ABS1061 COMPARING THE SAFETY OF ADALIMUMAB AND ETANERCEPT AS THE FIRST BIOLOGIC IN RHEUMATOID ARTHRITIS: A SIMULATED RANDOMIZED CONTROLLED TRIAL USING DATA FROM THE BIOBADABRASIL COHORT

Le résumé fourni par la source

Background: Among anti-TNF agents, etanercept has been associated with a lower risk of infections (including tuberculosis) compared to adalimumab in rheumatoid arthritis [1–3]. On the other hand, a recent network meta-analysis of randomized controlled trials did not observe a higher risk of overall serious adverse events (SAEs) with adalimumab, suggesting that it might even be the safest anti-TNF agent for RA in this regard [3]. These latter results were based mainly on indirect comparisons, as there is only one small open-label randomized controlled trial directly comparing adalimumab and etanercept in RA, which showed a similar risk of SAEs. However, the conclusions of this trial were limited by the low number (only 13) of such events [4]. Objectives: To compare the incidence of serious adverse events between adalimumab and etanercept used as first biologic agents in rheumatoid arthritis (RA), simulating the conditions of a randomized controlled trial (RCT). Methods: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first biologic disease modifying anti-rheumatic drug (b-DMARD) or a Janus kinase inhibitor. The present analysis includes biologic-naïve RA patients (recruited from Jan 2009 to Oct 2019) on their first course of adalimumab or etanercept (latest date of follow-up, Nov 19, 2019). The primary outcome was the incidence of the first serious adverse event (SAE). A SAE was defined as a condition that causes death or is life threatening, leads to inpatient hospitalization or prolongation of an existing one, or causes important or persistent disability or a congenital abnormality/birth defect; pregnancy was included among SAEs. The secondary outcomes were the first adverse event (of any type), total and serious infections, mycobaterial infections, treatment interruption for any reason (except remission or pregnancy), interruption due to adverse events, and interruption of therapy due to inefficacy. Propensity scores were generated using logistic regression. We then used inverse probability of treatment weighting (IPTW), which simulates the conditions of a RCT, to calculate the weight of each case. After that, we used weighted Cox proportional hazards models to perform statistical analysis, employing robust standard errors and truncating extreme weight values (at the 1st and 99th percentiles) to account for the additional variance introduced by IPTW and to reduce the influence of outliers, respectively. A weighted Kaplan-Meier plot was used to visually compare the curves of SAE-free survival between the study groups. Analyses were performed using SPSS for Windows 20.0 and the survival package of R software. Results: In total, 687 RA patients (2184 patient-years [PY] of follow-up), 405 on treatment with adalimumab and 282 on etanercept, were enrolled after exclusion of five patients producing extreme imbalance between the groups (all in etanercept group, 4 with cancer and 1 receiving cyclosporine). IPTW produced pseudo samples with good comparability, with maximal standardized differences of 0.08 in covariates. The overall incidence of SAE was 5.8/100 PY. There was no significant difference in the risk of SAE between adalimumab and etanercept (reference group), with a hazard ratio of 0.87 (95% CI: 0.60 to 1.26, P=0.469; see the Figure 1). There was also no significant difference in the risk of the first adverse event (0.90, 0.72 to 1.12, P=0.346), total infections (0.88, 0.65 to 1.18, P=0.387), serious infections (0.81, 0.49 to 1.37, P=0.441), treatment interruption for any reason (1.00, 0.81 to 1.23, P=0.977), interruption of treatment due to adverse events (1.04, 0.70 to 1.54, P=0.866) and due to inefficacy (1.13, 0.84 to 1.51, P=0.420). The incidence of mycobacterial infections was numerically higher in adalimumab group (0.43/100 PY vs 0.29/100 PY in etanercept group; hazard ratio 1.63, 0.40 to 6.56, P=0.494). Conclusion: In the present study, adalimumab and etanercept did not differ significantly in the risk of SAEs, total infections, or serious infections, demonstrating an overall similar safety profile in Brazilian patients with RA. However, a numerical imbalance with regard to mycobacterial infections was observed, favoring etanercept. REFERENCES: [1] van Dartel SA et al. Ann Rheum Dis 2013;72:895-900. [2] Chiang YC et al. Comput Methods Programs Biomed 2014;116:319-27. [3] He B et al. Front Immunol 2022;13:814429. [4] Jobanputra P et al. BMJ Open 2012;2:e001395. Figure 1 Acknowledgements: Brazilian Society of Rheumatology and Patricia Cabral (monitor) Disclosure of Interests: Markus Bredemeier: None declared, Everson Reginatto: None declared, Marina Silvestri Pauwelz: None declared, Angela Duarte: None declared, Marcelo Pinheiro Abbvie, Janssen, UCB, Abbvie, Janssen, UCB, Barbara Stadler Kahlow: None declared, Monica Valeria Siqueira De Vechi: None declared, Roberto Ranza: None declared, Jose Roberto Miranda: None declared, Valéria Valim: None declared, Glaucio Castro Abbvie, Lilly, Janssen, UCB, Manoel Bertolo: None declared, Maria de Fátima Sauma: None declared, Vander Fernandes: None declared, Ana Cristina Medeiros-Ribeiro: None declared, Reginaldo Botelho: None declared, Claiton Brenol: None declared, Hellen Mary da Silveira de Carvalho: None declared, Samia Studart: None declared, Geraldo da Rocha Castelar Pinheiro: None declared, Laurindo Rocha Jr: None declared, Hugo de Leon de Lima: None declared, Ivanio Pereira: None declared, Morgana Ohira Gazzeta: None declared, Adriana Maria Kakehasi Abbvie, Lilly, Janssen, Organon, Pfizer, UCB, Abbvie, Janssen, Organon, Pfizer, Abbvie, Novartis, Pfizer, UCB, Paulo Louzada Jr: None declared, Andre Luiz Shinji Hayata: None declared, Cristiano Lupo: None declared, Ines Guimaraes Silveira: None declared, Sergio Kowalski: None declared, David Titton: None declared, Aline Ranzolin: None declared, Ricardo Machado Xavier Abbvie, UCB, Janssen, Organon, Abbvie, UCB, Ieda Maria Laurindo Abbvie, Janssen, Abbvie, Bristol, Janssen, Novartis, Pfizer, UCB, Abbvie, Boering, Bristol, Janssen, Lilly, Pfizer, UCB, Jose Eduardo Martinez: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.