Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks

Timothy J. Craig, Robyn J. Levy, Richard L. Wasserman, Againdra K. Bewtra, David Hurewitz, Krystyna Obtułowicz, Avner Reshef, Bruce Ritchie, Dumitru Moldovan, Todor Shirov, Vesna Grivcheva-Panovska, Peter C. Kiessling, Heinz Otto Keinecke, Jonathan A. Bernstein

Research output: Contribution to journalArticle

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Abstract

Background: Hereditary angioedema caused by C1 esterase inhibitor deficiency is a rare disorder. Objective: To compare the efficacy of pasteurized C1 esterase inhibitor concentrate (Berinert, CSL Behring) at intravenous doses of 10 or 20 U/kg body weight with placebo in the treatment of single, acute abdominal or facial attacks in patients with hereditary angioedema. Methods: This was a randomized, double-blind, placebo-controlled study in 125 patients with type I or II hereditary angioedema. The primary outcome was time from start of treatment to onset of symptom relief. Secondary outcomes were time to complete resolution, proportion of patients with worsened intensity of angioedema symptoms between 2 and 4hours after treatment, and number of vomiting episodes within 4 hours. Results: Median time to onset of relief was significantly shorter with C1 esterase inhibitor concentrate at a dose of 20 U/kg than with placebo (0.5 vs 1.5 hours; P = .0025), whereas with 10 U/kg, the time to onset of relief was only slightly shorter than with placebo (1.2 vs 1.5 hours; P = .2731). Compared with placebo, the reduction in time to onset of relief was greatest for severe attacks (0.5 vs 13.5 hours). The secondary outcomes consistently supported the efficacy of the 20 U/kg dose. C1 esterase inhibitor concentrate was safe and well tolerated. No seroconversions were observed for HIV, hepatitis virus, or human B19 virus. Conclusion: C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief.

Original languageEnglish
Pages (from-to)801-808
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume124
Issue number4
DOIs
StatePublished - Oct 2009

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Complement C1 Inhibitor Protein
Hereditary Angioedemas
Placebos
Hereditary Angioedema Types I and II
Human Parvovirus B19
Angioedema
Hepatitis Viruses
Therapeutics
Vomiting
Body Weight
human SERPING1 protein
HIV

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Medicine(all)

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Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. / Craig, Timothy J.; Levy, Robyn J.; Wasserman, Richard L.; Bewtra, Againdra K.; Hurewitz, David; Obtułowicz, Krystyna; Reshef, Avner; Ritchie, Bruce; Moldovan, Dumitru; Shirov, Todor; Grivcheva-Panovska, Vesna; Kiessling, Peter C.; Keinecke, Heinz Otto; Bernstein, Jonathan A.

In: Journal of Allergy and Clinical Immunology, Vol. 124, No. 4, 10.2009, p. 801-808.

Research output: Contribution to journalArticle

Craig, TJ, Levy, RJ, Wasserman, RL, Bewtra, AK, Hurewitz, D, Obtułowicz, K, Reshef, A, Ritchie, B, Moldovan, D, Shirov, T, Grivcheva-Panovska, V, Kiessling, PC, Keinecke, HO & Bernstein, JA 2009, 'Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks', Journal of Allergy and Clinical Immunology, vol. 124, no. 4, pp. 801-808. https://doi.org/10.1016/j.jaci.2009.07.017
Craig, Timothy J. ; Levy, Robyn J. ; Wasserman, Richard L. ; Bewtra, Againdra K. ; Hurewitz, David ; Obtułowicz, Krystyna ; Reshef, Avner ; Ritchie, Bruce ; Moldovan, Dumitru ; Shirov, Todor ; Grivcheva-Panovska, Vesna ; Kiessling, Peter C. ; Keinecke, Heinz Otto ; Bernstein, Jonathan A. / Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. In: Journal of Allergy and Clinical Immunology. 2009 ; Vol. 124, No. 4. pp. 801-808.
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abstract = "Background: Hereditary angioedema caused by C1 esterase inhibitor deficiency is a rare disorder. Objective: To compare the efficacy of pasteurized C1 esterase inhibitor concentrate (Berinert, CSL Behring) at intravenous doses of 10 or 20 U/kg body weight with placebo in the treatment of single, acute abdominal or facial attacks in patients with hereditary angioedema. Methods: This was a randomized, double-blind, placebo-controlled study in 125 patients with type I or II hereditary angioedema. The primary outcome was time from start of treatment to onset of symptom relief. Secondary outcomes were time to complete resolution, proportion of patients with worsened intensity of angioedema symptoms between 2 and 4hours after treatment, and number of vomiting episodes within 4 hours. Results: Median time to onset of relief was significantly shorter with C1 esterase inhibitor concentrate at a dose of 20 U/kg than with placebo (0.5 vs 1.5 hours; P = .0025), whereas with 10 U/kg, the time to onset of relief was only slightly shorter than with placebo (1.2 vs 1.5 hours; P = .2731). Compared with placebo, the reduction in time to onset of relief was greatest for severe attacks (0.5 vs 13.5 hours). The secondary outcomes consistently supported the efficacy of the 20 U/kg dose. C1 esterase inhibitor concentrate was safe and well tolerated. No seroconversions were observed for HIV, hepatitis virus, or human B19 virus. Conclusion: C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief.",
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AU - Levy, Robyn J.

AU - Wasserman, Richard L.

AU - Bewtra, Againdra K.

AU - Hurewitz, David

AU - Obtułowicz, Krystyna

AU - Reshef, Avner

AU - Ritchie, Bruce

AU - Moldovan, Dumitru

AU - Shirov, Todor

AU - Grivcheva-Panovska, Vesna

AU - Kiessling, Peter C.

AU - Keinecke, Heinz Otto

AU - Bernstein, Jonathan A.

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N2 - Background: Hereditary angioedema caused by C1 esterase inhibitor deficiency is a rare disorder. Objective: To compare the efficacy of pasteurized C1 esterase inhibitor concentrate (Berinert, CSL Behring) at intravenous doses of 10 or 20 U/kg body weight with placebo in the treatment of single, acute abdominal or facial attacks in patients with hereditary angioedema. Methods: This was a randomized, double-blind, placebo-controlled study in 125 patients with type I or II hereditary angioedema. The primary outcome was time from start of treatment to onset of symptom relief. Secondary outcomes were time to complete resolution, proportion of patients with worsened intensity of angioedema symptoms between 2 and 4hours after treatment, and number of vomiting episodes within 4 hours. Results: Median time to onset of relief was significantly shorter with C1 esterase inhibitor concentrate at a dose of 20 U/kg than with placebo (0.5 vs 1.5 hours; P = .0025), whereas with 10 U/kg, the time to onset of relief was only slightly shorter than with placebo (1.2 vs 1.5 hours; P = .2731). Compared with placebo, the reduction in time to onset of relief was greatest for severe attacks (0.5 vs 13.5 hours). The secondary outcomes consistently supported the efficacy of the 20 U/kg dose. C1 esterase inhibitor concentrate was safe and well tolerated. No seroconversions were observed for HIV, hepatitis virus, or human B19 virus. Conclusion: C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief.

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