Continued icatibant use across recurrent attacks in adolescents with hereditary angioedema.
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ABSTRACT:
SUBMITTER: Farkas H
PROVIDER: S-EPMC8453719 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
Publications
Continued icatibant use across recurrent attacks in adolescents with hereditary angioedema.
Farkas Henriette H Reshef Avner A Caballero Teresa T Ortega López María C MC Kessel Aharon A Vardi Moshe M Hao James J Aberer Werner W
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 20210511 6
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Project description:BackgroundAttacks of hereditary angioedema (HAE) are unpredictable and, if affecting the upper airway, can be lethal. Icatibant is used for physician- or patient self-administered symptomatic treatment of HAE attacks in adults. Its mode of action includes disruption of the bradykinin pathway via blockade of the bradykinin B(2) receptor. Early treatment is believed to shorten attack duration and prevent severe outcomes; however, evidence to support these benefits is lacking.ObjectiveTo examine the impact of timing of icatibant administration on the duration and resolution of HAE type I and II attacks.MethodsThe Icatibant Outcome Survey is an international, prospective, observational study for patients treated with icatibant. Data on timings and outcomes of icatibant treatment for HAE attacks were collected between July 2009-February 2012. A mixed-model of repeated measures was performed for 426 attacks in 136 HAE type I and II patients.ResultsAttack duration was significantly shorter in patients treated <1 hour of attack onset compared with those treated ≥ 1 hour (6.1 hours versus 16.8 hours [p<0.001]). Similar significant effects were observed for <2 hours versus ≥ 2 hours (7.2 hours versus 20.2 hours [p<0.001]) and <5 hours versus ≥ 5 hours (8.0 hours versus 23.5 hours [p<0.001]). Treatment within 1 hour of attack onset also significantly reduced time to attack resolution (5.8 hours versus 8.8 hours [p<0.05]). Self-administrators were more likely to treat early and experience shorter attacks than those treated by a healthcare professional.ConclusionEarly blockade of the bradykinin B(2) receptor with icatibant, particularly within the first hour of attack onset, significantly reduced attack duration and time to attack resolution.
| S-EPMC3563637 | biostudies-literature
Project description:BackgroundPatients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long-term prophylaxis (LTP), breakthrough attacks are known to occur. We used data from the Icatibant Outcome Survey (IOS) to evaluate the characteristics of breakthrough attacks and the effectiveness of icatibant as a treatment option.MethodsData on LTP use, attacks, and treatments were recorded. Attack characteristics, treatment characteristics, and outcomes (time to treatment, time to resolution, and duration of attack) were compared for attacks that occurred with versus without LTP.ResultsData on 3228 icatibant-treated attacks from 448 patients with C1-INH-HAE were analyzed; 30.1% of attacks occurred while patients were using LTP. Attack rate, attack severity, and the distribution of attack sites were similar across all types of LTP used, and were comparable to the results found in patients who did not receive LTP. Attacks were successfully treated with icatibant; 82.5% of all breakthrough attacks were treated with a single icatibant injection without C1-INH rescue medication. Treatment outcomes were comparable for breakthrough attacks across all LTP types, and for attacks without LTP.ConclusionsPatients who use LTP should be aware that breakthrough attacks can occur, and such attacks can be severe. Thus, patients with C1-INH-HAE using LTP should have emergency treatment readily available. Data from IOS show that icatibant is effective for the treatment of breakthrough attacks. Trial Registration NCT01034969.
