The Icatibant Outcome Survey: 10 years of experience with icatibant for patients with hereditary angioedema

Abstract

In patients with hereditary angioedema (HAE), bradykinin causes swelling episodes by activating bradykinin B 2 receptors. Icatibant, a selective bradykinin B 2 receptor antagonist, is approved for on-demand treatment of HAE attacks. The Icatibant Outcome Survey (IOS; NCT01034969) is an ongoing observational registry initiated in 2009 to monitor the effectiveness/safety of icatibant in routine clinical practice. As of March 2019, 549 patients with HAE type 1 or 2 from the IOS registry had been treated of 5995 total attacks. This article reviews data published from IOS over time which have demonstrated that the effectiveness of icatibant in a real-world setting is comparable to efficacy in clinical trials; one dose is effective for the majority of attacks; early treatment (facilitated by self-administration) leads to faster resolution and shorter attack duration; effectiveness/safety of icatibant has been shown across a broad range of patient subgroups, including children/adolescents and patients with HAE with normal C1 inhibitor levels; and tolerability has been demonstrated in patients aged ≥65 years. Additionally, this review highlights how IOS data have provided valuable insights into patients' diagnostic journeys and treatment behaviours across individual countries. Such findings have helped to inform clinical strategies and guidelines to optimise HAE management and limit disease burden. ing role in HAE nC1-INH clinical manifestations. 7,10 Research strides have led to the development/approval of eight agents to date, targeting various aspects of the kallikreinkinin pathway (approvals vary by country); sites of action of select agents are shown in Figure S1. 4 Given the pivotal role of bradykinin in mediating vascular permeability in HAE via activation of the bradykinin B 2 receptor, blockage of this receptor is an important therapeutic strategy. 8 Icatibant (Firazyr®, Takeda Pharmaceuticals USA, Inc.) is a potent and selective antagonist of the bradykinin B 2 receptor. 11Efficacy/safety of icatibant for acute attacks in patients with HAE-1/2 was demonstrated in three pivotal phase 3 randomised controlled trials with open-label extensions. [12][13][14][15][16] Briefly,

Drugs of the Kallikrein–Kinin System: An Overview

“…[51] ARC-F12 preclinical, halted? [52] Plasmin/tPA inhibitor 6 tranexamic acid approved, 2nd line prophylactic agent [53] Bradykinin B2R antagonists 8 peptide icatibant approved [54] NPA deucrictibant (PHA-022121, PHA-121) clinical trials [24,55] On the effector side, the BK B2R antagonists inhibit the vascular manifestations of HAE (Table 2, Figure 1). The injectable and rapidly cleared peptide antagonist icatibant is widely used to abort HAE attacks.…”

Hereditary Angioedema: Novel Molecules for Treatment of Acute Attacks and Long-Term Prophylaxis

“…All these drugs have a different pharmacodynamic profile (Figure 1) and have been proved effective in halting the evolution of HAE attacks, including laryngeal attacks, in RCT studies, thus accelerating the resolution of an attack and providing relief shortly after administration and complete resolution of the attack in a few hours after injection. Moreover, post-registration registries have shown a consistent effect on the repetitive use and safety of these drugs over a long period of time [17]. For short-term prophylaxis, the only approved drug is plasma-derived C1 inhibitor (Bering, CSL Behring; Cinryze, Takeda), which is generally administered intravenously shortly (1 h) before the procedure.…”