Risk of tuberculosis in patients with rheumatoid arthritis treated with biological and targeted drugs: meta-analysis of randomized clinical trials

Abstract

Background:Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs).Methods:A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure.Results:In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36–6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30–6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00–27.31, P = 0.003).Conclusion:This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

“…Screening for latent TB before starting bDMARDs is included in screening programmes of most national and international rheumatology associations, while the same applies for tsDMARDs, although there is less evidence 27–32. On the other hand, there is some evidence that patients with AIIRD under treatment with csDMARDs and/or glucocorticoids have also increased risk for latent TB reactivation 29 33–37.…”

Screening for latent infectious disease in patients with alopecia areata before initiating JAK inhibitors therapy: a single-center real-world retrospective study

“…Amony the 30 patients of LTBI, only 1 patient who refused LTBI prophylaxis treatment received tofacitinib treatment and reexamination of chest CT showed no obvious changes after 6 months. Despite the disease tends for AA to be prevalent in younger patients, the data that observed in larger, long-term studies of patients with rheumatoid arthritis strongly suggest a link between activation of tuberculosis and JAKi ( 18 , 19 ). In additional, our data showed that the proportion of tuberculosis infections detected among patients over 40 years is 43%, which decreased to 11% in the 18–40 age group.…”

Epidemiology: the current burden of tuberculosis and its determinants

“…Other conditions increase the risk of progression from infection to disease. These include silicosis (RR 4-30) [115,116], kidney failure (RR 10-25) [117,118], rheumatoid arthritis (RR 2-16) [111] and cancer (RR 2-40) [119][120][121]. In each of the conditions, the immune system is affected by the required treatment, making the patient less capable of self containing M. tuberculosis infection.…”