Safety of biological therapy in patients with rheumatoid arthritis in administrative health databases: A systematic review and meta-analysis

Abstract

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].

Reducing cardiovascular risk in immune‐mediated inflammatory diseases: Tumour necrosis factor inhibitors compared to conventional therapies—A systematic review and meta‐analysis

“…Findings of two further meta‐analyses also supported the beneficial role of TNFis in CV risk in the RA population 18,99 . Although a recent meta‐analysis found no difference between TNFis and conventional DMARDs in terms of CV risk, 100 the review of the literature together with our results indicate the benefit of TNFis in patients with RA.…”

Drug retention of biologics and Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study

“… 33 Furthermore, a meta-analysis demonstrated that ABT was associated with a significantly lower risk of cardiovascular events than TNFi (risk ratio, RR=0.37; 95% CI: 0.24 to 0.55). 34 Conversely, the results from a large international registry revealed that JAKi were associated with a higher incidence of adverse event-related discontinuation than TNFi (adjusted HR=1.16, 95% CI: 1.03 to 1.33). 5 However, a recent systematic review and meta-analysis indicated only tendencies with relatively large variances and no significant differences in the safety profile between TNFi and JAKi (RR=3.54, 95% CI: 0.30 to 42.09).…”

“… 5 However, a recent systematic review and meta-analysis indicated only tendencies with relatively large variances and no significant differences in the safety profile between TNFi and JAKi (RR=3.54, 95% CI: 0.30 to 42.09). 34 Another meta-analysis showed that while ABT exhibited a slightly increased risk of malignancy, no such increased risk was observed with TOF and TCZ compared with TNFi. 35 Altogether, this study suggests that the higher retention rate of CTLA4-Ig was a result of its comparatively superior safety profile compared with TNFi and aIL-6R.…”