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Use of recombinant C1 inhibitor in patients with resistant or frequent attacks of hereditary or acquired angioedema

  • Therapy
  • Published:
European Journal of Dermatology

Abstract

Background

Conestat alfa (Ruconest, rhC1INH) is the first recombinant human C1 inhibitor protein (C1INH) for the treatment of acute attacks of hereditary angioedema (HAE).

Objective

To assess clinical experience of the first 11 adult patients who received rhC1INH in clinical practice in the UK.

Methods

Eleven patients (nine HAE type 1, one HAE type 2 and one acquired angioedema with C1 inhibitor deficiency) received between one and six, mostly self-administered, doses of rhC1INH for acute HAE attacks. They were asked to record their time to first response and complete resolution following the treatment. This cohort included our most severely affected and difficult to treat patients.

Results

In most cases, time to first improvement following rhC1INH and complete resolution was recorded as comparable to their typical response to pdC1INH, although 4/11 patients reported that the time to first improvement was much quicker than their average pdC1INH response. Five of the 11 patients continued with rhC1INH as their preferred rescue treatment. Of those who chose not to continue the treatment, four reported a recurrence or early return of symptoms with rhC1INH.

Conclusion

In our experience, rhC1INH is a beneficial treatment for patients with preference for a C1INH that is not plasma derived and it is suitable for home treatment. In some cases it demonstrates cost saving, especially for heavier patients who require higher doses. In some patients rhC1INH may result in faster resolution of symptoms. It may be associated with an early return of symptoms in patients with exceptionally frequent attacks.

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References

  1. Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med 2008; 359: 1027–1036.

    Article  CAS  PubMed  Google Scholar 

  2. Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol 2012; 130: 692–697.

    Article  PubMed  Google Scholar 

  3. Bork K, Meng G, Staubach P, Hardt J. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med 2006; 119: 267–274.

    Article  PubMed  Google Scholar 

  4. Nzeako UC, Frigas E, Tremaine WJ. Hereditary angioedema: a broad review for clinicians. Arch Intern Med 2001; 161: 2417–2429.

    Article  CAS  PubMed  Google Scholar 

  5. Agostoni A, Cicardi M. Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients. Medicine (Baltimore) 1992; 71: 206–215.

    Article  CAS  Google Scholar 

  6. Longhurst H, Cicardi M. Hereditary angio-oedema. Lancet 2012; 379: 474–481.

    Article  PubMed  Google Scholar 

  7. Cugno M, Nussberger J, Cicardi M, Agostoni A. Bradykinin and the pathophysiology of angioedema. Int Immunopharmacol 2003; 3: 311–317.

    Article  CAS  PubMed  Google Scholar 

  8. Longhurst HJ, Farkas H, Craig T, et al. HAE international home therapy consensus document. Allergy Asthma Clin Immunol 2010; 6: 22.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Cicardi M, Banerji A, Bracho F, et al. Icatibant, a new bradykininreceptor antagonist, in hereditary angioedema. N Engl J Med 2010; 363: 532–541.

    Article  CAS  PubMed  Google Scholar 

  10. Cicardi M, Levy RJ, McNeil DL, et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med 2010; 363: 523–531.

    Article  CAS  PubMed  Google Scholar 

  11. Craig TJ, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz D, Obtulowicz K, et al. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol 2009; 124: 801–808.

    Article  CAS  PubMed  Google Scholar 

  12. Zuraw BL, Busse PJ, White M, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med 2010; 363: 513–522.

    Article  CAS  PubMed  Google Scholar 

  13. Lock RJ, Gompels MM. C 1-inhibitor deficiencies (hereditary angioedema): where are we with therapies? Curr Allergy Asthma Rep 2007; 7: 264–269.

    Article  CAS  PubMed  Google Scholar 

  14. Longhurst H. Rhucin, a recombinant C1 inhibitor for the treatment of hereditary angioedema and cerebral ischemia. Curr Opin Investig Drugs 2008; 9: 310–323.

    CAS  PubMed  Google Scholar 

  15. van Veen HA, Koiter J, Vogelezang CJ, et al. Characterization of recombinant human C1 inhibitor secreted in milk of transgenic rabbits. J Biotechnol 2012; 162: 319–326.

    Article  PubMed  Google Scholar 

  16. Ruconest TM: Immunological assessments non-promotional educational materials for prescribers. 2010.

    Google Scholar 

  17. Hack CE, Mannesse M, Baboeram A, Oortwijn B, Relan A. Immunogenicity assessment of recombinant human c1-inhibitor: an integrated analysis of clinical studies. BioDrugs 2012; 26: 303–313.

