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Efficacy and Safety of Mipomersen: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

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Abstract

Aim

Our aim was to assess the efficacy and safety of mipomersen through a systematic review of the literature and a meta-analysis of the available clinical studies.

Methods

A systematic literature search in SCOPUS, PubMed Medline, ISI Web of Science and Google Scholar databases was conducted up to January 20, 2019, in order to identify clinical trials assessing the effect of mipomersen on lipoproteins, and the safety profile of mipomersen. Effect sizes for lipid changes were expressed as weighted mean differences (WMD) and 95% confidence intervals (CI). For safety analysis, odd ratios (OR) and 95% CI were calculated using the Mantel–Haenszel method. Data were pooled from 13 clinical studies comprising 49 arms, which included 1053 subjects overall, with 729 in the active-treated arm and 324 in the control arm.

Results

Meta-analysis of data suggested that mipomersen significantly reduced low-density lipoprotein cholesterol (WMD − 1.52, 95% CI − 1.85 to − 1.19; p < 0.001), total cholesterol (WMD − 1.55, 95% CI − 1.97 to − 1.13; p < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C) (WMD − 1.66, 95% CI − 2.06 to − 1.27; p < 0.001), lipoprotein(a) (WMD − 0.99, 95% CI − 1.37 to − 0.62; p < 0.001), apolipoprotein B (WMD − 1.66, 95% CI − 2.04 to − 1.27; p < 0.001), triglycerides (WMD –0.61, 95% CI − 0.76 to − 0.46, p < 0.001), very-low-density lipoprotein cholesterol (WMD − 0.58, 95% CI − 0.73 to − 0.43; p < 0.001) and apolipoprotein A-I (WMD − 0.25, 95% CI − 0.51 to − 0.001; p = 0.049) without affecting HDL-C levels (WMD 0.11, 95% CI − 0.03 to 0.26; p = 0.124). However, treatment with mipomersen was positively associated with an increased risk of discontinuation of treatment (OR 3.02, 95% CI 1.96–4.65; p < 0.001), injection-site reaction (OR 11.41, 95% CI 7.88–16.52; p < 0.001), hepatic steatosis (OR 4.96, 95% CI 1.99–12.39; p = 0.001), hepatic enzymes elevation (OR 3.61, 95% CI 2.09–6.24; p < 0.001) and flu-like symptoms (OR 2.02, 95% CI 1.45–2.81; p < 0.001).

Conclusion

Despite favourable effects on the lipid profile, some concerns are reinforced from the safety profile. As a matter of fact, mipomersen therapy is more likely discontinued and associated with increased risk of injection-site reactions, hepatic steatosis, hepatic enzyme elevation, and flu-like symptoms.

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Acknowledgements

Funding

This paper was written independently; no company or institution supported it financially. No professional writer was involved in the preparation of this meta-analysis.

Declaration of interest

Arrigo F.G. Cicero provided scientific consultancies for Mylan and Menarini; Alberto Corsini has received honoraria from AstraZeneca, AMGEN, Sanofi, Recordati, Novartis, MSD, Mediolanum, DOC, Mylan and Pfizer; Nicola Ferri has received honoraria from Daichii-Sankyo, DOC, Mylan and Pfizer; Federica Fogacci has served as a consultant to Mylan; Peter P. Toth has served on the speakers bureau of Amarin, Amgen, Kowa, Merck, Novo-Nordisk, Regeneron, Sanofi, and has served as a consultant to Amarin, Amgen, AstraZeneca, Kowa, Merck, Nov-Nordisk, and Theravance; Massimiliano Ruscica has no conflict of interest to declare.

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Author notes

  1. Federica Fogacci and Nicola Ferri contributed equally to the paper.

Authors and Affiliations

  1. Medical and Surgical Sciences Department, University of Bologna, Via Albertoni, 15, 40138, Bologna, Italy

    Federica Fogacci & Arrigo F. G. Cicero

  2. Drug Sciences Department, University of Padua, Padua, Italy

    Nicola Ferri

  3. CGH Medical Center, Sterling, IL, USA

    Peter P. Toth

  4. Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Peter P. Toth

  5. Pharmacological and Biomolecular Sciences Department, University of Milan, Milan, Italy

    Massimiliano Ruscica & Alberto Corsini

  6. IRCCS Multimedica, Milan, Italy

    Alberto Corsini

Authors
  1. Federica Fogacci
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  2. Nicola Ferri
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  3. Peter P. Toth
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  4. Massimiliano Ruscica
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  5. Alberto Corsini
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  6. Arrigo F. G. Cicero
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Corresponding author

Correspondence to Arrigo F. G. Cicero.

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Fogacci, F., Ferri, N., Toth, P.P. et al. Efficacy and Safety of Mipomersen: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Drugs 79, 751–766 (2019). https://doi.org/10.1007/s40265-019-01114-z

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