Journal Article

POS0857 EFFECTIVENESS AND SAFETY OF BIOLOGIC AND TARGET SYNTHETIC DRUGS FOR THE TREATMENT OF RHEUMATOID ARTHRITIS IN THE ERA OF JAK INHIBITORS: A REAL-LIFE STUDY FROM BIOPURE REGISTRY

Quarta, L., Lazzari, A., Mazzotta, D., Santo, L., Semeraro, A., Cantatore, F. P., Iannone, F., Marsico, A., Bucci, R. N. G., Carlino, G., Falappone, P. C. F., Serafino, L., Zuccaro, C., D’onofrio, F., Fornaro, M.

2023

Overview

BackgroundNowadays, rheumatoid arthritis (RA) patients can benefit from several drugs classified as biologic (b) or JAK inhibitors (JAKi). Four JAKi are now available, whose two JAKi, with predominantly JAK1 selectivity (JAK1i), came onto the market in 2020.ObjectivesThe aim of this study was to compare the effectiveness among RA patients included in BIOPURE registry on treatment on TNF inhibitors (TNFi) JAK1i, other JAKi (oJAKi), and other mechanisms of action (oMOA) bDMARD.MethodsData of RA patients who started a new line of treatment with a b/tsDMARD were prospectively collected from October 2020, when JAK1i was first prescribed, to May 2022. Demographics and disease characteristics were evaluated using standard descriptive statistics. Patients were divided in four groups: patients on TNFi therapy, patients on JAK1i (upadacitinib and filgotinib), patients on oJAKi (tofacitinib and baricitinib) and patients on oMOA (abatacept, tocilizumab and sarilumab). The drug survival was evaluated by Kaplan– Meier analysis. Estimated hazard ratios (HRs) of discontinuing therapy were assessed by multivariate regression models.ResultsSince October 2020, 580 RA patients started a new line treatment with b/tsDMARDs (171 TNFi, 192 oMOA, 88 oJAKi and 120 JAK1i). Overall cohort characteristics are reported in Table 1. As expected, monotherapy was more used in patients treated with JAK1i (73.6%), oJAKi (63.6%) and oMOA (54.7%) compared to TNFi (30.4%). Patients treated with JAK1i and oJAKi were more likely to be refractory to previous b/tsDMARDs, 76% of JAK1i and 76.2% of oJAKi had received prior treatment with ≥2 bDMARDs or other tsDMARDs. Patients treated with JAK1i presented higher disease activity compared to other b/tsDMARD and higher grade of disability at baseline compared to TNFi. Drug survival was similar between the four groups, being 66.7% for TNFi, 71.9% for oMOA, 64.8% for oJAKi and 69.8% for JAK1i (log-rank test:4.69, p=0.19) (Figure 1a). Multivariate cox regression model and K-M analysis (Figure 1b) showed that the main predictor of b/tsDMARDs discontinuation was a previous treatment with >2 b/tsDMARDs (HR: 1.85, 95% CI 1.21-2.85)Finally, a comparable number of adverse events causing drug discontinuation was observed: 10 (5.8%) in TNFi, 12 (6.3%) in oMOA, 9 (10.2%) in oJAKi and 10 (8.3%) in JAK1i.Table 1.Characteristics of RA patients treated with b/tsDMARDsVariablesTNFi (171 pt.)Other MOA (192 pt.) (84 ABA, 88 TCZ, 20 sarilumab)Prevalent JAK1i (129 pt.) (78 upadacitinib, 51 filgotinib)Other JAKi (88 pt.) (55 baricitinib, 33 tofacitinib)Age, mean (SD)56 (13)58 (12)55 (12)58 (11)Female, n(%)143 (83.6)156 (81.3)114 (88.4)71 (80.7)Seropositivity, n. (%)108 (74)123 (81.5)100 (90.9)*^50 (67.6)Erosive arthritis80 (46.8)99 (51.6)69 (53.5)48 (54.5)Comorbidities count, median (IQR)0 (0-1)1 (0-2)*1 (0-2)*0 (0-2)csDMARD, n. (%)119 (69.6)87 (45.3)*34 (26.4)*32 (36.4)*°Glucocorticoid, n. (%)99 (57.9)132 (68.8)87 (67.4)55 (62.5)Glucocorticoid dose daily, mean (SD)5.9 (3.3)6.2 (4.0)6.2 (3.9)5.5 (2.0)Biologic line, n. (%)12other99 (57.9)29 (17)43 (25.1)83 (43.2)*34 (17.7)75 (39.1)*31 (24)*°32 (24.8)66 (51.2)*21 (23.9)*°16 (18.2)51 (58)*°DAS28-ESR, mean (SD)4.2 (1.3)4.1 (1.5)4.5 (1.5)°^4 (1.2)CDAI, mean (SD)17 (10)18 (11)20 (12)^16 (8)VAS-pain, mean (SD)56 (25)53 (24)61 (25)57 (26)VAS-phGA, mean (SD)35 (18)41 (22)44 (22)*37 (22)VAS-pGA, mean (SD)56 (23)55 (24)61 (22)56 (21)HAQ-DI, mean (SD)1 (0.7)1.3 (0.8)*1.3 (0.7)*1.1 (0.8)phGA: physician global assessment; pGA: patient global assessment; VAS: visual analogue scale*p<0.05 vs TNFi; °p<0.05 vs other MOA, ^p<0.05 vs other JAKiConclusionOur study highlighted good effectiveness and safety of new and old b/tsDMARDs in Apulian cohort of RA patients included in BIOPURE registry. Of note, despite more than half patients starting JAK1i or oJAKi were multi-failure, they showed a similar drug survival compared to those on TNFi who were predominantly biologic-naïve.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier B.V,Elsevier Limited
• Subject: Comorbidity / Glucocorticoids / Janus kinase / Monoclonal antibodies / Registries / Regression analysis / Rheumatoid arthritis / Scientific Abstracts / Statistical analysis / Survival / Targeted synthetic drugs