作者
Antonio De Vincentis,Javier Ampuero,Francesca Terracciani,Daphne D’Amato,Alessio Gerussi,Laura Cristoferi,Nora Cazzagon,Emanuela Bonaiuto,Annarosa Floreani,V. Calvaruso,Luca Cadamuro,Elisabetta Degasperi,Anna Morgando,Ester Vanni,Ana Lleó,Francesca Colapietro,Domenico Alvaro,A. Castellaneta,Sara Labanca,Mauro Viganò,Marco Distefano,Valeria Pace Palitti,Chiara Ricci,Nicoletta De Matthaeis,Marco Marzioni,Elena Gómez-Domínguez,José-Luis Montero,Esther Molina,Luisa Garcı́a-Buey,Marta Casado,Marina Berenguer,Isabel Conde,Miguel Ángel Simón,Javier Fuentes,Pedro Costa‐Moreira,Guilherme Macedo,Francisco Jorquera,Rosa-Maria Morillas,José Presa,Jose-Manuel Sousa,Dário Gomes,Luís C. Santos,Antonio Olveira,Manuel Hernández‐Guerra,Leire Aburruza,Arsénio Santos,Armando Carvalho,Juan Uríz,Maria-Luisa Gutierrez,Elia Pérez,Luchino Chessa,Adriano Pellicelli,Massimo Marignani,Luigi Muratori,Grazia Anna Niro,Maurizia Rossana Brunetto,Francesca Romana Ponziani,Maurizio Pompili,Fabio Marra,Andrea Galli,Alessandro Mussetto,Giuliano Alagna,Loredana Simone,Gaetano Bertino,F. Rosina,Raffaele Cozzolongo,Maurizio Russello,Leonardo Baiocchi,Carlo Saitta,N. Terreni,Teresa Zolfino,Cristina Rigamonti,Raffaella Viganò,Giuseppe Cuccorese,Pietro Pozzoni,Claudio Pedone,Simone Grasso,Antonio Picardi,Pietro Invernizzi,Rodolfo Sacco,Antonio Izzi,Conrado Fernández‐Rodríguez,Umberto Vespasiani‐Gentilucci,Marco Carbone,Miki Scaravaglio,Eugenia Nofit,Paolo Gallo,Giovanni Galati,Francesco Pezzato,Paolo Rollo,Erica D’Ovidio,B. Coco,A. Tortora,Cecília F. Fiorini,Rosanna Venere,Gaetano Scifo,Mariarita Cannavò,Valentina Feletti,Fabrizio Pizzolante,Edoardo G. Giannini,Rosa Cotugno,Silvia Fanella,Francesco Losito,G Grassi,Giulia Francesca Manfredi,Valerio Buzzanca,Barbara Omazzi,Silvia Casella,Francesca Zani,Chiara Ricci,Valentina Bellia,Ludovico Abenavoli,Olivia Morelli,Lory Saveria Crocè,Paolo Scivetti,Antonio Panero,Valentina Boano,Guido Poggi,Giancarlo Gimignani,Alessandro Conforti,Evelise Frazzetto,Laura Rapisarda,Shrin Demma
摘要
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.