Recombinant human-C1 inhibitor is effective and safe for repeat hereditary angioedema attacks

J Allergy Clin Immunol Pract. 2015 May-Jun;3(3):417-23. doi: 10.1016/j.jaip.2014.12.013. Epub 2015 Feb 11.

Abstract

Background: Hereditary angioedema (HAE) caused by a deficiency in functional C1 esterase inhibitor (C1INH) is characterized by recurrent episodes of cutaneous and/or mucosal/submucosal tissue swelling affecting multiple anatomic locations. Previous studies demonstrated efficacy of recombinant human C1INH (rhC1INH) for acute HAE attacks.

Objective: This study evaluated the efficacy and safety of rhC1INH (50 IU/kg) for the treatment of multiple HAE attacks in an open-label extension study.

Methods: Time to onset of symptom relief and time to minimal symptoms were assessed using a Treatment Effect Questionnaire (TEQ), a visual analog scale, and a 6-point ordinal scale Investigator Score.

Results: Forty-four patients received rhC1INH, and a single dose was administered for 215 of 224 (96%) attacks. Median time to beginning of symptom relief based on TEQ for the first 5 attacks was 75.0 (95% CI, 69-89) minutes, ranging from 62.5 (95% CI, 48-90) to 134.0 (95% CI, 32-119) minutes. Median time to minimal symptoms using TEQ for the first 3 attacks was 303.0 (95% CI, 211-367) minutes. rhC1INH was well tolerated. There were no discontinuations due to adverse events. No thrombotic or anaphylactic events were reported, and repeat rhC1INH treatments were not associated with neutralizing anti-C1INH antibodies.

Conclusions: A single 50-IU/kg dose rhC1INH was effective for improving symptoms of an HAE attack with sustained efficacy for treatment of subsequent attacks. rhC1INH had a positive safety profile throughout the study. This study supports repeated use of rhC1INH over time in patients with HAE attacks.

Keywords: Hereditary angioedema; Recombinant human C1 esterase inhibitor; Repeat attacks.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angioedemas, Hereditary / diagnosis
  • Angioedemas, Hereditary / drug therapy*
  • Angioedemas, Hereditary / immunology
  • Complement C1 Inactivator Proteins / administration & dosage
  • Complement C1 Inactivator Proteins / adverse effects
  • Complement C1 Inactivator Proteins / therapeutic use*
  • Complement C1 Inhibitor Protein
  • Drug Administration Schedule
  • Europe
  • Female
  • Humans
  • Injections, Intravenous
  • Israel
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Recombinant Proteins / therapeutic use
  • Remission Induction
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome
  • United States

Substances

  • Complement C1 Inactivator Proteins
  • Complement C1 Inhibitor Protein
  • Recombinant Proteins
  • SERPING1 protein, human

Associated data

  • IRCT/NCT01188564