This preprint is under consideration at Arthritis Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research article
Peng Wenxing
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7032-7293
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Background The risk of tumor necrosis factor-α(TNF-α) inhibitors (infliximab, etanercept, adalimumab) for the treatment of rheumatic diseases leading to infection events has not yet been established. This meta-analysis aims to assess the risk of developing serious infections of three TNF-α inhibitors for rheumatic diseases.
Methods A systematic literature search of Pubmed, Embase and Cochrane Library was conducted through December 2018. Selecting the RCTs which subjects were diagnosed as rheumatoid diseases according to ACR criteria or other authoritative diagnostic criteria and over 18-year-old. Finally, RCTs with Jadad score greater than or equal to 4 were included in this meta-analysis. The Odds Ratio (OR), Confidence Interval (CI) and p value were calculated to assess the risk of serious infections.
Results 34 RCTs involving 14166 subjects were included, including 11 RCTs for infliximab, 7 RCTs for etanercept, and 16 for adalimumab. Meta-analysis demonstrated that, with the pooled OR of 1.29 (95%CI 1.04 to 1.60), the TNF-α inhibitors group had a higher risk of serious infection than control group. In the subgroup analysis, infliximab and adalimumab had a higher risk of serious infection than control group, and the pooled ORs were 1.48 (p=0.03) and 1.47 (p=0.03), respectively. For other infections including pneumonia, upper respiratory infection, and nasopharyngitis, the risks of these adverse events were higher in experimental group than control group, while the risk of tuberculosis were not, with the pooled OR of 2.31 (p=0.08）.
Conclusions TNF-α inhibitors, especially infliximab and adalimumab, can increase the risk of infections. Among the infections, pneumonia, upper respiratory infection and nasopharyngitis have higher risks in TNF-α inhibitors group than control group. As a result, we summarized that TNF-α inhibitors can increase the risks of respiratory infection when used in rheumatic disease. It is suggested that clinicians should pay attention to the prevention of respiratory infections when using TNF-α inhibitors, so as to achieve a better prognosis for patients with rheumatism.
Keywords
TNF-α inhibitors; infliximab; etanercept; adalimumab; infections; meta-analysis
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This preprint is under consideration at Arthritis Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Peng Wenxing
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7032-7293
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 13 Mar, 2020
No community comments so far
Editor assigned
On 13 Mar, 2020
Editor invited
On 12 Mar, 2020
Submission checks complete
On 11 Mar, 2020
First submitted
On 10 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Rheumatology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background The risk of tumor necrosis factor-α(TNF-α) inhibitors (infliximab, etanercept, adalimumab) for the treatment of rheumatic diseases leading to infection events has not yet been established. This meta-analysis aims to assess the risk of developing serious infections of three TNF-α inhibitors for rheumatic diseases.
Methods A systematic literature search of Pubmed, Embase and Cochrane Library was conducted through December 2018. Selecting the RCTs which subjects were diagnosed as rheumatoid diseases according to ACR criteria or other authoritative diagnostic criteria and over 18-year-old. Finally, RCTs with Jadad score greater than or equal to 4 were included in this meta-analysis. The Odds Ratio (OR), Confidence Interval (CI) and p value were calculated to assess the risk of serious infections.
Results 34 RCTs involving 14166 subjects were included, including 11 RCTs for infliximab, 7 RCTs for etanercept, and 16 for adalimumab. Meta-analysis demonstrated that, with the pooled OR of 1.29 (95%CI 1.04 to 1.60), the TNF-α inhibitors group had a higher risk of serious infection than control group. In the subgroup analysis, infliximab and adalimumab had a higher risk of serious infection than control group, and the pooled ORs were 1.48 (p=0.03) and 1.47 (p=0.03), respectively. For other infections including pneumonia, upper respiratory infection, and nasopharyngitis, the risks of these adverse events were higher in experimental group than control group, while the risk of tuberculosis were not, with the pooled OR of 2.31 (p=0.08）.
Conclusions TNF-α inhibitors, especially infliximab and adalimumab, can increase the risk of infections. Among the infections, pneumonia, upper respiratory infection and nasopharyngitis have higher risks in TNF-α inhibitors group than control group. As a result, we summarized that TNF-α inhibitors can increase the risks of respiratory infection when used in rheumatic disease. It is suggested that clinicians should pay attention to the prevention of respiratory infections when using TNF-α inhibitors, so as to achieve a better prognosis for patients with rheumatism.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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