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.

Rheumatoid arthritis;Biological therapy;Tuberculosis;Systematic review;Meta-analysis;Network meta-analysis

Ji Xiaojian;Hu Lidong;Wang Yiwen;Man Siliang;Liu Xingkang;Song Chuan;Zhang Jiaxin;Zhu Jian;Zhang Jianglin;Huang Feng

Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China;Xiamen Key Laboratory of Translational Medicine for Nucleic Acid Metabolism and Regulation, Xiang’an Hospital of Xiamen University, Xiamen, Fujian 361102, China

中华医学杂志（英文版）

[1]Ji Xiaojian;Hu Lidong;Wang Yiwen;Man Siliang;Liu Xingkang;Song Chuan;Zhang Jiaxin;Zhu Jian;Zhang Jianglin;Huang Feng-.Risk of tuberculosis in patients with rheumatoid arthritis treated with biological and targeted drugs: meta-analysis of randomized clinical trials)[J].中华医学杂志（英文版）,2022(04):409-415

Peto

Risk,tuberculosis,patients,rheumatoid,arthritis,treated,biological,targeted,drugs,meta,analysis,randomized,clinical,trials,Background,Concerns,exist,regarding,potential,development,RA,We,assessed,systematically,whether,therapy,increased,risk,by,controlled,RCTs,Methods,literature,search,was,conducted,Embase,Cochrane,Library,China,Biology,Medicine,disc,evaluating,from,inception,through,August,Traditional,network,were,performed,each,biologics,class,odds,ratio,its,confidence,interval,calculated,primary,effect,measure,Results,In,total,studies,included,this,developed,compared,Also,tumor,necrosis,inhibitors,had,higher,probability,developing,than,placebo,However,demonstrated,that,there,difference,Noticeably,significantly,more,common,dose,receiving,low,tofacitinib,Conclusion,This,demonstrates,evidence,elevated,dependent,Rheumatoid,Biological,Tuberculosis,Systematic,review,Network

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