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 Jun;42(6):929-35. doi: 10.1111/j.1365-2222.2012.03984.x.

Abstract

Background: Hereditary angioedema (HAE) owing to C1 inhibitor deficiency is an autosomal dominant disorder, characterized by recurrent, potentially life-threatening, localized attacks of tissue swelling. Current treatment involves the infusion of C1 inhibitor protein (C1-INH) isolated from human plasma.

Objectives: This open-label extension to a European, Israeli and Argentinean randomized study (NCT00262301) aimed to investigate the efficacy and safety of recombinant human C1 inhibitor (rhC1-INH) as a first-line treatment following an HAE attack, together with its effect on subsequent attacks.

Methods: An HAE-specific visual analogue scale (VAS) 0-100 mm was used by patients to assess the severity of attack at four anatomical locations. Patients were treated with one, single-vial, fixed-dose of rhC1-INH (2100 U), followed by up to two further vials at the investigators discretion. The primary end-point was the time from first rhC1-INH injection to first onset of relief of symptoms (≥ 20 mm decrease on VAS). Response to treatment was defined as the onset of relief within 4 h.

Results: A total of 57 patients were treated for 194 HAE attacks. Overall, sustained relief of symptoms was achieved in 87% of rhC1-INH-treated patients within 4 h of treatment, with 57% of attacks requiring only one vial of rhC1-INH. When categorized by successive attacks experienced by individual patients, the response rate to rhC1-INH treatment was 96%, 83%, 87%, 80% and 80% for attacks 1-5 respectively. Treatment with rhC1-INH was well tolerated, with no discontinuations owing to treatment-emergent adverse events and no adverse events relating to immunogenicity.

Conclusions and clinical relevance: Treatment with rhC1-INH provides fast-onset relief for an HAE attack, with a high rate of therapeutic response maintained throughout subsequent attacks.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Angioedemas, Hereditary / drug therapy*
  • Complement C1 Inhibitor Protein / administration & dosage
  • Complement C1 Inhibitor Protein / adverse effects
  • Complement C1 Inhibitor Protein / therapeutic use*
  • Complement Inactivating Agents / administration & dosage
  • Complement Inactivating Agents / adverse effects
  • Complement Inactivating Agents / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Recombinant Proteins / therapeutic use
  • Risk Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Complement C1 Inhibitor Protein
  • Complement Inactivating Agents
  • Recombinant Proteins

Associated data

  • ClinicalTrials.gov/NCT00262301