Abstract

BackgroundThis is a retrospective review of the Winnipeg Regional Health Authority’s (WRHA) angioedema patients who were dispensed icatibant in hospital. Icatibant is a bradykinin B2 receptor antagonist indicated for Hereditary Angioedema (HAE) types I and II and is used off-label for HAE with normal C1INH (HAE-nC1INH) and ACE-inhibitor induced angioedema (ACEIIAE). The WRHA’s use of icatibant is regulated by the Allergist on call. We characterized icatibant's use and the timeline from patient presentation, compared the real-world experience with the FAST-3 trial and hypothesized the factors which may affect response to icatibant.MethodsBackground data were collected on patients. Angioedema attack-related data included administered medications, performed investigations and the timeline to endpoints such as onset of symptom relief. Data was analyzed in R with the package “survival.” Time-to-event data was analyzed using the Peto–Peto Prentice method or Mann–Whitney U-test. Data was also compared with published clinical trial data using the Sign Test. Fisher’s Exact Test was used to produce descriptive statistics.ResultsOverall, 21 patients accounted for 23 angioedema attacks treated with icatibant. Approximately half the patients had a diagnosis of HAE-nC1IHN and half of ACEIIAE. Of those presenting with angioedema, 65% were first treated with conventional medication. Patients without a prior angioedema diagnosis were evaluated only 40–50% of the time for C4 levels or C1INH function or level. The median time from patients’ arrival to the emergency department until the Allergy consultant’s response was 1.77 h. Patients with HAE-nC1IHN had median times to onset of symptom relief and final clinical outcome (1.13 h, p = 0.34; 3.50 h, p = 0.11) similar to those reported in FAST-3 for HAE I/II. Patients with ACEIIAE had longer median times to onset of symptom relief (4.86 h, p = 0.01) than predicted.ConclusionsHAE-nC1INH may be an appropriate indication for treatment with icatibant. Conversely, the results of this study do not support the use of icatibant for the treatment of ACEIIAE, concordant with a growing body of literature. Patients should be stratified into groups of more- or less-likely icatibant-responders through history and laboratory investigations in order to prevent potential delays.

Highlights

  • Introduction and backgroundIcatibant is a selective bradykinin B2 receptor antagonist that is used to treat bradykinin-mediated angioedema

  • This decision was driven by the conclusions of an Randomized controlled trial (RCT) published in 2015 that showed icatibant to be effective in reducing the time to complete resolution of ACE-inhibitor induced angioedema (ACEIIAE) [2]

  • The evidence supporting the use of icatibant for ACEIIAE is controversial, along with its use in other angioedema tentatively hypothesized to arise from the bradykinin-mediated pathway or supported by small case series [10,11,12]

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Summary

Introduction

Introduction and backgroundIcatibant is a selective bradykinin B2 receptor antagonist that is used to treat bradykinin-mediated angioedema. Since 2015, icatibant has been introduced to the WRHA formulary in the form of three doses at Winnipeg Health Sciences Center (HSC): this is the first inclusion of this drug in a Canadian center’s formulary This decision was driven by the conclusions of an RCT published in 2015 that showed icatibant to be effective in reducing the time to complete resolution of ACEIIAE [2]. The evidence supporting the use of icatibant for ACEIIAE is controversial, along with its use in other angioedema tentatively hypothesized to arise from the bradykinin-mediated pathway or supported by small case series (e.g. tPA mediated, acquired and idiopathic angioedema) [10,11,12] This is a retrospective review of the Winnipeg Regional Health Authority’s (WRHA) angioedema patients who were dispensed icatibant in hospital. We characterized icatibant’s use and the timeline from patient presentation, compared the real-world experience with the FAST-3 trial and hypothesized the factors which may affect response to icatibant

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Conclusion

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