Ab0302 discontinuation Rate and Predictors of Jaki Discontinuation in a Real Life Cohort: Results From a Multicentric Italian Study on 864 Patients With Ra

Abstract

BackgroundThe recent EULAR recommendations [1,2] suggest using JAK-inhibitors (JAKis) for treating RA patients. These drugs include both selective (upadactinib and filgotinib) and unselective (tofacitinib and baricitinib) JAKis.ObjectivesTo describe JAKis’ discontinuation rate and to determine predictors of JAKIs’ discontinuation in a real life setting.MethodsAll patients with RA treated with JAKis were prospectively followed up for at least 12 months in this multicentric study carried out on 23 Italian centres. For each patient, the following variables were collected: sex, age, disease duration, smoking, BMI, comorbidities (diabetes, hypertension, hypercholesterolemia, cancer, major cardiovascular events), positive RF/ACPA, cDMARDs at baseline, prednisone at baseline, previous use of JAKis, discontinuation, time to discontinuation, JAKis line of treatment, DAS28-ESR at baseline, 6 and 12 months. Statistical analyses were performed using R (2022.12.0).Results864 patients were included (Table 1). 487 (55.2%) received baricitinib, 213 (24.6%) tofacitinib, 111 (12.8%) upadacitinib and 62 (7.2%) filgotinib. 192 (22.2%) patients discontinued JAKis after a median time of 334 days (IQR 154.5-879.5). Among them, a statistical difference was found between selective-JAKis and other JAKis (p=0.03, 14.6% of selective JAKis vs 85.4% of other JAKis); finally unselective JAKis were discontinued later than selective JAKis (p<0.001, median 401.5 days, IQR 197.5-976 for unselective JAKis vs median 74 days, IQR 129-212 for selective JAKis). Discontinuation’s causes are reported inFigure 1. Notably, VZV infection determined JAKis withdrawal in 4 patients and pulmonary embolism/deep venous thrombosis in 6 patients (both with baricitinib). Regarding discontinuations’ causes, no differences between selective JAKis and other JAKis were found with factor logistic regression model. At multivariate analysis, predictors of discontinuation were prednisone at baseline (OR 1.48, p=0.03), treatment with unselective JAKis (OR 1.79, p=0.01), and line of treatment (OR 1.29 p<0.001).ConclusionOur study showed that only a minority of patients discontinued JAKis. Among discontinuation‘s causes, no differences between selective JAKis and other JAKis were found. Predictors of JAKis discontinuation were prednisone at baseline, treatment with unselective JAKis and line of treatment (with more advanced lines of treatment associated with a higher risk of discontinuation).References[1] Smolen JS, et al. Ann Rheum Dis 2020.[2] Smolen JS, et al. Ann Rheum Dis 2023.Table 1.General features of 864 RA patientsVariableN (%)Mean age at baseline (SD) (N=863)58.79 (12.84)Females678 (78.47)Mean BMI (Kg/cm2) at baseline (SD) (N=626)25.19 (3.79)Smoking (N=799)Yes151 (18.89)No504 (63.01)Former144 (18.02)Positive RF (N=809)533 (65.88)Positive ACPA (N=796)498 (61.56)Diabetes (N=770)70 (9.09)Hypertension (N=771)302 (39.17)Hypercholesterolemia (N=769)196 (25.49)Previous MACE (N=768)47 (6.12)Previous cancer (N=770)42 (5.45)Disease duration (months), (median, IQR) (N=855)77 (30-157)Mean DAS28-ESR at baseline (SD) (N=746)5.29 (1.06)cDMARDs at baseline (N=781)287 (36.75)PDN at baseline (N=780)444 (56.92)Median dosage (IQR) of PDN (mg/day)5.00 (4.00-5.00)JAKis naïve (N=853)731 (85.70)Line of JAKis treatment 1^247 (26.59) 2^211 (24.42) 3^181 (20.64) 4^111 (12.84) 5^65 (7.52) 6^29 (3.35) 7^12 (1.39) 8^3 (0.35) 9^2 (0.23) 10^3 (0.35)Patients who discontinued JAKis192 (22.2)Time to discontinuation (days), (median, IQR) (N=863)334 (154.5-879.5)Legends to Table 1:RA: rheumatoid arthritis; SD: standard deviation; BMI: Body Mass Index; RF: Rheumatoid Factor; ACPA: Autoantibodies against citrullinated peptides/proteins; MACE: Major cardiovascular events; PDN: prednisone; IQR: interquartile range; DAS28-ESR: Disease Activity Score-28 for Rheumatoid Arthritis with ESR; cDMARDs: conventional Disease-modifying antirheumatic agents; JAKis: JAK inhibitors.Acknowledgements:NIL.Disclosure of InterestsMaddalena Larosa: None declared, Alarico Ariani: None declared, Dario Camellino Speakers bureau: Abiogen, GSK, Paid instructor for: Mylan, Andrea Becciolini: None declared, Gerolamo Bianchi: None declared, Eleonora Di Donato: None declared, Giuditta Adorni: None declared, Daniele Santilli: None declared, Gianluca Lucchini: None declared, Massimo Reta: None declared, Olga Addimanda: None declared, Alberto Lo Gullo: None declared, elisa visalli: None declared, Rosario Foti: None declared, Giorgio Amato: None declared, Francesco De Lucia: None declared, antonella farina: None declared, Francesco Girelli: None declared, Simone Bernardi: None declared, Giulio Ferrero: None declared, Romina Andracco: None declared, Marino Paroli: None declared, Natalia Mansueto: None declared, rosalba caccavale: None declared, Patrizia Del Medico: None declared, Aldo Molica Colella: None declared, Veronica Franchina: None declared, Francesco Molica Colella: None declared, Federica Lumetti: None declared, Gilda Sandri: None declared, Carlo Salvarani: None declared, Marta Priora: None declared, Aurora Ianniello: None declared, Valeria Nucera: None declared, Francesca Ometto: None declared, Ilaria Platé: None declared, eugenio arrigoni: None declared, Alessandra Bezzi: None declared, Maria Cristina Focherini: None declared, Fabio Mascella: None declared, Vincenzo Bruzzese: None declared, Palma Scolieri: None declared, Simone Parisi: None declared, Maria Chiara Ditto: None declared, Enrico Fusaro: None declared, Viviana Ravagnani: None declared, Rosetta Vitetta: None declared, Alessia Fiorenza: None declared, Guido Rovera: None declared, Alessandro Volpe: None declared, Antonio Marchetta: None declared, Matteo Colina: None declared, Elena Bravi: None declared.