AB0388 COMPARATIVE EFFECTIVENESS OF RITUXIMAB, TOCILIZUMAB AND TNFI BIOLOGICS IN RHEUMATOID ARTHRITIS PATIENTS. INFLUENCE OF CLINICAL AND INFLAMMATORY PROFILES

Abstract

Objectives 1) To compare the real-world effectiveness among RA patients starting 3 biologic DMARDs (bDMARDs). 2) To evaluate whether patients’ clinical characteristics influence the response to specific bDMARDs. 3) To analyze the impact of bDMARDs on inflammatory profiles. Methods Eighty RA patients initiating TNFi, 22 patients treated with TCZ and 28 treated with RTX, the last ones after switching from TNFi and given as second bDMARDs, were included in the study. Effectiveness was assessed before and after 3 and 6 months of treatment by the European League Against Rheumatism (EULAR) criteria. Adjusted differences were estimated with multivariable linear regression. Differences in treatment outcomes were calculated as a function of patients’ characteristics, through regression modelling. Extensive analysis of the inflammatory profile using a multiplex were also performed. Results A high proportion of patients starting TNFi showed early EULAR Good Response (65,8% responders at 3 months). After 6 months of therapy this percentage even increased (70,6%), so that tender joints’ counts, swollen joints count, SDAI and HAQ improved significantly. After switching from a first TNFi, RTX treatment promoted better early response (81,8% responders after 3 months) than TCZ (67% responders). Differences remained significant after adjusting for potential confounders. Yet, after 6 months, efficacy was similar among both non-TNFi DMARDs, even improving the effectiveness in TCZ-treated RA patients based on EULAR response rate (DAS28 change: 5.09±1.4 to 2.7±1,17) vs RTX-treated patients (DAS28 change: 4.8±1.3 to 3-1±1.3). Patients older, and those suffering arterial hypertension (AH) or hyperlipidemia showed less effectiveness for both, TNFi and non-TNFi DMARDs, most remarkable for RTX and after 6 months of treatment. Analysis of the inflammatory profile, by evaluating 27 key biomarkers of inflammation, showed, in patients’ responders to therapy, specific profiles depending on the biologic DMARD administered. Thus, after 6 months of RTX, a generalized reduction in the expression levels of 22/27 proteins evaluated was observed, while TCZ mainly inhibited proteins involved in cell maturation, proliferation and leukocytes recruitment (IL6, GCSF, IP-10, IFNγ, RANTES). On the other hand, TNFi mainly reduced molecules related to leukocytes’ recruitment (IL-2, IL-8, MIP1β, RANTES). Conclusion 1) Treatment outcomes among RA patients treated with non-TNFi bDMARDs in standard clinical practice, are in line with a superior early effectiveness of RTX compared with TCZ. However, effectiveness in TCZ-treated RA patients increases after 6 months of treatment vs RTX. 2) Patients characteristics influence the response to bDMARDs, suggesting the need of evaluating the benefit risk/ratio based on a personalized clinical evaluation. 3) Anti-inflammatory benefits associated with bDMARDs treatments can differ despite similar drug efficacy against RA, indicating that drug-specific mechanisms are involved in regulating these processes. Acknowledgement Funded by PI-0285-2017, ISCIII, PI15/00837 and RIER RD16/0012/0015, co-funded with FEDER Disclosure of Interests Chary Lopez-Pedrera: None declared, Nuria Barbarroja Puerto: None declared, Carlos Perez-Sanchez: None declared, Alejandro Ibanez-Costa: None declared, Maria Luque-Tevar: None declared, Alejandra Patino-Trives: None declared, Ivan Arias de la Rosa: None declared, Maria del Carmen Abalos-Aguilera: None declared, Rafaela Ortega Castro: None declared, Alejandro Escudero Contreras: None declared, Perez Sanchez Laura: None declared, Carlos Rodriguez-Escalera: None declared, Dolores Ruiz-Montesinos: None declared, Carmen Maria Romero-Barco: None declared, Natalia Mena-Vazquez: None declared, Julia Uceda Speakers bureau: abbie, pfizer, novartis, janmsen, Ma Dolores Toledo-Coello: None declared, M angeles Aguirre-Zamorano: None declared, Eduardo Collantes Estevez: None declared