title: Recombinant human-C1 inhibitor is effective and safe for repeat hereditary angioedema attacks.
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.
authors: Institute for Asthma and Allergy, P.C., Chevy Chase, Md. Electronic address: hl@allergyasthma.us.
authors: H Henry
authors: HH
authors: Li
authors: University of Medicine and Pharmacy, Tirgu Mures, Romania.
authors: Dumitru
authors: D
authors: Moldovan
authors: University of Cincinnati, Cincinnati, Ohio.
authors: Jonathan A
authors: JA
authors: Bernstein
authors: Tel Aviv University, Sheba Medical Center, Tel-Hashomer, Israel.
authors: Avner
authors: A
authors: Reshef
authors: Faculty of Medicine, Department of Clinical and Environmental Allergology, Jagiellonian University, Krakow, Poland.
authors: Gregor
authors: G
authors: Porebski
authors: Faculty of Medicine, Department of Clinical and Environmental Allergology, Jagiellonian University, Krakow, Poland.
authors: Marcin
authors: M
authors: Stobiecki
authors: Baker Allergy Asthma Dermatology, Lake Oswego, Ore.
authors: James
authors: J
authors: Baker
authors: Family Allergy & Asthma Center, Atlanta, Ga.
authors: Robyn
authors: R
authors: Levy
authors: Pharming Technologies BV, Leiden, The Netherlands.
authors: Anurag
authors: A
authors: Relan
authors: UCSD School of Medicine, La Jolla, Calif.
authors: Marc
authors: M
authors: Riedl
mesh_terms: D000328:Adult; D054179:Angioedemas, Hereditary / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D050718:Complement C1 Inhibitor Protein; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007557:Israel; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D011994:Recombinant Proteins; C469952:SERPING1 protein, human
keywords: Hereditary angioedema; Recombinant human C1 esterase inhibitor; Repeat attacks