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



This study is an assessment of allergenicity and safety of rhC1INH in patients with RA and/or CMA.



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.



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.



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.
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.
Mignon T
MT
van den Elzen
Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Harmieke
H
van Os-Medendorp
Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Heike
H
Röckmann-Helmbach
Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Els
E
van Hoffen
Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Ans F M
AF
Lebens
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Helma
H
van Doorn
Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Rob J B
RJ
Klemans
Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Carla A F M
CA
Bruijnzeel-Koomen
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
C Erik
CE
Hack
DICE NV, Brussels, Belgium.
Leonard
L
Kaufman
Pharming Technologies BV, Leiden, The Netherlands.
Anurag
A
Relan
Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
André C
AC
Knulst
D000328:Adult; D054179:Angioedemas, Hereditary / Q000150:complications* / Q000188:drug therapy; D000818:Animals; D002417:Cattle; D050718:Complement C1 Inhibitor Protein / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008892:Milk / Q000009:adverse effects*; D016269:Milk Hypersensitivity / Q000150:complications* / Q000175:diagnosis / Q000276:immunology*; D010641:Phenotype; D011817:Rabbits; D011994:Recombinant Proteins / Q000009:adverse effects* / Q000627:therapeutic use; D012720:Severity of Illness Index; D012882:Skin Tests; D055815:Young Adult
D050718:Complement C1 Inhibitor Protein; D011994:Recombinant Proteins; D007073:Immunoglobulin E
Hereditary angioedema; allergenicity; cow's milk allergy; intracutaneous test; intradermal testing; rabbit allergy; recombinant human C1 esterase inhibitor; skin prick test; subcutaneous administration; subcutaneous challenge