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Bayesian Network Meta-Analysis for Assessing Adverse Effects of Anti-hepatitis B Drugs

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Abstract

Background and Objective

Oral nucleoside/nucleotide analogues (NAs) have been advocated for chronic hepatitis B (CHB) treatment with good efficacy. However, less attention has been put on their adverse events. Therefore, a Bayesian network meta-analysis (NMA) was performed to evaluate the relative safety of five NAs (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate) in CHB treatment among adults.

Methods

Eligible randomized clinical trials (RCTs) and prospective cohort studies were systematically and thoroughly searched until May 1, 2019. Poisson-prior-based Bayesian NMA was performed to synthesize both direct and indirect evidence with reporting hazard ratios (HRs) and 95% credible intervals (CrIs) for serious adverse events (SAEs) and hepatic/renal impairments.

Results

Thirty-three RCTs and 11 prospective cohort studies were identified. As to SAEs, no statistically significant difference was found of any comparison among five NAs. In terms of hepatotoxicity, lamivudine was safer than telbivudine (HR 0.45; 95% CrI 0.21, 0.85), and entecavir increased the risk by 102% (entecavir vs lamivudine: HR 2.02; 95% CrI 1.19, 3.27).

Conclusions

The findings from this large NMA could influence clinical practice, and the methodological framework of this study could provide evidence-based support to analyze sparse safety data in the field.

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Author notes

  1. Yi Shen and Yulong Jia contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, China

    Yi Shen, Yulong Jia, Jie Zhou & Juling Ji

  2. Medical School of Nantong University, No. 19, Qixiu Rd, Nantong, Jiangsu, 226001, China

    Juling Ji

  3. Department of Epidemiology and Biostatistics, School of Public Health-Bloomington, Indiana University, 1025 E 7th Street C103, Bloomington, IN, 47405, USA

    Pengcheng Xun

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  1. Yi Shen
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  4. Juling Ji
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Contributions

Concept and design: YS, YLJ, JLJ, PCX. Statistical analysis: YLJ, JZ. Methodology: YLJ, JZ. Validation: YS, YLJ, JLJ, PCX. Writing—original draft: YS, YLJ, JZ. Writing—critical review and editing: YS, JLJ, PCX. All authors approved the final version of the manuscript.

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Correspondence to Juling Ji or Pengcheng Xun.

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Yi Shen, Yulong Jia, Jie Zhou, Juling Ji, Pengcheng Xun have no conflicts of interest that are directly relevant to the content of this article.

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Shen, Y., Jia, Y., Zhou, J. et al. Bayesian Network Meta-Analysis for Assessing Adverse Effects of Anti-hepatitis B Drugs. Clin Drug Investig 39, 835–846 (2019). https://doi.org/10.1007/s40261-019-00802-8

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