Prediction of response to obeticholic acid in primary biliary cholangitis: Development and validation of the OCA response score (ORS). (March 2023)

• Record Type: Journal Article
• Authors: De Vincentis, A.; Terracciani, F.; D'Amato, D.; Invernizzi, P.; Morgando, A.; Vanni, E.; Viganò, M.; Alvaro, D.; Venere, R.; Lleo, A.; Colapietro, F.; Degasperi, E.; Viganò, R.; Giannini, E.G.; Labanca, S.; Feletti, V.; Mussetto, A.; Cozzolongo, R.; Losito, F.; Pompili, M.; Ponziani, F.R.; Niro, G.A.; Cotugno, R.; Pozzoni, P.; Chessa, L.; Cuccorese, G.; Palitti, V. Pace; Russello, M.; Cannavò, M.; Frazzetto, E.; Bertino, G.; Marzioni, M.; Terreni, N.; Zolfino, T.; Saitta, C.; Pellicelli, A.; Coco, B.; Brunetto, M.; Cazzagon, N.; Floreani, A.; Muratori, L.; Rosina, F.; Di Stefano, M.; Scifo, G.; Baiocchi, L.; Grassi, G.; Sacco, R.; Izzi, A.; Crocè, Saveria Lory; Fiorini, Cecilia; Marra, Fabio; Simone, Loredana; Morelli, Olivia; Abenavoli, L.; Pizzolante, F.; De Matthaeis, N.; Scaravaglio, M.; Gimignani, G.; Boano, V.; Manfredi, G.F.; Marignani, M.; Fanella, S.; Giacchetto, M.; Castellaneta, A.; Poggi, G.; Buzzanca, V.; Scivetti, P.; Tortora, A.; Casella, S.; Bellia, V.; Omazzi, B.F.; Alagna, G.; Ricci, C.; Poisa, P.; Rigamonti, C.; Calvaruso, V.; Vespasiani-Gentilucci, U.; Carbone, M.;
• Is Part Of: Digestive and liver disease. Volume 55(2023)Supplement 1
• Page Start: S4
• Page End: S5
• Publication Date: 2023-03
• Subjects: Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; 616.33005
• DOI: 10.1016/j.dld.2023.01.008
• Languages: English
• ISSNs: 1590-8658

Abstract

Abstract : Introduction: Obeticholic acid (OCA) is the approved second-line treatment for patients with primary biliary cholangitis (PBC). Biochemical response by POISE criteria is achieved in ∼40% of patients, according to registrative and post-marketing studies. Aim: To derive the OCA response score (ORS) for predicting response to OCA at 12 and 24 months, according to the POISE (alkaline phosphatase(ALP)/upper limit of normal(ULN) <1.67 with a reduction of at least 15%, and a normal bilirubin) and ALP/ULN<1.67 criteria. Materials and Methods: We used the Italian RECAPITULATE database including centers from Italian PBC Registry, the Sicilian PBC Network, the PBC Project Piemonte-Liguria-Valle D'Aosta and CLEO/AIGO PBC study group. Multivariable Cox's regressions with backward selection method were applied to obtain parsimonious predictive models, including pre-treatment variables and/or the change of ALP/ULN and total bilirubin after 6 months' therapy. Discrimination and calibration were evaluated by c-statistics and comparing observed and predicted probabilities, and internally validated with bootstrap resampling procedure. Results: 441 PBC patients (median age 58, women 88%, cirrhosis 34%, median follow-up 24 months) with at least 6 months' observation after of OCA prescription, were included for ORS derivation. The observed 12 and 24 months' response probabilities were 38%, 47% for POISE and 58%, 67% for ALP/ULN<1.67 criteria. A score including age, pre-treatment pruritus, cirrhosis, ALP/ULN, GGT/ULN and bilirubin (ORS), and one that includes also the relative change of ALP/ULN and total bilirubin after 6 months (ORS+), showed good discrimination for response by POISE (c-statistics=0.76 and 0.84, for ORS and ORS+, respectively) and by ALP/ULN<1.67 (c-statistics=0.78 and 0.89, for ORS and ORS+, respectively). Bootstrap validation evidenced modest overfitting (slopes>0.90) and consistent discriminative performance. Mean absolute errors <0.04 were observed for prediction of POISE and ALP/ULN<1.67 response at 24 months according to ORS and ORS+. Conclusions: The ORS accurately predicts OCA response at 12 and 24 months. This will enable to enhance allocation of second-line therapies in PBC with a personalised medicine approach.