The Risk of Tuberculosis in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor-α Antagonist: A Metaanalysis of Both Randomized Controlled Trials and Registry/Cohort Studies

Ai, Jingwen; Zhang, Shu; Ruan, Qingwei; Yu, Yiqi; Zhang, Bingyan; Liu, Qihui; Zhang, Wenhong

doi:10.3899/jrheum.150057

Cited by 86 publications

(64 citation statements)

References 28 publications

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“…This finding was comparable to the result of a meta-analysis of randomized controlled trials and registry/cohort studies [10]. The risk of TB infection in ETN users has been demonstrated to be lower than that in patients taking monoclonal antibodies to TNF [13, 23, 27].…”

Section: Discussionsupporting

confidence: 82%

“…Tumor necrosis factor (TNF) plays a key role in the immunity against TB [9]. In recent years, the use of a TNF inhibitor (TNFi) in RA patients further increased the TB risk [7, 10–12]. Furthermore, prior studies have shown that monoclonal antibodies to TNF, such as infliximab (IFX) and adalimumab (ADA), may drive higher TB risk than TNF receptor blockers such as etanercept (ETN) [10, 13].…”

Section: Introductionmentioning

confidence: 99%

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One-Year Tuberculosis Risk in Rheumatoid Arthritis Patients Starting Their First Tumor Necrosis Factor Inhibitor Therapy from 2008 to 2012 in Taiwan: A Nationwide Population-Based Cohort Study

et al. 2016

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ObjectiveTo investigate the risk of tuberculosis (TB) among rheumatoid arthritis (RA) patients within 1 year after initiation of tumor necrosis factor inhibitor (TNFi) therapy from 2008 to 2012.MethodsWe used the 2003–2013 Taiwanese National Health Insurance Research Database to identify RA patients who started any RA-related medical therapy from 2008 to 2012. Those who initiated etanercept or adalimumab therapy during 2008–2012 were selected as the TNFi group and those who never received biologic disease-modifying anti-rheumatic drug therapy were identified as the comparison group after excluding the patients who had a history of TB or human immunodeficiency virus infection/acquired immune deficiency syndrome. We used propensity score matching (1:6) for age, sex, and the year of the drug index date to re-select the TNFi group and the non-TNFi controls. After adjusting for potential confounders, hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to examine the 1-year TB risk in the TNFi group compared with the non-TNFi controls. Subgroup analyses according to the year of treatment initiation and specific TNFi therapy were conducted to assess the trend of 1-year TB risk in TNFi users from 2008 to 2012.ResultsThis study identified 5,349 TNFi-treated RA patients and 32,064 matched non-TNFi-treated controls. The 1-year incidence rates of TB were 1,513 per 105 years among the TNFi group and 235 per 105 years among the non-TNFi controls (incidence rate ratio, 6.44; 95% CI, 4.69–8.33). After adjusting for age, gender, disease duration, comoridities, history of TB, and concomitant medications, TNFi users had an increased 1-year TB risk (HR, 7.19; 95% CI, 4.18–12.34) compared with the non-TNFi-treated controls. The 1-year TB risk in TNFi users increased from 2008 to 2011 and deceased in 2012 when the Food and Drug Administration in Taiwan announced the Risk Management Plan for patients scheduled to receive TNFi therapy.ConclusionThis study showed that the 1-year TB risk in RA patients starting TNFi therapy was significantly higher than that in non-TNFi controls in Taiwan from 2008 to 2012.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

One-Year Tuberculosis Risk in Rheumatoid Arthritis Patients Starting Their First Tumor Necrosis Factor Inhibitor Therapy from 2008 to 2012 in Taiwan: A Nationwide Population-Based Cohort Study

et al. 2016

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“…53 One study estimated that preventive treatment in patients with LTBI can reduce the risk of reactivation by 65% 10. Some countries have formulated national guidelines to deal with LTBI before anti-TNF agents treatment 54.…”

