The Icatibant Outcome Survey: experience of hereditary angioedema management from six European countries

Abstract

Background: Hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) is a rare, potentially fatal, bradykinin-mediated disease. Icatibant is a bradykinin B2 receptor antagonist originally approved in 2008 in the European Union and 2011 in the United States as an acute therapy option for HAE attacks in adults.

Objective: To compare demographics, disease characteristics and treatment outcomes of icatibant-treated HAE attacks in patients with C1-INH-HAE enrolled in the Icatibant Outcome Survey across six European countries: Austria, France, Germany, Italy, Spain and the UK.

Methods: The Icatibant Outcome Survey [IOS; Shire, Zug, Switzerland (NCT01034969)] is an international observational study monitoring the safety and effectiveness of icatibant. Descriptive, retrospective analyses compared IOS country data derived during July 2009-April 2015.

Results: Overall, 481 patients with C1-INH-HAE provided demographic data. A significant difference across countries in age at onset (P = 0.003) and baseline attack frequency (P < 0.001) was found although no significant differences were found with respect to gender (majority female; P = 0.109), age at diagnosis (P = 0.182) or delay in diagnosis (P = 0.059). Icatibant was used to treat 1893 attacks in 325 patients with majority self-administration in all countries. Overall, significant differences (all P < 0.001) were found across countries in time to treatment [median 1.8 h; median range: 0.0 (Germany-Austria) to 4.4 (France) h], time to resolution [median 6.5 h; median range: 3 (Germany-Austria) to 12 (France) h] and attack duration [median 10.5 h; median range: 3.1 (Germany-Austria) to 18.5 (France) h].

Conclusion: These data form the first European cross-country comparison of disease characteristics and icatibant use in patients with C1-INH-HAE who are enrolled in IOS. International variation in icatibant practice and treatment outcomes across the six European countries assessed highlight the need to further investigate the range of country-specific parameters driving regional variations in icatibant use.

Figure 1

Baseline annual attack frequency. n indicates number of patients: France (n = 177), Spain (n = 80), Italy (n = 55), UK (n = 45), Germany–Austria (n = 90), overall (n = 447). Boxes indicate 25% interquartile range (IQR), median and 75% IQR. Overall comparison: P < 0.001. All pairwise country comparisons: P < 0.001, except for France vs. Spain (P = 0.377), Germany–Austria vs. Italy (P = 0.286), Germany–Austria vs. UK (P = 0.37) and Italy vs. UK (P = 0.83).

Figure 2

Attack severity (grouped). n indicates number of icatibant‐treated attacks: France (n = 275), UK (n = 335), Italy (n = 270), Spain (n = 258), Germany–Austria (n = 504), overall (n = 1642). Overall comparison: P < 0.001. All pairwise country comparisons: P < 0.001, except for Germany–Austria vs. Spain (P = 0.140). Very mild = very mild interference with daily activities; mild = mild interference with daily activities; moderate = moderate interference with daily activities and no other countermeasures required; severe = severe interference with daily activities and with or without other countermeasures; very severe = very severe interference with daily activities and other countermeasures required.

Figure 3

Mode of administration. n indicates number of attacks: UK (n = 335), Italy (n = 272), Germany–Austria (n = 506), France (n = 346), Spain (n = 282), overall (n = 1741). Overall comparison: P < 0.001. All pairwise country comparisons: P < 0.001, except for France vs. Spain (P = 0.130) and Italy vs. UK (P = 0.323).

Figure 4

Treatment outcomes. n indicates number of attacks: Germany–Austria (n = 112), UK (n = 171), Italy (n = 181), Spain (n = 67), France (n = 148), overall (n = 679). Boxes indicate 25% interquartile range (IQR), median and 75% IQR. For time to treatment, all comparisons: P < 0.008, except for France vs. Spain (P = 0.144) and Italy vs. Spain (P = 0.594). For time to resolution, all comparisons: P < 0.037, except for France vs. Spain (P = 0.271) and Italy vs. Spain (P = 0.584). For attack duration, all comparisons: P < 0.005, except for France vs. Spain (P = 0.115) and Italy vs. Spain (P = 0.517). Time to events were only calculated for attacks with complete data for time to administration, time to resolution and attack duration.

Figure 5

Treatment outcomes by mode of administration. n indicates number of attacks: Germany–Austria [self, n = 100; health care provider (HCP), n = 12], UK (self, n = 160; HCP, n = 11), Italy (self, n = 165; HCP, n = 16), Spain (self, n = 45; HCP, n = 21), France (self, n = 122; HCP, n = 19), overall (self, n = 592; HCP, n = 79); Boxes indicate 25% interquartile range (IQR), median and 75% IQR. For self‐administration time to treatment, all pairwise comparisons: P ≤ 0.047, except for France vs. Spain (P = 0.713) and Italy vs. Spain (P = 0.261). For time to resolution, all pairwise comparisons: P < 0.049, except for France vs. Italy (P = 0.060), France vs. Spain (P = 0.722) and Italy vs. Spain (P = 0.064). For attack duration, all pairwise comparisons: P < 0.001, except for France vs. Spain (P = 0.894) and Italy vs. Spain (P = 0.053). For HCP administration: time to treatment all pairwise comparisons P ≥ 0.051 except for France vs. Spain (P = 0.043) and Italy vs. UK (P = 0.028). For time to resolution, all pairwise comparisons: P ≥ 0.052. For attack duration, all pairwise comparisons: P < 0.028, except for France vs. Germany–Austria (P = 0.216), France vs. UK (P = 0.800), Germany–Austria vs. Italy (P = 0.335), Germany–Austria vs. Spain (P = 0.231), Germany–Austria vs. UK (P = 0.274) and Italy vs. Spain (P = 0.738). Time to events were only calculated for attacks with complete data for time to administration, time to resolution and attack duration.