JHEP Reports (Apr 2021)

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

  • Daphne D’Amato,
  • Antonio De Vincentis,
  • Federica Malinverno,
  • Mauro Viganò,
  • Domenico Alvaro,
  • Maurizio Pompili,
  • Antonino Picciotto,
  • Valeria Pace Palitti,
  • Maurizio Russello,
  • Silvia Storato,
  • Marie Graciella Pigozzi,
  • Vincenza Calvaruso,
  • Elisabetta De Gasperi,
  • Ana Lleo,
  • Antonino Castellaneta,
  • Adriano Pellicelli,
  • Nora Cazzagon,
  • Annarosa Floreani,
  • Luigi Muratori,
  • Stefano Fagiuoli,
  • Grazia Anna Niro,
  • Valentina Feletti,
  • Raffaele Cozzolongo,
  • Natalia Terreni,
  • Marco Marzioni,
  • Rinaldo Pellicano,
  • Pietro Pozzoni,
  • Leonardo Baiocchi,
  • Luchino Chessa,
  • Floriano Rosina,
  • Gaetano Bertino,
  • Maria Vinci,
  • Anna Morgando,
  • Ester Vanni,
  • Gaetano Scifo,
  • Rodolfo Sacco,
  • Maria D’Antò,
  • Valentina Bellia,
  • Roberto Boldizzoni,
  • Silvia Casella,
  • Barbara Omazzi,
  • Guido Poggi,
  • Laura Cristoferi,
  • Alessio Gerussi,
  • Vincenzo Ronca,
  • Rosanna Venere,
  • Francesca Ponziani,
  • Maria Cannavò,
  • Alessandro Mussetto,
  • Rosanna Fontana,
  • Francesco Losito,
  • Evelise Frazzetto,
  • Marco Distefano,
  • Francesca Colapietro,
  • Sara Labanca,
  • Giulia Marconi,
  • Giuseppe Grassi,
  • Giovanni Galati,
  • Sarah Elizabeth O’Donnell,
  • Clara Mancuso,
  • Giacomo Mulinacci,
  • Andrea Palermo,
  • Ernesto Claar,
  • Antonio Izzi,
  • Antonio Picardi,
  • Pietro Invernizzi,
  • Marco Carbone,
  • Umberto Vespasiani-Gentilucci

Journal volume & issue
Vol. 3, no. 2
p. 100248

Abstract

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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.

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