Background
Methods
Study design
Statistical analysis
Results
Patient characteristics
Characteristic | Underweight BMI | Normal BMI | Overweight BMI | Obese BMI |
---|---|---|---|---|
Patients, n (%) | 12 (3.5) | 153 (44.7) | 119 (34.8) | 58 (17.0) |
BMI (kg/m2)a | ||||
Mean ± SD | 18.0 ± 0.5 | 22.2 ± 1.8 | 26.9 ± 1.3 | 34.5 ± 4.1 |
Median (range) | 18.1 (16.7–18.4) | 22.4 (18.7–25.0) | 26.6 (25.0–29.8) | 33.3 (30.0–46.7) |
Sex, n (%) | ||||
Female | 11 (91.7) | 105 (68.6) | 60 (50.4) | 33 (56.9) |
Male | 1 (8.3) | 48 (31.4) | 59 (49.6) | 25 (43.1) |
Age at enrollment (years), n (%) | ||||
≥ 12 to < 18 | 1 (8.3) | 2 (1.3) | 1 (0.8) | 0 |
≥ 18 to < 30 | 8 (66.7) | 53 (34.6) | 24 (20.2) | 10 (17.2) |
≥ 30 to < 50 | 1 (8.3) | 66 (43.1) | 52 (43.7) | 27 (46.6) |
≥ 50 to < 65 | 1 (8.3) | 27 (17.6) | 30 (25.2) | 16 (27.6) |
≥ 65 | 1 (8.3) | 5 (3.3) | 12 (10.1) | 5 (8.6) |
Country, n (%) | ||||
Austria | 0 | 6 (3.9) | 3 (2.5) | 0 |
Brazil | 0 | 6 (3.9) | 7 (5.9) | 3 (5.2) |
Denmark | 0 | 0 | 1 (0.8) | 2 (3.4) |
France | 2 (16.7) | 45 (29.4) | 21 (17.6) | 8 (13.8) |
Germany | 2 (16.7) | 16 (10.5) | 16 (13.4) | 12 (20.7) |
Greece | 0 | 3 (2.0) | 3 (2.5) | 1 (1.7) |
Israel | 2 (16.7) | 20 (13.1) | 15 (12.6) | 6 (10.3) |
Italy | 1 (8.3) | 18 (11.8) | 14 (11.8) | 4 (6.9) |
Spain | 4 (33.3) | 20 (13.1) | 22 (18.5) | 8 (13.8) |
Sweden | 0 | 0 | 1 (0.8) | 0 |
United Kingdom | 1 (8.3) | 19 (12.4) | 16 (13.4) | 14 (24.1) |
Ongoing long-term prophylaxis, n (%) | ||||
n | 3 | 75 | 58 | 33 |
C1-INHb | 0 | 11 (14.7) | 11 (19.0) | 4 (12.1) |
Attenuated androgensb | 0 | 47 (62.7) | 44 (75.9) | 24 (72.7) |
Tranexamic acidb | 2 (66.7) | 24 (32.0) | 9 (15.5) | 11 (33.3) |
Otherb | 1 (33.3) | 8 (10.7) | 4 (6.9) | 3 (9.1) |
No. of icatibant-treated attacks during enrollment | 104 | 1314 | 829 | 450 |
No. of icatibant-treated attacks per patientc | ||||
Mean ± SD | 8.7 ± 13.5 | 8.6 ± 14.8 | 7.0 ± 11.3 | 7.8 ± 10.8 |
Median (range) | 4.0 (1–47) | 4.0 (1–101) | 3.0 (1–83) | 3.5 (1–57) |
Attack characteristics
Underweight BMI | Normal BMI | Overweight BMI | Obese BMI | |
---|---|---|---|---|
Baseline
| ||||
Average duration of attack (h) | ||||
n | 12 | 150 | 106 | 41 |
Mean ± SDa | 50.7 ± 22.9 | 40.5 ± 32.4 | 45.9 ± 31.5 | 44.4 ± 35.5 |