    Article  CAS  PubMed  Google Scholar 

  18. Biovitrum SO. Ruconest 2100 U power for solution for injection. Summary of Product Characteristics (SPC). 2011.

    Google Scholar 

  19. Craig TJ, Levy RJ, Wasserman RL, et al. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol 2009; 124: 801–808.

    Article  CAS  PubMed  Google Scholar 

  20. Hack CE, Relan A, van Amersfoort ES, Cicardi M. Target levels of functional C1-inhibitor in hereditary angioedema. Allergy 2012; 67: 123–130.

    Article  CAS  PubMed  Google Scholar 

  21. Zuraw B, Cicardi M, Levy RJ et al. Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol 2010; 126: 821–7e14.

    Article  CAS  PubMed  Google Scholar 

  22. Moldovan D, Reshef A, Fabiani J, et al. Efficacy and safety of recombinant human C1-inhibitor for the treatment of attacks of hereditary angioedema: European open-label extension study. Clin Exp Allergy 2012; 42: 929–935.

    CAS  PubMed  Google Scholar 

  23. Riedl MA, Levy RJ, Suez D, et al. Efficacy and safety of recombinant C1 inhibitor for the treatment of hereditary angioedema attacks: a North American open-label study. Ann Allergy Asthma Immunol 2013; 110: 295–299.

    Article  CAS  PubMed  Google Scholar 

  24. Kusuma A, Relan A, Knulst AC et al. Clinical impact of peripheral attacks in hereditary angioedema patients. Am J Med 2012; 125: 937 e17–937e 24.

    Article  Google Scholar 

  25. Cicardi M, Zingale LC, Pappalardo E, Folcioni A, Agostoni A. Autoantibodies and lymphoproliferative diseases in acquired C1-inhibitor deficiencies. Medicine (Baltimore) 2003; 82: 274–281.

    Google Scholar 

  26. Levi M, Choi G, Picavet C, Hack CE. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency. J Allergy Clin Immunol 2006; 117: 904–908.

    Article  CAS  PubMed  Google Scholar 

  27. Cicardi M, Johnston DT. Hereditary and acquired complement component 1 esterase inhibitor deficiency: a review for the hematologist. Acta Haematol 2012; 127: 208–220.

    Article  CAS  PubMed  Google Scholar 

  28. Manson AL, Price A, Dempster J, et al. In pursuit of excellence: An Integrated Care Pathway for C1 Inhibitor Deficiency. Clin Exp Immunol 2013; 173: 1–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Bright P, Dempster J, Longhurst H. Successful treatment of acquired C1 inhibitor deficiency with icatibant. Clin Exp Dermatol 2010; 35: 553–554.

    Article  CAS  PubMed  Google Scholar 

  30. Liccardi G, Passalacqua G. Sensitization to rabbit allergens in Italy-a multicentre study in atopic subjects without occupational exposure. Int Arch Allergy Immunol 2006; 141: 295–299.

    Article  PubMed  Google Scholar 

  31. Hauert J, Patston PA, Schapira M. C1 inhibitor cross-linking by tissue transglutaminase. J Biol Chem 2000; 275: 14558–14562.

    Article  CAS  PubMed  Google Scholar 

  32. Patston PA, Gettins P, Beechem J, Schapira M. Mechanism of serpin action: evidence that C1 inhibitor functions as a suicide substrate. Biochemistry 1991; 30: 8876–8882.

    Article  CAS  PubMed  Google Scholar 

  33. Cicardi M, Zanichelli A. Acquired angioedema. Allergy Asthma Clin Immunol 2010; 6: 14.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Choi G, Soeters MR, Farkas H, et al. Recombinant human C1-inhibitor in the treatment of acute angioedema attacks. Transfusion 2007; 47: 1028–1032.

    Article  CAS  PubMed  Google Scholar 

  35. Farrell C, Hayes S, Relan A, van Amersfoort ES, Pijpstra R, Hack CE. Population pharmacokinetics of recombinant human C1-inhibitor in patients with hereditary angioedema. Br J Clin Pharmacol 2013.

    Google Scholar 

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Authors and Affiliations

  1. Department of Immunology, Barts Health NHS Trust, London, E1 2ES, UK

    Ania L. Manson, John Dempster, Sofia Grigoriadou, Matthew S. Buckland & Hilary J. Longhurst

Authors
  1. Ania L. Manson
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  2. John Dempster
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  3. Sofia Grigoriadou
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  4. Matthew S. Buckland
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  5. Hilary J. Longhurst
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Correspondence to Hilary J. Longhurst.

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Manson, A.L., Dempster, J., Grigoriadou, S. et al. Use of recombinant C1 inhibitor in patients with resistant or frequent attacks of hereditary or acquired angioedema. Eur J Dermatol 24, 28–34 (2014). https://doi.org/10.1684/ejd.2013.2252

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  • DOI: https://doi.org/10.1684/ejd.2013.2252

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