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A Systematic Review and Meta-regression Analysis on the Impact of Increasing IgG Trough Level on Infection Rates in Primary Immunodeficiency Patients on Intravenous IgG Therapy

Abstract

Purpose

We conducted a systematic review and meta-regression analysis to evaluate the impact of increasing immunoglobulin G (IgG) trough levels on the clinical outcomes in patients with PID receiving intravenous immunoglobulin G (IVIG) treatment.

Methods

Systematic search was conducted in PubMed and Cochrane. Other relevant articles were searched by reviewing the references of the reviewed article. All clinical trials with documented IgG trough levels and clinical outcome of interest in patients receiving IVIG treatment were eligible to be included in this review. Meta-regression analysis was conducted using Comprehensive Meta-analysis Software. Additional sensitivity analyses were undertaken to evaluate the robustness of the overall results.

Results

Twenty-eight clinical studies with 1218 patients reported from year 2001 to 2018 were included. The mean IVIG dose used ranges from 387 to 560 mg/kg every 3 to 4 weekly, and mean IgG trough obtained ranges from 660 to 1280 mg/dL. Random-effects meta-regression slope shows that IgG trough level increases significantly by 73 mg/dL with every increase of 100 mg/kg dose of IVIG (p < 0.05). Overall infection rates reduced significantly by 13% with every increment of 100 mg/dL of IgG trough up to 960 mg/dL (p < 0.05).

Conclusion

This meta-analysis concludes that titrating the IgG trough levels up to 960 mg/dL progressively reduces the rate of infections, and there is less additional benefit beyond that. Further studies to validate this result are required before it can be used in clinical practice.

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Funding

The study received financial support from the Fundamental Research Grants Scheme by the Ministry of Higher Education of Malaysia (FRGS/1/2017/SKK09/UKM/02/5).

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LJL, NMS, and SMS contributed to the conception and design and conducted the systematic search of the study. All authors contributed to data analysis, drafting, and revising the article. All authors gave final approval of the version to be published and agreed to be accountable for all aspects of the work.

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Correspondence to Shamin Mohd Saffian.

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Lee, J.L., Mohamed Shah, N., Makmor-Bakry, M. et al. A Systematic Review and Meta-regression Analysis on the Impact of Increasing IgG Trough Level on Infection Rates in Primary Immunodeficiency Patients on Intravenous IgG Therapy. J Clin Immunol 40, 682–698 (2020). https://doi.org/10.1007/s10875-020-00788-5

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Keywords

  • Primary immunodeficiency
  • IVIG
  • IgG trough
  • infection rates
  • clinical outcomes