Risk of Adverse Events After Anti-TNF Treatment for Inflammatory Rheumatological Disease. A Meta-Analysis

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.

Keywords: ankylosing spondylitis; anti TNF therapy; malignancy; psoriatic arthritis (artritis psoriatica); rheumatoid arthritis; risk of infections.

FIGURE 1

Flow chart for identification and inclusion of studies in the meta-analysis (PRISMA statement).

FIGURE 2

(A) Forest plot for overall adverse events after treatment with anti-TNFα agents versus control group (without anti-TNFα agents) using a random-effects model. Odds ratios and 95% confidence intervals are shown (B) Funnel plot for assessment of publication bias.

FIGURE 3

(A) Forest plot for serious infection after treatment with anti-TNFα agents versus control group (without anti-TNFα agents) using a random-effects model. Odds ratios and 95% confidence intervals are shown (B) Funnel plot for assessment of publication bias.

FIGURE 4

(A) Forest plot for tuberculosis infection after treatment with anti-TNFα agents versus control group (without anti-TNFα agents) using a random-effects model. Odds ratios and 95% confidence intervals are shown (B) Funnel plot for assessment of publication bias.

FIGURE 5

(A) Forest plot for cancer incidence after treatment with anti-TNFα agents versus control group (without anti-TNFα agents) using a random-effects model. Odds ratios and 95% confidence intervals are shown. (B) Funnel plot for assessment of publication bias.

FIGURE 6

Risk of bias summary for randomized controlled trials and prospective studies included in the meta-analysis (+): low risk of bias (+): high risk of bias (?): unclear risk of bias.