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

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 ant...

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Bibliographic Details
Published in:Clinical drug investigation 2013-04, Vol.33 (4), p.275-281
Main Authors: Hack, C. Erik, Relan, Anurag, Baboeram, Aartie, Oortwijn, Beatrijs, Versteeg, Serge, van Ree, Ronald, Pijpstra, Rienk
Format: Article
Language:English
Subjects:
Anaphylaxis - chemically induced
Angioedema
Angioedemas, Hereditary - drug therapy
Case-Control Studies
Complement C1 Inhibitor Protein - adverse effects
Complement C1 Inhibitor Protein - therapeutic use
Humans
Immunoglobulin E - biosynthesis
Internal Medicine
Medicine
Medicine & Public Health
Original Research Article
Pharmacology/Toxicology
Pharmacotherapy
Recombinant Proteins - adverse effects
Recombinant Proteins - therapeutic use
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Summary: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.
ISSN:1173-2563
1179-1918
DOI:10.1007/s40261-013-0064-2