학술논문
Development and Validation of a Scoring System to Predict Response to Obeticholic Acid in Primary Biliary Cholangitis.
Document Type
Academic Journal
Author
De Vincentis A; Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy; Research Unit of Internal Medicine, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Roma, Italy.; Ampuero J; Hospital Universitario Virgen del Rocio, Seville, Spain.; Terracciani F; Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy; Research Unit of Hepatology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Roma, Italy.; D'Amato D; Gastroenterology Unit, Citta della salute e della scienza, Torino, Italy.; 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, San Gerardo Hospital, Monza, Italy.; 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, San Gerardo Hospital, Monza, Italy.; Cazzagon N; Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.; Bonaiuto E; Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.; Floreani A; Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.; Calvaruso V; Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Italy.; Cadamuro L; Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Italy.; Degasperi 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.; Morgando A; Gastroenterology Unit, Citta della salute e della scienza, Torino, Italy.; Vanni E; Gastroenterology Unit, Citta della salute e della scienza, Torino, Italy.; Lleo A; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy and IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.; Colapietro F; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy and IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.; Alvaro D; Department of Translational and Precision Medicine, University La Sapienza, Rome, Italy.; Castellaneta A; Gastroenterology Unit, Policlinico di Bari Hospital, Bari, Italy.; Labanca S; Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genova, Italy.; Viganò M; Hepatology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.; Distefano M; Department of Infectious Diseases, Umberto I Hospital, Siracusa, Italy.; Pace Palitti V; Hepatology Unit, Santo Spirito Hospital, Pescara, Italy.; Ricci C; Internal Medicine, Spedali Civili, Brescia, Italy.; De Matthaeis N; UOC of Gastroenterology, Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.; Marzioni M; Clinic of Gastroenterology and Hepatology, Universita Politecnica delle Marche, Ancona, Italy.; Gómez-Dominguez E; Hospital Universitario 12 de Octubre, Madrid, Spain.; Montero JL; Complexo Hospitalario Universitario Santiago de Compostela, Coruña, Spain.; Molina E; Hospital Universitario Reina Sofia, Cordoba, Spain.; Garcia-Buey L; Hospital Universitario de La Princesa, Madrid, Spain.; Casado M; Hospital de Torrecardenas, Almeria, Spain.; Berenguer M; Hospital Universitario La Fe, Valencia, Spain.; Conde I; Hospital Universitario La Fe, Valencia, Spain.; Simon MA; Hospital Universitario Lozano-Blesa, Zaragoza, Spain.; Fuentes J; Hospital Miguel Servet, Zaragoza, Spain.; Costa-Moreira P; Centro Hospitalar Sao Joao Porto, Portugal.; Macedo G; Centro Hospitalar Sao Joao Porto, Portugal.; Jorquera F; Complejo Asistencial Universitario de Leon, Spain.; Morillas RM; Hospital Germans Trias i Pujol, Badalona, Spain.; Presa J; Centro Hospitalar De Trás-Os-Montes E Alto Douro, Portugal.; Sousa JM; Hospital Universitario Virgen del Rocio, Seville, Spain.; Gomes D; Dept de Gastroenterología, Centro Hospitalar Universitário de Coimbra, Portugal.; Santos L; Dept de Gastroenterología, Centro Hospitalar Universitário de Coimbra, Portugal.; Olveira A; Hospital Universitario La Paz, Madrid, Spain.; Hernandez-Guerra M; Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Spain.; Aburruza L; Hospital Universitario de Donosti, Spain.; Santos A; Centro Hospitalar e Universitário de Coimbra, Portugal.; Carvalho A; Centro Hospitalar e Universitário de Coimbra, Portugal.; Uriz J; Complejo Hospitalario de Navarra, Spain.; Gutierrez ML; Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain.; Perez E; Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain.; Chessa L; Liver Unit, University Hospital of Cagliari, Cagliari, Italy.; Pellicelli A; Liver Unit, San Camillo Hospital, Rome, Italy.; Marignani M; Digestive and Liver Disease Department, School of Medicine and Psychology University Sapienza, Azienda Ospedaliera S. Andrea, Rome, Italy.; Muratori L; DIMEC Universita di Bologna, Policlinico di Sant'Orsola, Bologna, Italy.; Niro GA; Gastroenterology Unit, Fondazione Casa Sollievo Della