Median (range) | 48.0 (6–92) | 41.0 (0–140) | 48.0 (0–156) | 48.0 (0–120) |
Follow-up
| ||||
Average duration of attack (h) | ||||
n | 11 | 76 | 70 | 25 |
Mean ± SDa | 34.6 ± 21.6 | 39.7 ± 31.1 | 37.6 ± 30.6 | 44.2 ± 29.9 |
Median (range) | 36 (0–72) | 37.5 (0–144) | 28.7 (0–120) | 48.0 (0.3–120) |
Treatment characteristics
Underweight BMI | Normal BMI | Overweight BMI | Obese BMI | |
---|---|---|---|---|
Type of administration, n (%)a | ||||
n | 103 | 1261 | 792 | 415 |
HCP | 10 (9.7) | 367 (29.1) | 148 (18.7) | 67 (16.1) |
Self | 93 (90.3) | 894 (70.9) | 644 (81.3) | 348 (83.9) |
No. of icatibant injections per attacka | ||||
n | 103 | 1301 | 826 | 434 |
Mean ± SD | 1.0 ± 0.2 | 1.1 ± 0.3 | 1.1 ± 0.3 | 1.1 ± 0.4 |
Median (range) | 1 (1–3) | 1 (1–3) | 1 (1–3) | 1 (1–6) |
No. of icatibant injections per attack, n (%)a | ||||
n | 103 | 1301 | 826 | 434 |
1 | 91 (88.3) | 1090 (83.8) | 687 (83.2) | 312 (71.9) |
1 + C1-INH rescue medication | 9 (8.7) | 83 (6.4) | 85 (10.3) | 73 (16.8) |
2 | 2 (1.9) | 112 (8.6) | 48 (5.8) | 24 (5.6) |
2 + C1-INH rescue medication | 0 | 8 (0.6) | 5 (0.6) | 22 (5.1) |
3 | 1 (1.0) | 6 (0.5) | 1 (0.1) | 2 (0.5) |
3 + C1-INH rescue medication | 0 | 2 (0.2) | 0 | 0 |
6 | 0 | 0 | 0 | 1 (0.2)b |
C1-INH rescue medication, n (%) | ||||
n | 104 | 1314 | 829 | 450 |
No. of attacks used C1-INH rescue | 9 (8.7) | 101 (7.7)c | 90 (10.9) | 96 (21.3)c,d |
No. of patients used C1-INH rescue | 2 | 29 | 21 | 16 |
Treatment outcomes
Time to treatment | n | Underweight BMI | n | Normal BMI | n | Overweight BMI | n | Obese BMI |
---|---|---|---|---|---|---|---|---|
Mean ± SD time to resolution | ||||||||
0 to < 1 h | 6 | 15.6 ± 16.7 | 155 | 10.4 ± 12.5 | 148 | 7.9 ± 11.0 | 108 | 5.4 ± 9.5 |
≥ 1 h | 6 | 10.1 ± 8.4 | 253 | 15.0 ± 17.7 | 201 | 9.9 ± 12.4 | 106 | 15.0 ± 17.4 |
P value | n.a. | 0.078 | 0.001 | < 0.001 | ||||
0 to < 2 h | 6 | 15.6 ± 16.7 | 228 | 11.8 ± 13.5 | 193 | 8.4 ± 12.0 | 142 | 6.5 ± 10.1 |
≥ 2 h | 6 | 10.1 ± 8.4 | 180 | 15.0 ± 18.6 | 156 | 9.8 ± 11.6 | 72 | 17.5 ± 19.2 |
P value | n.a. | 0.734 | 0.011 | < 0.001 | ||||
Mean ± SD duration of attack | ||||||||
0 to < 1 h | 6 | 15.8 ± 16.7 | 155 | 10.7 ± 12.5 | 148 | 8.1 ± 11.0 | 108 | 5.6 ± 9.5 |
≥ 1 h | 6 | 18.7 ± 12.5 | 253 | 21.8 ± 22.0 | 201 | 14.8 ± 14.2 | 106 | 22.4 ± 20.8 |
