Author information

• ¹Division 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.
• ²Internal Medicine and Hepatology, University Campus Bio-Medico of Rome, Rome, Italy.
• ³Hepatology Unit, San Giuseppe Hospital, Milan, Italy.
• ⁴Department of Translational and Precision Medicine, University La Sapienza, Rome, Italy.
• ⁵Internal Medicine and Hepatology Unit, Policlinico Gemelli, Sapienza University, Rome, Italy.
• ⁶Clinic of Gastroenterology, San Martino Hospital, Genoa, Italy.
• ⁷Hepatology Unit, Santo Spirito Hospital, Pescara, Italy.
• ⁸Liver Unit, Arnas Garibaldi, Catania, Italy.
• ⁹IRCCS Sacro Cuore Institute Don Calabria, Gastroenterology, Negrar, Italy.
• ¹⁰Gastroenterology Unit, Spedali Civili Hospital, Brescia, Italy.
• ¹¹Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Italy.
• ¹²Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A.M. and A. Migliavacca" Center for Liver Disease, Milan, Italy.
• ¹³Internal Medicine and Hepatology, Humanitas Clinical and Research Center IRCCS, Humanitas University, Milan, Italy.
• ¹⁴Gastroenterology Unit, Policlinico di Bari Hospital, Bari, Italy.
• ¹⁵Liver Unit, San Camillo Hospital, Rome, Italy.
• ¹⁶Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.
• ¹⁷DIMEC Università di Bologna, Policlinico di Sant'Orsola, Via Massarenti 9, 40138, Bologna, Italy.
• ¹⁸Hepatology and Liver Transplant Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy.
• ¹⁹Gastroenterology Unit, Fondazione Casa Sollievo Della Sofferenza IRCCS, San Giovanni Rotondo, Foggia, Italy.
• ²⁰Gastroenterology Unit, Santa Maria Delle Croci Hospital, Ravenna, Italy.
• ²¹Gastroenterology Unit, National Institute of Gastroenterology "S de Bellis" Research Hospital, Castellana Grotte, Bari, Italy.
• ²²Hepatology Unit, Valduce Hospital, Como, Italy.
• ²³Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy.
• ²⁴Gastroenterology Unit, Città della salute e della scienza, Turin, Italy.
• ²⁵Hepatology Unit, Alessandro Manzoni Hospital, Lecco, Italy.
• ²⁶Hepatology Unit, University of Rome "Tor Vergata", Rome, Italy.
• ²⁷Liver Unit, University Hospital of Cagliari, Cagliari, Italy.
• ²⁸Medical Team Torino, Turin, Italy.
• ²⁹Gastroenterology and Hepatology Unit, University Hospital Policlinico Vittorio Emanuele, Catania, Italy.
• ³⁰Hepatology Unit, Niguarda Hospital, Milan, Italy.
• ³¹Department of Infectious Diseases, Umberto I Hospital, Syracuse, Italy.
• ³²Gastroenterology Unit, Ospedali Riuniti, Foggia, Italy.
• ³³Hepatology Unit, Santa Maria delle Grazie Hospital, Pozzuoli, Italy.
• ³⁴Hepatology Unit, Valtellina e Alto Lario Hospital, Sondrio, Italy.
• ³⁵Hepatology Unit, Treviglio Caravaggio Hospital, Treviglio, Italy.
• ³⁶Hepatology Unit, Spedali Civili Gardone Val Trompia, Brescia, Italy.
• ³⁷Gastroenterology Unit, Guido Salvini Hospital, Rho, Italy.
• ³⁸Oncology Unit, Istituto di Cura Città di Pavia, Pavia, Italy.
• ³⁹Hepatology Unit, Betania Hospital, Naples, Italy.
• ⁴⁰Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy.

Abstract

Background & aims: 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: 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 Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed.

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 Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%).

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: 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.