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

Malbrán, Alejandro; Riedl, Marc A.; Ritchie, Bruce; Smith, William B.; Yang, William H.; Banerji, Aleena; Hébert, Jacques; Gleich, Gerald J.; Hurewitz, David; Jacobson, Kraig W.; Bernstein, Jonathan A.; Khan, David A.; Kirkpatrick, Charles H.; Resnick, David; Li, H.; Romero, Diego S. Fernández; Lumry, William R.

doi:10.1111/cei.12358

Cited by 35 publications

(40 citation statements)

References 24 publications

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“…Again, this observation is consistent with the findings of the FAST-1 and FAST-2 OLE phases [9,10] and studies of other HAE medications [18,19]. …”

Section: Discussionsupporting

confidence: 91%

“…With this in mind, the use of icatibant for the acute treatment of multiple HAE attacks was evaluated in the open-label extension (OLE) phases of each of the phase 3 studies. The results of the FAST-1 and FAST-2 OLE phases have previously been published: both studies reported that the efficacy and safety profiles of icatibant remained consistent over the treatment of multiple attacks [9,10]. Here, we report data from the controlled and OLE phases of FAST-3 to further evaluate the efficacy and safety of icatibant for the repeated treatment of multiple HAE attacks at any location, and also specifically for multiple laryngeal attacks.…”

Section: Introductionmentioning

confidence: 84%

“…The median times to onset of primary symptom relief and almost complete symptom relief were 1.0-2.0 h and 4.8-55.0 h, respectively, for the first to tenth cutaneous and/or abdominal attacks in the OLE phase of FAST-1, and 1.3-3.9 h and 6.5-33.1 h for the first to fifth cutaneous and/or abdominal attacks in the controlled and OLE phases of FAST-2 [9,10]. Similarly, consistency of response over the repeated treatment of multiple attacks has also been reported with other HAE medications, including the kallikrein inhibitor ecallantide [15] and C1-esterase inhibitors [16,17].…”

Section: Discussionmentioning

confidence: 99%

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Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3

Lumry¹,

Farkas

Moldovan

et al. 2015

Int Arch Allergy Immunol

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Background: In randomized, controlled, double-blind, multicenter phase 3 studies, one icatibant injection was efficacious and generally well tolerated in patients with a single hereditary angioedema (HAE) attack. Here, the efficacy and safety of icatibant for multiple HAE attacks was evaluated across the controlled and open-label extension phases of the For Angioedema Subcutaneous Treatment (FAST)-3 study (NCT00912093). Methods: In the controlled phase, adults with HAE type I or II were randomized (1:1) to receive a single subcutaneous injection of icatibant 30 mg or placebo within 6 h of an attack becoming mild (laryngeal) or moderate (cutaneous/abdominal). Open-label icatibant was administered for severe laryngeal symptoms. In the open-label extension phase, patients could receive up to three icatibant injections per attack. Efficacy and safety were analyzed for the first five icatibant-treated attacks at any location (prospective analysis) and laryngeal attacks (post hoc analysis) across both phases. Efficacy outcomes were based on patient-reported symptom severity (visual analog scale). Results: In groups of patients with one to five icatibant-treated attacks at any location (n = 88), the median times to onset of symptom relief, onset of primary symptom relief and almost complete symptom relief were 1.9-2.1, 1.5-2.0 and 3.5-19.7 h, respectively. The same outcomes for laryngeal attacks (n = 25) were 1.0-2.0, 1.0-2.0 and 1.5-8.1 h, respectively. The most frequently reported adverse events were a worsening or recurrence of HAE attack, headache and nasopharyngitis. Two serious adverse events (arrhythmia and noncardiac chest pain) were considered to be related to icatibant. Conclusions: Icatibant was efficacious and generally well tolerated across multiple HAE attacks, including laryngeal attacks.

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“…Again, this observation is consistent with the findings of the FAST-1 and FAST-2 OLE phases [9,10] and studies of other HAE medications [18,19]. …”

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3

Lumry¹,

Farkas

Moldovan

et al. 2015

Int Arch Allergy Immunol

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“…To accomplish this task, empowering patients to self-administer home therapy is essential [29]. Table 1 summarizes current treatment options for the management of acute attacks [13,[30][31][32][33][34][35][36][37][38][39][40]. Strategies include increasing C1-INH plasma levels with plasma derived or recombinant C1-INH replacement therapy, inhibition of kallikrein and blockade of bradykinin 2 receptors.…”

Section: Current Therapies For C1-inh-haementioning

confidence: 99%

Recombinant Replacement Therapy for Hereditary Angioedema Due to C1 Inhibitor Deficiency

2015

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Hereditary angioedema is a rare genetic condition transmitted as an autosomal dominant trait and characterized most commonly by the production of either inadequate or nonfunctioning C1 esterase inhibitor (C1-INH), a blood protein that regulates proteases in the complement, fibrinolytic and contact systems. Patients with hereditary angioedema suffer from episodic, unpredictable manifestations of edema affecting multiple anatomical locations, including the GI tract, facial tissue, the upper airway, oropharynx, urogenital region and/or the arms and legs. A rational approach to treatment is replacement of C1-INH protein, to normalize the levels of C1-INH activity and halt the progression of the biochemical activation processes underlying the edema formation. Ruconest is a highly purified recombinant human C1-INH. This article will focus on the results of ten clinical studies demonstrating the efficacy and safety of Ruconest(®) (Pharming Group NV, Leiden, the Netherlands), which is now approved for use in Europe, Israel and the USA.

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“…Unusual adverse reactions reported with icatibant use include dizziness, headache, abdominal pain, fever, asthenia, and increased serum transaminases. Subsequent open-label studies confirmed safety and efficacy of icatibant [39][40][41]. Icatibant should be administered with caution in patients with acute ischemic heart disease or unstable angina pectoris since animal studies have shown that icatibant blocking the B2 receptor can decrease coronary blood flow with worsening of cardiac function [42].…”

Section: Bradykinin B2 Receptor Antagonistmentioning

confidence: 99%

The safety of treatments for angioedema with hereditary C1 inhibitor deficiency

Zanichelli

Andreoli

et al. 2015

Expert Opinion on Drug Safety

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

Cited by 35 publications

References 24 publications

Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3

Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3

Recombinant Replacement Therapy for Hereditary Angioedema Due to C1 Inhibitor Deficiency

The safety of treatments for angioedema with hereditary C1 inhibitor deficiency

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