P value | n.a. | < 0.001 | < 0.001 | < 0.001 | ||||
0 to < 2 h | 6 | 15.8 ± 16.7 | 228 | 12.3 ± 13.7 | 193 | 8.9 ± 12.1 | 142 | 6.9 ± 10.2 |
≥ 2 h | 6 | 18.7 ± 12.5 | 180 | 24.2 ± 23.8 | 156 | 15.8 ± 13.9 | 72 | 27.7 ± 22.1 |
P value | n.a. | < 0.001 | < 0.001 | < 0.001 |
Effect (numerator) | Odds ratio | 95% CI | P value |
---|---|---|---|
Univariate analysisb | |||
Attack frequency (≥ 10 attacks/year) | 2.48 | – | < 0.001 |
BMI (≥ 25 kg/m2) | 1.77 | – | 0.012 |
Type of administration (HCP) | 0.55 | – | 0.067 |
Country | < 0.0001c | ||
Multivariate analysisd | |||
Attack frequency (≥ 10 attacks/year)e | 2.89 | 1.36–6.14 | 0.0056 |
BMI (≥ 25 kg/m2)e | 1.71 | 1.06–2.79 | 0.0295 |
Effect (numerator) | Odds ratio | 95% CI | P value |
---|---|---|---|
Univariate analysisb | |||
BMI (≥ 25 kg/m2) | 1.52 | – | 0.072 |
C1-INH rescue medication (yes) | 0.66 | – | 0.097 |
Affected site: skin (yes) | 0.74 | – | 0.118 |
Type of administration (HCP) | 1.49 | – | 0.133 |
Time to first injection (≥ 1 h) | 0.78 | – | 0.142 |
Country | 0.019c | ||
Multivariate analysisd | |||
BMI (≥ 25 kg/m2) | 4.46 | 2.24–8.89 | < 0.0001 |
C1-INH rescue medication (yes) | 0.31 | 0.19–0.50 | < 0.0001 |
Affected site: skin (yes) | 0.65 | 0.43–1.00 | 0.049 |
Adverse events (AEs)
Underweight BMI (n = 18) | Normal BMI (n = 210) | Overweight BMI (n = 162) | Obese BMI (n = 73) | |
---|---|---|---|---|
No. of patients, no. of events | 3, 3 | 48, 101 | 33, 91 | 19, 53 |
AEs related to icatibant (no. of patients, no. of events)a | 0, 0 | 7, 24 | 6, 29 | 2, 5 |
General disorders and administration site conditions | 0, 0 | 5, 9 | 3, 11 | 1, 1 |
Vascular disorders | 0, 0 | 3, 5 | 3, 4 | 1, 3 |
Skin and subcutaneous tissue disorders | 0, 0 | 0, 0 | 2, 2 | 1, 1 |
Gastrointestinal disorders | 0, 0 | 2, 2 | 1, 3 | 0, 0 |
Nervous system disorders | 0, 0 | 1, 1 | 1, 2 | 0, 0 |
Investigations | 0, 0 | 2, 5 | 0, 0 | 0, 0 |
Serious AEs (no. of patients, no. of events) | 0, 0 | 20, 28 | 16, 32 | 11, 30 |
Serious AEs related to icatibant and (no. of patients, no. of events)b | 0, 0 | 0, 0 | 2, 3 | 0, 0 |
Skin and subcutaneous tissue disorders | ||||
Angioedema | 0, 0 | 0, 0 | 1, 1 | 0, 0 |
Gastrointestinal disorders | ||||
Gastritis | 0, 0 | 0, 0 | 1, 1 | 0, 0 |
Reflux esophagitis | 0, 0 | 0, 0 | 1, 1 | 0, 0 |