RESUMEN
Background: The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically, it starts with conventional synthetic DMARDs (csDMARDs), and depending on the patient's response to the treatment and the adverse events experienced, biological DMARDs (bDMARDs) are initiated. bDMARDs are more specific to inflammatory factors than csDMARDs and more efficient in inducing remission and low disease activity. Thus, this study aimed to assess the effectiveness of biological therapy in patients with rheumatoid arthritis in administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science databases were searched from inception to 21 October 2021, to identify observational studies that evaluated the effectiveness of biological therapy in patients with rheumatoid arthritis using administrative databases and real-world data. The methodological quality was assessed by the methodological index for non-randomized studies (MINORS). A fixed or random-effects model estimated risk ratios with 95% confidence intervals. The analysis was divided into four groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus TNFi (adalimumab, etanercept, and golimumab versus infliximab); bDMARDs versus Janus kinase inhibitors (JAKi); and bDMARDs monotherapy versus combination therapy (bDMARDs and MTX). Results: Twenty-one records were eligible for inclusion in this systematic review and meta-analysis; seven population-based cohorts, eight prospective, and six retrospective cohort studies. Overall, 182,098 rheumatoid arthritis patients were evaluated. In the meta-analysis, lower effectiveness was observed among TNFi users than in non-TNFi (RR: 0.88; 95% CI: 0.81-0.95; p < 0.01; I2 = 94.0%) and bDMARDs than in JAKi (RR: 0.86; 95% CI: 0.79-0.94; p < 0.01; I2 = 93.0%). Higher effectiveness among adalimumab, etanercept, and golimumab than in infliximab (RR: 1.19; 95% CI: 1.05-1.36; p < 0.01; I2 = 96.0%) was found. No significant differences in the effectiveness of bDMARD monotherapy compared to combination therapy (RR: 0.83; 95% CI: 0.68-1.00; p < 0.01; I2 = 81.0%) was observed. E-value analysis indicated that the estimates were not robust against unmeasured confounding. Conclusion: According to the available real-world data, our results suggest that biological therapy effectively treats patients with rheumatoid arthritis, indicating higher effectiveness with non-TNFi and JAKi than with TNFi. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID#CRD42020190838, identifier CRD42020190838.
RESUMEN
Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects the synovial fluid of joints, tendons, and some extra-articular sites. Biologic agents have been highly effective and are comparable in reducing RA symptoms, slowing disease progression, and improving physical function; however, concerns have been raised about the risks of several potential adverse effects. Thus, this study aimed to assess the safety of biological therapy in patients with rheumatoid arthritis in observational studies using administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science were searched from inception to 21 October 2021. The analysis was divided into five groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus csDMARDs; bDMARDs versus csDMARDs; abatacept versus bDMARDs; and TNFi versus Janus kinase inhibitors (JAKi). The adverse events were cancer, cardiovascular events, infection, herpes zoster, tuberculosis, and death. The methodological quality of the studies was assessed by the Newcastle-Ottawa Scale. A random-effects model estimated risk ratios with 95% confidence intervals. Results: Thirty-one studies were eligible for inclusion in the present systematic review, published from 2014 to 2021. A total of 1,039,398 RA patients were assessed. The 31 studies evaluated eleven different biological drugs. No significant differences were found regarding safety between TNFi versus non-TNFi (RR 1.08; 95% CI 0.92-1.28; p < 0.01; I2 = 93.0%), TNFi versus csDMARDs (RR 0.91; 95% CI 0.75-1.10; p < 0.01; I2 = 87.0%), bDMARDs versus csDMARDs (RR 0.99; 95% CI 0.82-1.20; p < 0.01; I2 = 93.0%), abatacept versus bDMARDs (RR 0.80; 95% CI 0.54-1.18; p < 0.01; I2 = 90.0%), and TNFi versus JAKi (RR 3.54; 95% CI 0.30-42.09; p = 0.01; I2 = 81.0%). In the subgroup analysis, among studies comparing abatacept to TNFi, a lower risk of cardiovascular events was associated with abatacept (RR 0.37; 95% CI 0.24-0.55). Conclusion: Our results do not suggest an increased risk of adverse events associated with biological therapy in treating RA patients, indicating a lower risk of cardiovascular events with abatacept than TNFi. However, these findings must be interpreted with caution given the limitations of this study and the low/very low certainty of the evidence. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier [CRD42020190838].
