Icatibant use in Brazilian patients with hereditary angioedema (HAE) type 1 or 2 and HAE with normal C1-INH levels: findings from the Icatibant Outcome Survey Registry Study

Abstract

Background: Hereditary angioedema can be caused by C1-Inhibitor (C1-INH) deficiency and/or dysfunction (HAE-1/2) or can occur in patients with normal C1-INH (HAE nC1-INH).

Methods: The Icatibant Outcome Survey (IOS; NCT01034969) registry monitors the safety and effectiveness of icatibant for treating acute angioedema.

Objective: Present findings from Brazilian patients with HAE-1/2 and HAE nC1-INH participating in IOS.

Results: 42 patients were enrolled (HAE-1/2, n = 26; HAE nC1-INH, n = 16). Median age at symptom onset was significantly lower with HAE-1/2 vs. HAE nC1-INH (10.0 vs. 16.5y, respectively; p = 0.0105), whereas median age at diagnosis (31.1 vs. 40.9y; p = 0.1276) and the median time between symptom onset and diagnosis (15.0 vs. 23.8y; p = 0.6680) were numerically lower vs. HAE nC1-INH, respectively. One icatibant dose was used for > 95% of HAE attacks. Median (range) time-to-event outcomes were shorter for patients with HAE nC1-INH vs. HAE-1/2, including time to first administration (0.5 [0-96.0] vs. 1.0 [0-94.0]h, respectively), time from first administration to complete resolution (1.0 [0-88.0] vs. 5.5 [0-96.0]h, respectively), and total attack duration (7.0 [0.3-99.0] vs. 18.5 [0.1-100.0]h, respectively). Mean (SD) time from attack onset to resolution was significantly shorter for patients with HAE nC1-INH vs. HAE-1/2 (9.8 [18.7] vs. 19.6 [24.0]h, respectively; p = 0.0174). 83 adverse events (AEs) in 42 patients were reported; most were mild (66.3%) or moderate (13.3%) and non-serious (75.9%). The most common icatibant-related AE was injection site erythema (HAE-1/2, 34.6%; HAE nC1-INH, 18.8%).

Study limitations: This was an observational study without a treatment comparator and that relied on patient recall.

Conclusions: Findings demonstrate effectiveness and tolerability of icatibant in Brazilian HAE patients.

Keywords: Bradykinin; Bradykinin receptor; Brazil; Hereditary angioedema.

Figure 1

Treatment-related time-to-event effectiveness outcomes. Adapted from: Maurer M, et al.. HAE, Hereditary Angioedema.

Figure 2

Baseline demographics. (a) Median age at hereditary angioedema symptom onset (p = 0.0105), (b) median age at diagnosis (p = 0.1276), and (c) median time from symptom onset to diagnosis (difference between age at first symptoms and age at diagnosis; p = 0.6680). The left and right edges of the boxes represent the 25th and 75th percentiles, respectively; box whiskers denote the minimum and maximum recorded values. HAE-1/2, Hereditary Angioedema with C1-inhibitor deficiency and/or dysfunction; HAE nC1-INH, Hereditary Angioedema with normal levels and function of C1-inhibitor.

Figure 3

Most common location of hereditary angioedema attacks. HAE-1/2, n = 164 attacks (one missing); HAE nC1-INH, n = 60 attacks (three missing). Only the most common single sites and combinations of sites are shown; thus, percentages do not total 100%. Attacks affecting the skin refer to the following locations: arms, ears, eyelids, face, feet, genitals, hands, legs, lips, nose, torso, other, unknown. Abdominal attacks refer specifically to attacks affecting the gastrointestinal mucosa. HAE-1/2, Hereditary Angioedema with C1-inhibitor deficiency and/or dysfunction; HAE nC1-INH, Hereditary Angioedema with normal levels and function of C1-inhibitor.

Figure 4

Severity of hereditary angioedema attacks prior to treatment. HAE-1/2, n = 164 attacks (one missing); HAE nC1-INH, n = 60 attacks (three missing). Attack severity was evaluated based on the following descriptions: 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. The difference between the two patient groups in the occurrence of mild/moderate vs. severe/very severe attacks was not significant (p = 0.1038). HAE-1/2, Hereditary Angioedema with C1-inhibitor deficiency and/or dysfunction; HAE nC1-INH, Hereditary Angioedema with normal levels and function of C1-inhibitor.

Figure 5

Time-to-event outcomes. The lower and upper edges of the boxes represent the 25th and 75th percentiles, respectively; box whiskers denote the minimum and maximum recorded values. HAE-1/2, Hereditary Angioedema type 1 or 2; HAE nC1-INH, Hereditary Angioedema with normal levels and function of C1-inhibitor; SD, Standard Deviation.