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Development of interferon beta-neutralising antibodies in multiple sclerosis—a systematic review and meta-analysis

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Abstract

Purpose

Interferon beta (IFN-β) is the drug of choice for treatment of relapsing forms of multiple sclerosis and is known to reduce the frequency and severity of relapses. This systematic review determines the occurrence of neutralising antibodies (NAbs) against different formulations of IFN-β: IFN-β-1a Avonex™, IFN-β-1a Rebif™ and IFN-β-1b Betaferon/Betaseron™.

Methods

The databases used in the review included MEDLINE Ovid (from 1950 to March 2015), Embase Ovid (from 1980 to March 2015), CENTRAL on The Cochrane Library (2011, Issue 4) and ClinicalTrials.gov (from 1997 to March 2015). All studies that compared the efficacy of the different formulations of IFN-β in patients with relapsing forms of multiple sclerosis including IFN-β-1a Avonex™, IFN-β-1a Rebif™, IFN-β-1b Betaferon/Betaseron™ and IFN-β-1b Extavia™ were included.

Results

Assessment of randomised controlled trials demonstrated that Avonex™ was 76 % less likely than Rebif™ to lead to the formation of NAbs. Avonex™ was 88 % less likely than Betaferon/Betaseron™ to lead to the formation of NAbs. Similar findings were also observed in the non-randomised controlled studies, with Avonex™ having the lowest risk. The formation of NAbs was dose dependent: Avonex™ at 30 μg was 64 % less risky than Avonex™ at 60 μg.

Conclusions

Our data show that 2.0–18.9 % of patients developed NAbs to Avonex™, 16.5–35.4 % of patients developed NAbs to Rebif™ and 27.3–53.3 % of patients developed NAbs to Betaferon/Betaseron™.

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Acknowledgments

This work was supported by the MRC Centre for Drug Safety Science. Professor Sir Munir Pirmohamed is a NIHR Senior Investigator. Andrea Fittipaldo, Trials Search Co-ordinator, Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Review Group, Milan, Italy, assisted in the development of search strategies.

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Authors and Affiliations

  1. Clinical Research and Healthcare Innovations, Mazumdar Shaw Medical Centre, Narayana Health, 258/A Bommasandra Industrial Area Hosur Road, Bangalore, Karnataka, 560099, India

    Karthik Govindappa

  2. MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, England, UK

    Karthik Govindappa, Jean Sathish, Kevin Park & Munir Pirmohamed

  3. Department of Biostatistics, University of Liverpool, Liverpool, England, UK

    Jamie Kirkham

  4. The Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool, England, UK

    Munir Pirmohamed

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  1. Karthik Govindappa
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  2. Jean Sathish
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  4. Jamie Kirkham
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  5. Munir Pirmohamed
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Correspondence to Karthik Govindappa.

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Jamie Kirkham and Munir Pirmohamed are joint senior authors.

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Govindappa, K., Sathish, J., Park, K. et al. Development of interferon beta-neutralising antibodies in multiple sclerosis—a systematic review and meta-analysis. Eur J Clin Pharmacol 71, 1287–1298 (2015). https://doi.org/10.1007/s00228-015-1921-0

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