato (S)

IRCCS Sacro Cuore Institute Don Calabria, Gastroenterology, Negrar, Italy.

Marie Graciella Pigozzi (MG)

Gastroenterology Unit, Spedali Civili Hospital, Brescia, Italy.

Vincenza Calvaruso (V)

Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Italy.

Elisabetta De Gasperi (E)

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A.M. and A. Migliavacca" Center for Liver Disease, Milan, Italy.

Ana Lleo (A)

Internal Medicine and Hepatology, Humanitas Clinical and Research Center IRCCS, Humanitas University, Milan, Italy.

Antonino Castellaneta (A)

Gastroenterology Unit, Policlinico di Bari Hospital, Bari, Italy.

Adriano Pellicelli (A)

Liver Unit, San Camillo Hospital, Rome, Italy.

Nora Cazzagon (N)

Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.

Annarosa Floreani (A)

Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.

Luigi Muratori (L)

DIMEC Università di Bologna, Policlinico di Sant'Orsola, Via Massarenti 9, 40138, Bologna, Italy.

Stefano Fagiuoli (S)

Hepatology and Liver Transplant Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy.

Grazia Anna Niro (GA)

Gastroenterology Unit, Fondazione Casa Sollievo Della Sofferenza IRCCS, San Giovanni Rotondo, Foggia, Italy.

Valentina Feletti (V)

Gastroenterology Unit, Santa Maria Delle Croci Hospital, Ravenna, Italy.

Raffaele Cozzolongo (R)

Gastroenterology Unit, National Institute of Gastroenterology "S de Bellis" Research Hospital, Castellana Grotte, Bari, Italy.

Natalia Terreni (N)

Hepatology Unit, Valduce Hospital, Como, Italy.

Marco Marzioni (M)

Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy.

Rinaldo Pellicano (R)

Gastroenterology Unit, Città della salute e della scienza, Turin, Italy.

Pietro Pozzoni (P)

Hepatology Unit, Alessandro Manzoni Hospital, Lecco, Italy.

Leonardo Baiocchi (L)

Hepatology Unit, University of Rome "Tor Vergata", Rome, Italy.

Luchino Chessa (L)

Liver Unit, University Hospital of Cagliari, Cagliari, Italy.

Floriano Rosina (F)

Medical Team Torino, Turin, Italy.

Gaetano Bertino (G)

Gastroenterology and Hepatology Unit, University Hospital Policlinico Vittorio Emanuele, Catania, Italy.

Maria Vinci (M)

Hepatology Unit, Niguarda Hospital, Milan, Italy.

Anna Morgando (A)

Gastroenterology Unit, Città della salute e della scienza, Turin, Italy.

Ester Vanni (E)

Gastroenterology Unit, Città della salute e della scienza, Turin, Italy.

Gaetano Scifo (G)

Department of Infectious Diseases, Umberto I Hospital, Syracuse, Italy.

Rodolfo Sacco (R)

Gastroenterology Unit, Ospedali Riuniti, Foggia, Italy.

Maria D'Antò (M)

Hepatology Unit, Santa Maria delle Grazie Hospital, Pozzuoli, Italy.

Valentina Bellia (V)

Hepatology Unit, Valtellina e Alto Lario Hospital, Sondrio, Italy.

Roberto Boldizzoni (R)

Hepatology Unit, Treviglio Caravaggio Hospital, Treviglio, Italy.

Silvia Casella (S)

Hepatology Unit, Spedali Civili Gardone Val Trompia, Brescia, Italy.

Barbara Omazzi (B)

Gastroenterology Unit, Guido Salvini Hospital, Rho, Italy.

Guido Poggi (G)

Oncology Unit, Istituto di Cura Città di Pavia, Pavia, Italy.

Laura Cristoferi (L)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Alessio Gerussi (A)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Vincenzo Ronca (V)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Rosanna Venere (R)

Department of Translational and Precision Medicine, University La Sapienza, Rome, Italy.

Francesca Ponziani (F)

Internal Medicine and Hepatology Unit, Policlinico Gemelli, Sapienza University, Rome, Italy.

Maria Cannavò (M)

Liver Unit, Arnas Garibaldi, Catania, Italy.

Alessandro Mussetto (A)

Gastroenterology Unit, Santa Maria Delle Croci Hospital, Ravenna, Italy.

Rosanna Fontana (R)

Gastroenterology Unit, Fondazione Casa Sollievo Della Sofferenza IRCCS, San Giovanni Rotondo, Foggia, Italy.

Francesco Losito (F)

Gastroenterology Unit, National Institute of Gastroenterology "S de Bellis" Research Hospital, Castellana Grotte, Bari, Italy.

Evelise Frazzetto (E)

Gastroenterology and Hepatology Unit, University Hospital Policlinico Vittorio Emanuele, Catania, Italy.

Marco Distefano (M)

Department of Infectious Diseases, Umberto I Hospital, Syracuse, Italy.

Francesca Colapietro (F)

Internal Medicine and Hepatology, Humanitas Clinical and Research Center IRCCS, Humanitas University, Milan, Italy.

Sara Labanca (S)

Clinic of Gastroenterology, San Martino Hospital, Genoa, Italy.

Giulia Marconi (G)

Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy.

Giuseppe Grassi (G)

Hepatology Unit, University of Rome "Tor Vergata", Rome, Italy.

Giovanni Galati (G)

Internal Medicine and Hepatology, University Campus Bio-Medico of Rome, Rome, Italy.

Sarah Elizabeth O'Donnell (SE)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Clara Mancuso (C)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Giacomo Mulinacci (G)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Andrea Palermo (A)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Ernesto Claar (E)

Hepatology Unit, Betania Hospital, Naples, Italy.

Antonio Izzi (A)

Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy.

Antonio Picardi (A)

Internal Medicine and Hepatology, University Campus Bio-Medico of Rome, Rome, Italy.

Pietro Invernizzi (P)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Marco Carbone (M)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Umberto Vespasiani-Gentilucci (U)

Internal Medicine and Hepatology, University Campus Bio-Medico of Rome, Rome, Italy.

Classifications MeSH