Characterization Of Hereditary Angioedema Attacks Requiring Reinjection Of Icatibant: Findings From The Icatibant Outcome Survey

Rationale Data from the Icatibant Outcome Survey (IOS; NCT01034969), an international registry monitoring the safety and effectiveness of icatibant for the acute treatment of C1-INH-HAE attacks, have shown that a minority of attacks (212/2672, 7.9%) required >1 dose of icatibant. To better understand reasons for icatibant reinjection we analyzed reinjection data from >4900 attacks collected in IOS. Methods IOS patient/attack characteristics collected between July 2009-July 2017 were compared using descriptive statistics. Factors predictive of reinjection were determined using logistic regression. Results Data from 4955 attacks in 526 patients (57.2% females) with C1-INH-HAE were analyzed. Approximately 90% of icatibant injections were self-administered. Most attacks (93.1%) were treated with a single icatibant injection. Of attacks that required icatibant reinjection, most (199/289 [68.9%]) were severe/very severe. Few laryngeal attacks (16/256 [6.3%]) required reinjection. Reinjection was significantly more likely for patients using long-term prophylaxis versus not (8.0% vs 6.3% respectively, P=0.023). Reinjection was significantly more likely for attacks of higher severity (odds ratio [95%CI] of 2.2 [1.6,3.1], P<0.0001) more likely, although not significantly, for patients based on lower BMI (<25kg/m2 vs ≥25kg/m2; 1.4 [0.9,2.3], P=0.1479). The second dose was administered >6 hours after the first dose in 163/195 (83.6%) attacks. Conclusions More than 90% of HAE attacks resolved with a single icatibant injection. The reinjection rate was higher for attacks with higher severity. Most patients reinjected >6 hours after the first dose, as recommended.