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Adverse symptoms with anti-TNF-alpha therapy in inflammatory bowel disease: systematic review and duration-response meta-analysis

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Abstract

Background

Anti-tumor necrosis factor-alpha (TNF-α) agents have considerable advances in treating inflammatory bowel disease (IBD). These drugs carry possible risk of adverse symptoms, and no meta-analysis has examined this issue and the potential duration-response relationship.

Purpose

The purpose of this study was to assess duration-response relationship between anti-TNF-α agents and risk of adverse symptoms from all available randomized control trials (RCTs) with placebo arms in IBD.

Methods

PubMed, OVID, and Cochrane Library were searched to January 2015. The RCTs comparing anti-TNF-α therapy with placebo in adults with IBD were eligible. We estimated pooled relative risks (RRs) of adverse symptoms for anti-TNF-α therapy and examined both non-linear and linear duration-response relations between therapy duration and significant related adverse symptoms.

Results

Twenty-three RCTs with 7325 patients were included. Adverse symptoms of headache, nausea/vomit, abdominal pain, fever, and arthralgia showed no significant relationship with anti-TNF-α therapy, respectively. Fatigue was significantly associated with anti-TNF-α therapy (RR 1.35, 95 % confidence interval (CI) 1.01–1.81), and subgroup analysis indicated that long therapy duration (>30 weeks) and combination without azathioprine (AZA) were two risk factors for the occurrence of fatigue (RR 1.74, 95 % CI 1.03–2.93; RR 1.65, 95 % CI 1.13–2.40). In the trials without AZA combination, there was a linear duration-response relationship between therapy duration and risk of fatigue (P = 0.0217), and duration of 35 weeks increased the risk of fatigue by 50 %.

Conclusion

This meta-analysis suggested a promotive effect of anti-TNF-α therapy to the occurrence of fatigue, and for the anti-TNF-α therapy without AZA combination, a linear duration-response relationship existed between therapy duration and risk of fatigue.

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Acknowledgments

This study is supported by grants from Chinese Ministry of Public Health, No. 201002020

Conflicts of interest

The authors declare that they have nothing to disclose

Authorship

Guarantor of the article: Jin Li

Author contributions

All the authors contributed to the design of the study. Fan Wang, Xue Lin and Jin Li conceived and drafted the study. Fan Wang and Xue Lin collected all data. Fan Wang analyzed and interpreted the data. Jin Li provided statistical advice and support. Fan Wang and Jin Li drafted the manuscript. All authors commented on drafts of the paper. All authors approved the final version of the manuscript.

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    Authors and Affiliations

    1. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China

      Fan Wang, Xue Lin, Qiu Zhao & Jin Li

    2. Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan, 430071, China

      Fan Wang, Xue Lin, Qiu Zhao & Jin Li

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    1. Fan Wang
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    Correspondence to Jin Li.

    Additional information

    Fan Wang and Xue Lin contributed equally to this work.

    Electronic supplementary material

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    Supplementary Figure 1

    Risk of bias graph (DOC 30 kb)

    Supplementary Figure 2

    Risk of bias summary (DOC 29 kb)

    Supplementary Figure 3

    Funnel plots of meta-analysis between anti-TNF-α therapy and adverse symptoms: headache (A), nausea/vomit (B), abdominal pain (C), fever (D), fatigue (E) and arthralgia (F). (DOC 42 kb)

    PRISMA Checklist (DOC 151 kb)

    PRISMA Flow Diagram (DOC 32 kb)

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    Wang, F., Lin, X., Zhao, Q. et al. Adverse symptoms with anti-TNF-alpha therapy in inflammatory bowel disease: systematic review and duration-response meta-analysis. Eur J Clin Pharmacol 71, 911–919 (2015). https://doi.org/10.1007/s00228-015-1877-0

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    • DOI: https://doi.org/10.1007/s00228-015-1877-0

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