Real-world outcomes in hereditary angioedema: first experience from the Icatibant Outcome Survey in the United Kingdom

Hilary J Longhurst, John Dempster, Lorena Lorenzo, Matthew Buckland, Sofia Grigoriadou, Christine Symons, Claire Bethune, Vincent Fabien, Catherine Bangs, Tomaz Garcez, Hilary J Longhurst, John Dempster, Lorena Lorenzo, Matthew Buckland, Sofia Grigoriadou, Christine Symons, Claire Bethune, Vincent Fabien, Catherine Bangs, Tomaz Garcez

Abstract

Background: Hereditary angioedema (HAE) is a potentially life-threatening, bradykinin-mediated disease, often misdiagnosed and under-treated, with long diagnostic delays. There are limited real-world data on best-practice management of HAE in the UK.

Objectives: To characterize the clinical profile, management and outcomes of patients with HAE type I and II from three specialist centres in the UK using data from the Icatibant Outcome Survey (IOS; Shire, Zug, Switzerland), an international observational study monitoring safety and effectiveness of icatibant, a selective bradykinin B2 receptor antagonist.

Methods: We performed retrospective analyses of IOS data for patients with HAE type I and II from three centres in the UK and compared UK data with pooled IOS data from 10 countries (48 centres).

Results: Analyses included 73 UK and 579 non-UK patients with HAE type I or II. Median diagnostic delay was 6.2 and 5.9 years, respectively. Analysis of data collected from February 2008 to July 2016 included 286 icatibant-treated attacks in 58 UK patients and 2553 icatibant-treated attacks in 436 non-UK patients (median of 3.0 attacks per patient in both groups). More attacks were treated by icatibant self-administration in UK patients (95.8%) than in non-UK patients (86.8%, p < 0.001). Time to icatibant treatment, time to resolution and attack duration were not significantly different in the UK versus non-UK patients.

Conclusion: UK patients from the specialist centres studied report similar diagnostic delay and similar icatibant treatment outcomes to their non-UK counterparts. However, improvements in the timely diagnosis of HAE are still required.Trial registration ClinicalTrials.gov NCT01034969.

Keywords: Acquired angioedema; C1-inhibitor deficiency; Hereditary angioedema; Icatibant; Icatibant Outcome Survey.

Figures

Fig. 1
Fig. 1
Schematic of effectiveness measures used in the Icatibant Outcome Survey
Fig. 2
Fig. 2
Proportion of the UK and non-UK IOS patients with days of missed work or education prior to IOS entry and during the IOS observation period. For the UK and non-UK patients, respectively, n = 49 and n = 125 for the period before IOS entry and n = 51 and n = 201 for the IOS follow-up period. BL baseline (12 months prior to IOS entry), FU follow-up, IOS Icatibant Outcome Survey. aNon-UK countries are Austria, Brazil, Denmark, France, Germany, Greece, Israel, Italy, Spain and Sweden
Fig. 3
Fig. 3
Proportion of the UK and non-UK IOS patients hospitalized at baseline (prior to IOS entry) and during IOS observation. For the UK and non-UK patients, respectively, n = 68 and n = 367 for the period before IOS entry and n = 52 and n = 399 for the IOS follow-up period. BL baseline (12 months prior to IOS entry), FU follow-up, IOS Icatibant Outcome Survey. aNon-UK countries are Austria, Brazil, Denmark, France, Germany, Greece, Israel, Italy, Spain and Sweden
Fig. 4
Fig. 4
Proportion of HAE patients in the UK sample with a delay in diagnosis. HAE hereditary angioedema. n = 58
Fig. 5
Fig. 5
Proportion of HAE attacks treated with icatibant by self-administration or administration by HCPs per attack in the UK and non-UK patients. HAE hereditary angioedema, HCP healthcare professional
Fig. 6
Fig. 6
Administration of icatibant for first five HAE attacks in UK patients. HCP health care professional. aThe remaining two HCP-administered instances of icatibant occurred during attack 14 (9.1%) and attack 19 (11.1%). Family member administrations are included in the self-administration category. All non–self-administrations are included in the HCP category. Missing attack dates are not taken into account
Fig. 7
Fig. 7
Proportion of icatibant-treated HAE attacks (with complete data for time to treatment, time to resolution and attack duration) in UK patients and non-UK patients according to a time to treatment, b time to symptom resolution and c duration of attack. HAE hereditary angioedema, Time to treatment time between the start of the attack and the first icatibant injection, Time to resolution time between first injection of icatibant and complete resolution of symptoms, Attack duration time between start of attack and complete resolution of symptoms. aNon-UK countries are Austria, Brazil, Denmark, France, Germany, Greece, Israel, Italy, Spain and Sweden. bGeneralized linear model for repeated measures
Fig. 8
Fig. 8
Abdominal computed tomography image obtained at admission of a 47-year-old male patient with HAE type I with abdominal angioedema

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