title: Treatment of hereditary angioedema with icatibant: efficacy in clinical trials versus effectiveness in the real-world setting.
abstract: Icatibant was efficacious and generally well tolerated for type I or II hereditary angioedema (HAE) attacks in adults in the phase III, randomized, placebo-controlled For Angioedema Subcutaneous Treatment (FAST)-3 trial. The Icatibant Outcome Survey (IOS) is an international, observational study assessing icatibant treatment of HAE attacks. We conducted a posthoc analysis to compare for the first time the treatment of HAE type I or II attacks in patients prescribed icatibant in real-world (IOS) versus controlled trial settings (FAST-3). In FAST-3, patients received icatibant administered by health care professionals (HCPs). In IOS, patients self-administered icatibant or were treated by HCPs. Median time to treatment, time to resolution (almost complete resolution [FAST-3] or complete resolution [IOS]), and attack duration in patients who were treated by an HCP were compared between IOS and FAST-3. Descriptive statistical methods compared nonlaryngeal attacks treated less than 12 hours from attack onset. Analysis included 102 patients (376 attacks) from IOS and 43 patients (43 attacks) from FAST-3 (controlled phase). All endpoints were significantly longer for patients in FAST-3 (HCP administration) versus IOS (HCP administration) (p < .001; all comparisons). For FAST-3 (HCP administered) versus IOS (HCP administered), median time from attack onset to treatment was 6.5 versus 2.0 hours, median time to symptom resolution was 8.0 versus 3.5 hours, and median attack duration was 16.9 versus 7.3 hours, respectively. For combined HCP and self-administration in IOS, these endpoints were 1.6, 4.4, and 7.8 hours, respectively. This posthoc analysis showed for the first time that type I and II HAE attacks were treated earlier with icatibant in a real-world versus a phase III setting, with a shortened time to symptom resolution and attack duration. ClinicalTrials.gov NCT00912093 (FAST-3); NCT01034969 (IOS).
authors.affiliation: Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
authors.forename: Hilary J
authors.initials: HJ
authors.lastname: Longhurst
authors.forename: Vincent
authors.initials: V
authors.lastname: Fabien
authors.forename: H Henry
authors.initials: HH
authors.lastname: Li
authors.forename: William R
authors.initials: WR
authors.lastname: Lumry
mesh_terms: D000293:Adolescent; D000328:Adult; D054179:Angioedemas, Hereditary / Q000175:diagnosis / Q000188:drug therapy*; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065094:Bradykinin B2 Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018450:Disease Progression; D006801:Humans; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; C065679:icatibant; D001920:Bradykinin