Background: The use of biological and targeted synthetic drugs has changed the outcomes of rheumatic diseases. The information on efficacy and safety provided by randomized controlled clinical trials does not always reflect the conditions of patients in real life. Data obtained from prospective registries, over extended periods and with real-world evidence, is a great contribution to the pharmacovigilance of these drugs.

Objectives: The aim of this study is to describe adverse events (AE) and survival of treatments of patients included in the Argentine Registry of Adverse Events of Biological Therapies and Target Synthetic Drugs (BIOBADASAR 3.0).

Methods: Observational, prospective and multicenter study of ten years of follow-up in patients with rheumatic diseases treated with original biological drugs, biosimilars or original and generic targeted synthetic therapies in Argentine. Those patients who received biological therapies were considered exposed while non-exposed patients represent the control group. All patients were evaluated at least once a year and whenever they experienced an AE or a change in treatment. Survival of treatments was evaluated by Kaplan Meier curves and the comparison between them was made by Log Rank Test analysis.

Results: A total of 6010 patients were included and 8810 treatment periods from 56 centers. 79.7% were female, mean age of 43.7 (SD 15.6) years. The most frequently reported rheumatological disease was rheumatoid arthritis (RA) (77.5%), followed by psoriatic arthritis (PsA) (8.2%), systemic lupus erythematosus (SLE) (3.1%), juvenile idiopathic arthritis (JIA) (2.6%) and ankylosing spondylitis (AS) (2.5%). The b-DMARD use frequencies were etanercept in 32.2%, followed by adalimumab in 18.7%, abatacept in 9.7%, certolizumab pegol in 8.7%, tofacitinib in 7.9%, rituximab in 7.3% and tocilizumab in 5.5%. The frequency of AE was 11.7% in the exposed group and 4.9% in controls (p=0.001). Infections were present in 41% in the exposed group vs 34% in controls (p<0.001). AE-free survival was 23 years [IQR: 18.2] in controls vs 10 years [IQR: 8.8]) in the exposed group p<0.0001). In the multivariate regression model, age (HR: 1.005, 95% CI 1.001-1.009) and corticosteroid treatment (HR: 1.18, 95% CI 1.05-1.34) were associated with a higher risk of AE in exposed patients. Treatment survival was 15 years [IQR: 28] in unexposed group vs 4.7 years [IQR: 10] in exposed patients (p<0.0001). In the multivariate analysis, female sex (HR 1.1, 95% CI 1.09-1.2), older age (HR 1.0, 95% CI: 1.010-1.014), corticosteroid treatment (HR 1.16, 95% CI 1.09-1.2), the diagnosis of systemic lupus erythematosus (HR1.547, CI95%1.3-1.8) and disease duration (HR1.01, CI95%1.008-1.015) were associated with a higher risk of treatment discontinuation while the diagnosis of rheumatoid arthritis (HR 0.83 CI95% 0.75-0.93) was associated with a lower risk of suspension.

Conclusion: We found that the use of steroids and elderly patients are still being associated with a higher risk of presenting an AE and treatment discontinuing. This could be related to the fact that the use of steroids is frequently associated with active disease or severe conditions. Exposed patients have a lower AE-free survival and a lower treatment survival. This could be since unexposed patients have a longer follow-up time and a longer duration of their disease. This data from real-world Latin American patients of ten years of follow-up are extremely useful for monitoring and pharmacovigilance of biological therapies in patients with rheumatic diseases.

REFERENCES:

[1]De la Vega M, et al. The importance of rheumatology biologic registries in Latin America. Rheumatol Int. 2013;33(4):827-35. Rocha FA. Latin-American challenges and opportunities in rheumatology. Arthritis Res Ther. 2017;19(1):29.

[2]Prior-Español A, et al. Clinical factors associated with discontinuation of ts/bDMARDs in rheumatic patients from the BIOBADASER III registry. Sci Rep. 2021 May 27;11(1):11091. doi: 10.1038/s41598-021-90442-w. PMID: 34045525; PMCID: PMC8159943.

Disclosure of Interests: None declared