PMID- 27321437 OWN - NLM STAT- MEDLINE DCOM- 20170615 LR - 20180824 IS - 1097-6825 (Electronic) IS - 0091-6749 (Linking) VI - 138 IP - 2 DP - 2016 Aug TI - Allergenicity and safety of recombinant human C1 esterase inhibitor in patients with allergy to rabbit or cow's milk. PG - 476-481.e1 LID - S0091-6749(16)30280-9 [pii] LID - 10.1016/j.jaci.2016.04.019 [doi] AB - 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. CI - Copyright (c) 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. FAU - van den Elzen, Mignon T AU - van den Elzen MT AD - Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: melzen3@umcutrecht.nl. FAU - van Os-Medendorp, Harmieke AU - van Os-Medendorp H AD - Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Rockmann-Helmbach, Heike AU - Rockmann-Helmbach H AD - Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - van Hoffen, Els AU - van Hoffen E AD - Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Lebens, Ans F M AU - Lebens AF AD - Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - van Doorn, Helma AU - van Doorn H AD - Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Klemans, Rob J B AU - Klemans RJ AD - Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Bruijnzeel-Koomen, Carla A F M AU - Bruijnzeel-Koomen CA AD - Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Hack, C Erik AU - Hack CE AD - Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Kaufman, Leonard AU - Kaufman L AD - DICE NV, Brussels, Belgium. FAU - Relan, Anurag AU - Relan A AD - Pharming Technologies BV, Leiden, The Netherlands. FAU - Knulst, Andre C AU - Knulst AC AD - Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160513 PL - United States TA - J Allergy Clin Immunol JT - The Journal of allergy and clinical immunology JID - 1275002 RN - 0 (Complement C1 Inhibitor Protein) RN - 0 (Recombinant Proteins) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Adult MH - Angioedemas, Hereditary/*complications/drug therapy MH - Animals MH - Cattle MH - Complement C1 Inhibitor Protein/*adverse effects/therapeutic use MH - Female MH - Humans MH - Immunoglobulin E/immunology MH - Male MH - Middle Aged MH - Milk/*adverse effects MH - Milk Hypersensitivity/*complications/diagnosis/*immunology MH - Phenotype MH - Rabbits MH - Recombinant Proteins/*adverse effects/therapeutic use MH - Severity of Illness Index MH - Skin Tests MH - Young Adult OTO - NOTNLM OT - Hereditary angioedema OT - allergenicity OT - cow's milk allergy OT - intracutaneous test OT - intradermal testing OT - rabbit allergy OT - recombinant human C1 esterase inhibitor OT - skin prick test OT - subcutaneous administration OT - subcutaneous challenge EDAT- 2016/06/21 06:00 MHDA- 2017/06/16 06:00 CRDT- 2016/06/21 06:00 PHST- 2016/02/09 00:00 [received] PHST- 2016/04/18 00:00 [revised] PHST- 2016/04/29 00:00 [accepted] PHST- 2016/06/21 06:00 [entrez] PHST- 2016/06/21 06:00 [pubmed] PHST- 2017/06/16 06:00 [medline] AID - S0091-6749(16)30280-9 [pii] AID - 10.1016/j.jaci.2016.04.019 [doi] PST - ppublish SO - J Allergy Clin Immunol. 2016 Aug;138(2):476-481.e1. doi: 10.1016/j.jaci.2016.04.019. Epub 2016 May 13.