Sofferenza IRCCS, San Giovanni Rotondo, Foggia, Italy.; Brunetto M; Hepatology Unit, University Hospital of Pisa, Pisa, Italy.; Ponziani FR; Internal Medicine and Hepatology Unit, Policlinico Gemelli, Sapienza University, Rome, Italy.; Pompili M; Internal Medicine and Hepatology Unit, Policlinico Gemelli, Sapienza University, Rome, Italy.; Marra F; Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.; Galli A; Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.; Mussetto A; Gastroenterology Unit, Santa Maria Delle Croci Hospital, Ravenna, Italy.; Alagna G; UOC Medicina Interna Ospedale SS. Annunziata Sassari, Italy.; Simone L; Department of Gastroenterology, University Hospital Sant'Anna, Ferrara, Italy.; Bertino G; Gastroenterology and Hepatology Unit, University Hospital Policlinico Vittorio Emanuele, Catania, Italy.; Rosina F; Medical Team Torino, Torino, Italy.; Cozzolongo R; Gastroenterology Unit, National Institute of Gastroenterology S de Bellis Research Hospital, Castellana Grotte, Italy.; Russello M; Liver Unit, Arnas Garibaldi, Catania, Italy.; Baiocchi L; Hepatology Unit, University of Rome 'Tor Vergata', Rome, Italy.; Saitta C; Division of Medicine and Hepatology, University Hospital of Messina 'Policlinico G. Martino', Messina, Italy.; Terreni N; Hepatology Unit, Valduce Hospital, Como, Italy.; Zolfino T; Department of Gastroenterology, Brotzu Hospital, Cagliari, Italy.; Rigamonti C; Dipartimento di Medicina Traslazionale, Università del Piemonte Orientale, Novara, Italy and Division of Internal Medicine, Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy.; Vigano R; Hepatology Unit, Niguarda Hospital, Milan, Italy.; Cuccorese G; Internal Medicine Ospedale 'R.Dimiccoli', Barletta, Italy.; Pozzoni P; Hepatology Unit, Alessandro Manzoni Hospital, Lecco, Italy.; Pedone C; Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy; Research Unit of Geriatrics, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Roma, Italy.; Grasso S; Research Unit of Electronics for Sensor Systems, Università Campus Bio-Medico di Roma, Roma, Italy.; Picardi A; Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy; Research Unit of Hepatology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Roma, Italy.; 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, San Gerardo Hospital, Monza, Italy.; Sacco R; Gastroenterology Unit, Ospedali Riuniti, Foggia, Italy.; Izzi A; Department of Infectious Diseases, D. Cotugno Hospital, Napoli, Italy.; Fernandez-Rodriguez C; Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain; University Rey Juan Carlos Alcorcón, Madrid, Spain.; Vespasiani-Gentilucci U; Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy; Research Unit of Hepatology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Roma, Italy. Electronic address: u.vespasiani@policlinicocampus.it.; 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, San Gerardo Hospital, Monza, Italy. Electronic address: marco.carbone@unimib.it.
Source
Publisher: W.B. Saunders for the American Gastroenterological Association Country of Publication: United States NLM ID: 101160775 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1542-7714 (Electronic) Linking ISSN: 15423565 NLM ISO Abbreviation: Clin Gastroenterol Hepatol Subsets: MEDLINE
Subject
Language
English
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 regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (alkaline phosphatase [ALP]/upper limit of normal [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, alanine aminotransferase [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 0.75, 0.78, and 0.72 for POISE, ALP/ULN<1.67, and NR response, which raised to 0.83, 0.88, and 0.81 with ORS+, respectively. The respective performances in validation were 0.70, 0.72, and 0.71 for ORS and 0.80, 0.84, and 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.
(Copyright © 2024. Published by Elsevier Inc.)
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 regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (alkaline phosphatase [ALP]/upper limit of normal [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, alanine aminotransferase [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 0.75, 0.78, and 0.72 for POISE, ALP/ULN<1.67, and NR response, which raised to 0.83, 0.88, and 0.81 with ORS+, respectively. The respective performances in validation were 0.70, 0.72, and 0.71 for ORS and 0.80, 0.84, and 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.
(Copyright © 2024. Published by Elsevier Inc.)