Repeat treatment of acute hereditary angioedema attacks with open-label icatibant in the FAST-1 trial

Abstract

Hereditary angioedema (HAE) is characterized by potentially life-threatening recurrent episodes of oedema. The open-label extension (OLE) phase of the For Angioedema Subcutaneous Treatment (FAST)-1 trial (NCT00097695) evaluated the efficacy and safety of repeated icatibant exposure in adults with multiple HAE attacks. Following completion of the randomized, controlled phase, patients could receive open-label icatibant (30 mg subcutaneously) for subsequent attacks. The primary end-point was time to onset of primary symptom relief, as assessed by visual analogue scale (VAS). Descriptive statistics were reported for cutaneous/abdominal attacks 1-10 treated in the OLE phase and individual laryngeal attacks. Post-hoc analyses were conducted in patients with ≥ 5 attacks across the controlled and OLE phases. Safety was evaluated throughout. During the OLE phase, 72 patients received icatibant for 340 attacks. For cutaneous/abdominal attacks 1-10, the median time to onset of primary symptom relief was 1·0-2·0 h. For laryngeal attacks 1-12, patient-assessed median time to initial symptom improvement was 0·3-1·2 h. Post-hoc analyses showed the time to onset of symptom relief based on composite VAS was consistent across repeated treatments with icatibant. One injection of icatibant was sufficient to treat 88·2% of attacks; rescue medication was required in 5·3% of attacks. No icatibant-related serious adverse events were reported. Icatibant provided consistent efficacy and was well tolerated for repeated treatment of HAE attacks.

Keywords: C1-inhibitor deficiency; FAST-1; OLE phase; bradykinin B2 receptor antagonist; hereditary angioedema; icatibant.

Fig. 1

Post-hoc analyses of the proportion of patients achieving (a) onset of symptom relief^† (b) onset of symptom relief for the primary symptom^b and (c) almost complete symptom relief^c. The cohort of patients demonstrated here are from the post-hoc analyses of those treated for at least five attacks with icatibant during the controlled and open-label extension (OLE) phases of For Angioedema Subcutaneous Treatment (FAST-1). ^aOnset of symptom relief was defined as the first of three consecutive measures in which there was at least a 50% reduction from pretreatment in the three-symptom composite visual analogue scale (VAS) score. The median time to onset to onset is calculated using Kaplan–Meier methodology. ^bOnset of primary symptom relief was defined as the first of three consecutive measures in which there was a reduction less than 0·86 × baseline VAS value – 16 for a single primary VAS score, where the baseline VAS value was ≥30 mm. For abdominal attacks, the primary VAS score was defined as abdominal pain, and for cutaneous attacks as the more severe of either skin swelling or skin pain. The median time to onset is calculated using Kaplan–Meier methodology. ^cAlmost complete symptom relief was defined as the first of three consecutive measures in which all three symptoms scores were between 0 and 10 mm on the VAS scale. The median time to almost complete symptom relief was calculated using Kaplan–Meier methodology.

Fig. 2

Time to initial symptom improvement for laryngeal attacks. Each dot represents a patient's report of the time of initial symptom improvement. There were three instances in which the time to initial symptom improvement was missing: one each at attacks 1, 8 and 152. Patient numbers for each attack were as follows: attack 1, n = 6; attack 2, n = 6; attack 3, n = 2; attack 4, n = 3; attack 5, n = 5; attack 6, n = 2; attack 7, n = 2; attack 8, n = 2; attack 9, n = 2; attack 10, n = 2; attack 11, n = 3; attack 12, n = 1); attack 15, n = 1.

Fig. 3

Post-hoc analyses of the overall number of attacks requiring more than one icatibant injection.