Abstract
Background: Adalimumab, golimumab, infliximab, certolizumab, and etanercept are five anti-tumor necrosis factor (anti-TNF) medicines that have been approved for use in rheumatology. Apart from their well-established therapeutic usefulness, -it is unclear to what extent -they are linked to an increased risk of various side effects. The present meta-analysis was carried out to assess the risk of infection and other side effects after anti-TNF- α for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Methods: We searched PubMed, Cinahl (via Ebsco), Scopus, and Web of Sciences databases for trials comparing anti-TNF medications to placebo or no therapy in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis from August 2006 to August 2020. A total of 23 articles were used for meta-analysis. The Cochrane Collaboration’s risk of bias tool was used to assess the methodological quality of the included studies. In addition, a random-effects model was used to calculate the pooled odds ratio, and Forest plots were constructed to determine the risk of infections and cancer following the use of anti-TNF treatment. Results: Treatment with anti-TNFα agents resulted in an increase in the risk of serious infections (OR: 1.72, 95% CI: 1.56–1.90, p < 0.00001) and an increase in cancer risk (OR: 1.36, 95% CI: 1.20–1.53, p < 0.00001) whereas the risk of developing tuberculosis was not significantly different with anti-TNFα agents versus those without treatment with anti-TNFα agents (OR: 2.55, 95% CI: 0.40–16.23, p = 0.32) although the number of studies is limited to make a definitive conclusion. The risk of bias of the included studies was unclear to high across most domains, and there was evidence of publication bias for most outcomes. Conclusion: The present meta-analysis suggests an increased risk of infectious adverse events, including overall adverse events and cancer following anti-TNFα treatment, whereas the risk of tuberculosis was not significantly different. Although anti-TNF agents have shown promise to treat inflammatory conditions, their use should be balanced by the risk-benefit ratio as suggested by the meta-analysis.
Highlights
Tumor necrosis factor (TNF) and interleukin-1 (IL-1) have been shown to play an essential role in the pathogenesis of inflammatory conditions such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) (Listing et al, 2005)
These biologic agents differ in structure, they all act by neutralizing TNFα, which is implicated in early inflammatory events associated with several conditions
TNFα inhibitors have been used in rheumatological conditions that are unresponsive to treatment with disease-modifying anti-rheumatic drugs (DMARDs) such as sulfasalazine, chloroquine, hydroxychloroquine, D penicillamine, and azathioprine, among others
Summary
Tumor necrosis factor (TNF) and interleukin-1 (IL-1) have been shown to play an essential role in the pathogenesis of inflammatory conditions such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) (Listing et al, 2005). Adalimumab and golimumab are fully human monoclonal antibodies; infliximab is a chimeric monoclonal antibody with a murine variable region; certolizumab is a humanized Fab fragment conjugated with polyethylene glycol, while etanercept is a fusion protein of two TNF2 receptor extracellular domains and the Fc fragment of human immunoglobulin 1 (Curtis et al, 2007; Minozzi et al, 2016). These biologic agents differ in structure, they all act by neutralizing TNFα, which is implicated in early inflammatory events associated with several conditions. The present metaanalysis was carried out to assess the risk of infection and other side effects after anti-TNFα for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis
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