Allergenicity and safety of recombinant human C1 esterase inhibitor in patients with allergy to rabbit or cow's milk

• Published in: Journal of allergy and clinical immunology Vol. 138; no. 2; pp. 476 - 481.e1
• Main Authors: van den Elzen, Mignon T., MD, van Os-Medendorp, Harmieke, PhD, Röckmann-Helmbach, Heike, MD, PhD, van Hoffen, Els, PhD, Lebens, Ans F.M., BSc, van Doorn, Helma, BAS, Klemans, Rob J.B., MD, PhD, Bruijnzeel-Koomen, Carla A.F.M., MD, PhD, Hack, C. Erik, PhD, Kaufman, Leonard, PhD, Relan, Anurag, MD, Knulst, André C., MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01.08.2016
• Subjects: Adult; Allergy and Immunology; Angioedemas, Hereditary - complications; Angioedemas, Hereditary - drug therapy; Animals; Cattle; Complement C1 Inhibitor Protein - adverse effects; Complement C1 Inhibitor Protein - therapeutic use; Drug dosages; Female; Food allergies; Humans; Immunoglobulin E - immunology; Male; Middle Aged; Milk; Milk - adverse effects; Milk Hypersensitivity - complications; Milk Hypersensitivity - diagnosis; Milk Hypersensitivity - immunology; Patients; Phenotype; Proteins; Rabbits; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Severity of Illness Index; Skin; Skin Tests; Young Adult; sIgE; recombinant human C1 esterase inhibitor; Basophil activation test; allergenicity; C1 esterase inhibitor; SC; NPV; CMA; SPT; rabbit allergy; cow's milk allergy; AE; Specific IgE; Subcutaneous; subcutaneous administration; Negative predictive value; Adverse event; RA; Treatment-emergent adverse event; subcutaneous challenge; C1INH; TEAE; Hereditary angioedema; intradermal testing; BAT; intracutaneous test; skin prick test; rhC1INH; ICT
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2016.04.019

Background Recombinant human C1 inhibitor (rhC1INH) for on-demand treatment of hereditary angioedema is purified from milk of transgenic rabbits. It contains low amounts (<0.002%) of host-related impurities, which could trigger hypersensitivity reactions in patients with rabbit allergy (RA) and/or cow's milk allergy (CMA). Objective This study is an assessment of allergenicity and safety of rhC1INH in patients with RA and/or CMA. Methods Patients with CMA and/or RA underwent skin prick test (SPT), intracutaneous test (ICT), and, when results for both were negative, subcutaneous (SC) challenge with up to 2100U (14 mL) rhC1INH. The negative predictive value of the skin test protocol was calculated, defined as the ratio of patients without systemic symptoms of hypersensitivity following SC challenge, over the number of patients having tested negative for both the SPT and the ICT. Adverse events after exposure to rhC1INH were recorded. Results Twenty-six patients with RA and/or CMA were enrolled. Twenty-four had negative SPT and ICT results for rhC1INH, whereas 2 had negative SPT result but positive ICT result to rhC1INH (only the highest concentration). Twenty-two patients with negative SPT and ICT results underwent SC challenge. None developed allergic symptoms. Local treatment-emergent adverse events occurred in 7 patients (32%) after SC challenge. In 5 these were considered drug related. All were mild. Conclusions None of the patients with negative SPT and ICT results for rhC1INH had allergic symptoms during rhC1INH challenge. The negative predictive value of the combination of SPT and ICT for the outcome of the SC challenge was 100% (95% CI, 84.6%-100%). SC administration of rhC1INH was well tolerated.