Author information

¹Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy; Research Unit of Internal Medicine, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy.

²Hospital Universitario Virgen del Rocio, Seville, Spain.

³Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy; Research Unit of Hepatology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy.

⁴Gastroenterology Unit, Citta della salute e della scienza, Torino, Italy.

⁵Division 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.

⁶Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.

⁷Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Italy.

⁸Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC A.M. and A. Migliavacca Center for Liver Disease, Milan, Italy.

⁹Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy and IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

¹⁰Department of Translational and Precision Medicine, University La Sapienza, Rome, Italy.

¹¹Gastroenterology Unit, Policlinico di Bari Hospital, Bari, Italy.

¹²Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino.

¹³Hepatology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.

¹⁴Department of Infectious Diseases, Umberto I Hospital, Siracusa, Italy.

¹⁵Hepatology Unit, Santo Spirito Hospital, Pescara, Italy.

¹⁶Internal Medicine, Spedali Civili, Brescia, Italy.

¹⁷UOC of Gastroenterology, Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences Department, Fondazione Policlinico Universitario A.Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

¹⁸Clinic of Gastroenterology and Hepatology, Universita Politecnica delle Marche, Ancona, Italy.

¹⁹Hospital Universitario 12 de Octubre, Madrid, Spain.

²⁰Complexo Hospitalario Universitario Santiago de Compostela, Coruña, Spain.

²¹Hospital Universitario Reina Sofia, Cordoba, Spain.

²²Hospital Universitario de La Princesa, Madrid, Spain.

²³Hospital de Torrecardenas, Almeria, Spain.

²⁴Hospital Universitario La Fe, Valencia, Spain.

²⁵Hospital Universitario Lozano-Blesa, Zaragoza, Spain.

²⁶Hospital Miguel Servet, Zaragoza, Spain.

²⁷Centro Hospitalar Sao Joao Porto, Portugal.

²⁸Complejo Asistencial Universitario de Leon, Spain.

²⁹Hospital Germans Trias i Pujol, Badalona, Spain.

³⁰Centro Hospitalar De Trás-Os-Montes E Alto Douro, Portugal.

³¹Dept de Gastroenterología, Centro Hospitalar Universitário de Coimbra, Portugal.

³²Hospital Universitario La Paz, Madrid, Spain.

³³Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Spain.

³⁴Hospital Universitario de Donosti, Spain.

³⁵Centro Hospitalar e Universitário de Coimbra, Portugal.

³⁶Complejo Hospitalario de Navarra, Spain.

³⁷Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain.

³⁸Liver Unit, University Hospital of Cagliari, Cagliari, Italy.

³⁹Liver Unit, San Camillo Hospital, Rome, Italy.

⁴⁰Digestive and Liver Disease Department, School of Medicine and Psychology University Sapienza, Azienda Ospedaliera S. Andrea, Rome, Italy.

⁴¹DIMEC Universita di Bologna, Policlinico di Sant'Orsola, Bologna, Italy.

⁴²Gastroenterology Unit, Fondazione Casa Sollievo Della Sofferenza IRCCS, San Giovanni Rotondo, Foggia, Italy.

⁴³University Hospital of Pisa, Pisa, Italy, Hepatology Unit.

⁴⁴Internal Medicine and Hepatology Unit, Policlinico Gemelli, Sapienza University, Rome, Italy.

⁴⁵Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.

⁴⁶Gastroenterology Unit, Santa Maria Delle Croci Hospital, Ravenna, Italy.

⁴⁷UOC Medicina Interna Ospedale SS. Annunziata Sassari.

⁴⁸Department of Gastroenterology, University Hospital Sant'Anna, Ferrara, Italy.

⁴⁹Gastroenterology and Hepatology Unit, University Hospital Policlinico Vittorio Emanuele, Catania, Italy.

⁵⁰Medical Team Torino, Torino, Italy.

⁵¹Gastroenterology Unit, National Institute of Gastroenterology S de Bellis Research Hospital, Castellana Grotte, Italy.

⁵²Liver Unit, Arnas Garibaldi, Catania, Italy.

⁵³Hepatology Unit, University of Rome "Tor Vergata", Rome, Italy.

⁵⁴Division of Medicine and Hepatology, University Hospital of Messina "Policlinico G. Martino", Messina, Italy.

⁵⁵Hepatology Unit, Valduce Hospital, Como, Italy.

⁵⁶Department of Gastroenterology, Brotzu Hospital, Cagliari, Italy.

⁵⁷Dipartimento di Medicina Traslazionale, Università del Piemonte Orientale, Novara, Italy and Division of Internal Medicine, Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy.

⁵⁸Hepatology Unit, Niguarda Hospital, Milan, Italy.

⁵⁹Internal Medicine Ospedale "R.Dimiccoli", Barletta, Italy.

⁶⁰Hepatology Unit, Alessandro Manzoni Hospital, Lecco, Italy.

⁶¹Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy; Research Unit of Geriatrics, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy.

⁶²Research Unit of Electronics for Sensor Systems, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy.

⁶³Gastroenterology Unit, Ospedali Riuniti, Foggia, Italy.

⁶⁴Department of Infectious Diseases, D. Cotugno Hospital, Napoli, Italy.

⁶⁵Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain; University Rey Juan Carlos Alcorcón, Madrid, Spain.

⁶⁶Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy; Research Unit of Hepatology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy. Electronic address: u.vespasiani@policlinicocampus.it.

⁶⁷Division 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. Electronic address: marco.carbone@unimib.it.

Abstract

Background & aims: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA.

Methods: We used data from the Italian RECAPITULATE (N 441) and the IBER-PBC (N 244) OCA real-world prospective cohorts to derive/validate a score including widely available variables obtained either pre-treatment (ORS), or also after 6 months of treatment (ORS+). Multivariable Cox's regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (ALP/ULN<1.67 with a reduction of at least 15%, and normal bilirubin), or ALP/ULN<1.67, or NORMAL RANGE criteria (NR: normal ALP, ALT and bilirubin) up to 24 months.

Results: Depending on the response criteria, ORS included age, pruritus, cirrhosis, ALP/ULN, ALT/ULN, GGT/ULN and bilirubin. ORS+ also included ALP/ULN and bilirubin after 6 months of OCA therapy. Internally validated c-statistics for ORS were of 0.75, 0.78 and 0.72 for POISE, ALP/ULN<1.67 and NR response, which raised to 0.83, 0.88, 0.81 with ORS+, respectively. The respective performances in validation were of 0.70, 0.72 and 0.71 for ORS, and 0.80, 0.84, 0.78 for ORS+. Results were consistent across groups with mild/severe disease.

Conclusions: We developed and externally validated a scoring system capable to predict OCA response according to different criteria. This tool will enhance a stratified second-line therapy model to streamline standard care and trial delivery in PBC.