Section: Discussionmentioning

confidence: 99%

“…Although their therapeutic efficacy has been confirmed, the side effects of these TNF-α antagonists need to be considered carefully in clinical practice 8. An increased risk of tuberculosis (TB) among patients receiving TNF-α antagonists has been observed,9 and several meta-analyses have evaluated the risk of TB in patients treated with TNF-α antagonists or with specific conditions 10–13. Nevertheless, the association between TNF-α antagonists and an increased risk of TB remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Risk of tuberculosis in patients treated with TNF-α antagonists: a systematic review and meta-analysis of randomised controlled trials

et al. 2017

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ObjectivesAn increased risk of tuberculosis (TB) has been reported in patients treated with TNF-α antagonists, an issue that has been highlighted in a WHO black box warning. This review aimed to assess the risk of TB in patients undergoing TNF-α antagonists treatment.MethodsA systematic literature search for randomised controlled trials (RCTs) was performed in MEDLINE, Embase and Cochrane library and studies selected for inclusion according to predefined criteria. ORs with 95% CIs were calculated using the random-effect model. Subgroup analyses considered the effects of drug type, disease and TB endemicity. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.Results29 RCTs involving 11 879 patients were included (14 for infliximab, 9 for adalimumab, 2 for golimumab, 1 for etanercept and 3 for certolizumab pegol). Of 7912 patients allocated to TNF-α antagonists, 45 (0.57%) developed TB, while only 3 cases occurred in 3967 patients allocated to control groups, resulting in an OR of 1.94 (95% CI 1.10 to 3.44, p=0.02). Subgroup analyses indicated that patients of rheumatoid arthritis (RA) had a higher increased risk of TB when treated with TNF-α antagonists (OR 2.29 (1.09 to 4.78), p=0.03). The level of the evidence was recommended as ‘low’ by the GRADE system.ConclusionsFindings from our meta-analysis indicate that the risk of TB may be significantly increased in patients treated with TNF-α antagonists. However, further studies are needed to reveal the biological mechanism of the increased TB risk caused by TNF-α antagonists treatment.

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“…Although the numbers were small for comparison, this study confirmed prior data showing the lowest risk occurred among those exposed to ETN versus ADA or IFX. A meta-analysis of randomized trials and registry/cohort studies essentially confirmed these findings [15].…”

Section: Introductionmentioning

confidence: 64%

Infection, malignancy, switching, biosimilars, antibody formation, drug survival and withdrawal, and dose reduction

Ianculescu

Weisman²

2016

Current Opinion in Rheumatology

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TNFi agents have made their powerful impact on management of patients with rheumatoid arthritis, but questions remain: what is their true infection and malignancy risk in the evolving populations using these drugs today; are we able to maintain their benefit with a reduced schedule (and presumed less cost) and yet recapture their benefit if we guess wrong; are biosimilars just as good, or even better with less cost; are there data to inform us about how to achieve successful switching among different mechanism of action TNFi agents? Finally, are we going to face the specter of cost containment causing change from innovator to biosimilars over which we have no control?

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The Risk of Tuberculosis in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor-α Antagonist: A Metaanalysis of Both Randomized Controlled Trials and Registry/Cohort Studies

Abstract: This study demonstrated a significant increase in TB risk in patients with RA treated with TNF-α antagonists; among them, ETN is least likely to cause active TB. The study also proposes the necessity of LTBI prophylaxis in patients with RA.

Cited by 86 publications

References 28 publications

One-Year Tuberculosis Risk in Rheumatoid Arthritis Patients Starting Their First Tumor Necrosis Factor Inhibitor Therapy from 2008 to 2012 in Taiwan: A Nationwide Population-Based Cohort Study

One-Year Tuberculosis Risk in Rheumatoid Arthritis Patients Starting Their First Tumor Necrosis Factor Inhibitor Therapy from 2008 to 2012 in Taiwan: A Nationwide Population-Based Cohort Study

Risk of tuberculosis in patients treated with TNF-α antagonists: a systematic review and meta-analysis of randomised controlled trials

Infection, malignancy, switching, biosimilars, antibody formation, drug survival and withdrawal, and dose reduction

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