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Immunosafety of Recombinant Human C1-Inhibitor in Hereditary Angioedema: Evaluation of IgE Antibodies

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Abstract

Background

Recombinant human C1-inhibitor (rhC1INH) purified from milk of transgenic rabbits is used for the treatment of acute attacks in patients with hereditary angioedema (HAE) due to C1-inhibitor (C1INH) deficiency.

Objective

The objective was to investigate the risk of rhC1INH inducing IgE antibodies or eliciting anaphylactic reactions.

Methods

In subjects treated with rhC1INH, we retrospectively analysed the frequency and clinical relevance of pre-exposure and potentially newly induced IgE antibodies against rabbit and other animal allergens including cow’s milk by the ImmunoCAP® Specific IgE blood test system.

Results

130 HAE patients and 14 healthy subjects received 300 administrations of rhC1INH, 65 subjects (47.4 %) on one occasion; 72 (52.6 %) on at least two occasions (range 2–12; median 2). Five subjects had pre-existing anti-rabbit epithelium IgE; the subject with the highest levels and a previously undisclosed rabbit allergy developed an anaphylactic reaction upon first exposure to rhC1INH, whereas the other four subjects with lower pre-existing IgE levels (Class 1–3), did not. No other anaphylactic reactions were identified in any of the subjects exposed to rhC1INH. Analysis of post-exposure samples revealed that the risk of inducing new or boosting existing IgE responses to rabbit or cow’s milk allergens was negligible.

Conclusion

The propensity of rhC1INH to induce IgE antibodies following repeated administration of rhC1INH is low. Subjects with substantially elevated anti-rabbit epithelium IgE antibodies and/or clinical allergy to rabbits may have an increased risk for an allergic reaction. No other risk factors for allergic reactions to rhC1INH have been identified.

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Acknowledgements

All studies were funded by Pharming Technologies BV, Leiden, The Netherlands. Medical writing support was provided by Rick Flemming PhD, CMPP at The Word Bureau and was funded by Pharming Technologies BV. CEH has been a consultant to Pharming Technologies; AR, AB, BO and RP are (former) employees of Pharming Technologies.

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Authors and Affiliations

  1. Departments of Immunology, Dermatology and Rheumatology, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands

    C. Erik Hack

  2. Pharming Technologies BV, Leiden, The Netherlands

    Anurag Relan, Aartie Baboeram, Beatrijs Oortwijn & Rienk Pijpstra

  3. Department of Experimental Immunology and Department of Otorhinolaryngology, Amsterdam Medical Centre, Amsterdam, The Netherlands

    Serge Versteeg & Ronald van Ree

Authors
  1. C. Erik Hack
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  2. Anurag Relan
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  3. Aartie Baboeram
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  4. Beatrijs Oortwijn
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  5. Serge Versteeg
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  6. Ronald van Ree
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  7. Rienk Pijpstra
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Correspondence to C. Erik Hack.

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Hack, C.E., Relan, A., Baboeram, A. et al. Immunosafety of Recombinant Human C1-Inhibitor in Hereditary Angioedema: Evaluation of IgE Antibodies. Clin Drug Investig 33, 275–281 (2013). https://doi.org/10.1007/s40261-013-0064-2

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  • DOI: https://doi.org/10.1007/s40261-013-0064-2

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