| S-EPMC5497380 | biostudies-literature
Project description: Not available
| S-EPMC4304129 | biostudies-literature
Project description:BackgroundIcatibant is a bradykinin B2-receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1-inhibitor deficiency. Treatment is not adjusted by body weight however the impact of body mass index (BMI) on the effectiveness of icatibant is not documented in the literature. We examined disease characteristics and icatibant treatment effectiveness in patients stratified by BMI in the Icatibant Outcome Survey, an ongoing, international, observational study monitoring the real-world safety and effectiveness of icatibant.MethodsAttack and treatment characteristics as well as outcomes following treatment with icatibant were compared among patients with underweight, normal, overweight, and obese BMI.ResultsData from 2697 icatibant-treated attacks in 342 patients (3.5, 44.7, 34.8, and 17.0% patients of underweight, normal, overweight, and obese BMI, respectively) were analyzed. There was no significant difference in the frequency and severity of attacks across BMI groups, although obese patients tended to have more attacks of high severity. There was no impact of BMI on the frequency of laryngeal attacks, but patients with normal BMI had fewer cutaneous attacks and more abdominal attacks. Most attacks (71.9-83.8%) were treated with a single icatibant injection without the need for rescue with plasma-derived C1-inhibitor (pdC1-INH), regardless of BMI. Patients with obese BMI used pdC1-INH as rescue treatment more often (P < 0.0001; P = 0.0232 excluding 2 outliers) and treated attacks earlier than patients with normal BMI (P = 0.007). Furthermore, time to resolution and duration of attack were shorter for patients with high BMI (P < 0.001 for overweight and P < 0.05 for obese versus normal).ConclusionOverall, icatibant was comparatively effective in treating attacks in patients across all BMI groups.Trial registration NCT01034969.
| S-EPMC5870812 | biostudies-literature
Project description:BackgroundHereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.MethodsIn two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms.ResultsA total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported.ConclusionsIn patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
| S-EPMC4662377 | biostudies-literature
Project description:Hereditary angioedema (HAE) is an autosomal dominant, potentially life-threatening condition, manifesting as recurrent and self-limiting episodes of facial, laryngeal, genital, or peripheral swelling with abdominal pain secondary to intra-abdominal edema. The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000, without major sex or ethnic differences. Various treatment options for acute attacks and prophylaxis of HAE are authorized and available in the market, including plasma-derived (Berinert®, Cinryze®, and Cetor®) and recombinant (Rhucin® and Ruconest™) C1 inhibitors, kallikrein inhibitor-ecallantide (Kalbitor®), and bradykinin B2 receptor antagonist-icatibant (Firazyr®). Some of these drugs are used only to treat HAE attacks, whereas others are only approved for prophylactic therapies and all of them have improved disease outcomes due to their different mechanisms of action. Bradykinin and its binding to B2 receptor have been demonstrated to be responsible for most of the symptoms of HAE. Thus icatibant (Firazyr®), a bradykinin B2 receptor antagonist, has proven to be an effective and more targeted treatment option and has been approved for the treatment of acute attacks of HAE. Rapid and stable relief from symptoms of cutaneous, abdominal, or laryngeal HAE attacks has been demonstrated by 30 mg of icatibant in Phase III clinical trials. Self-resolving mild to moderate local site reactions after subcutaneous injection of icatibant were observed. Icatibant is a new, safe, and effective treatment for acute attacks of HAE. HAE has been reported to result in enormous humanistic burden to patients, affecting both physical and mental health, with a negative impact on education, career, and work productivity, and with substantial economic burdens. The timely and proper use of disease-specific treatments could improve patients' quality of life, reduce the disease-specific morbidity and mortality, and, last but not least, reduce costs associated with hospitalizations and emergency room visits. Therefore, the paradigm of HAE treatment has the potential to evolve significantly, thereby exponentially improving a patient's quality of life.
| S-EPMC3647445 | biostudies-other
Project description:IntroductionIcatibant, a first-in-class B2 bradykinin receptor antagonist, appears to have a favorable efficacy and safety profile for the treatment of acute attacks of hereditary angioedema in adults.AimsTo update the evidence and provide an overview of the available data on icatibant.Evidence reviewPeer reviewed articles published and listed in Medline Search and published updated guidelines for the treatment of acute attacks in hereditary angioedema type I and II in adults were reviewed. The validity and quality of evidence were evaluated.Place in therapyClinical evidence for the treatment of acute hereditary angioedema attacks with icatibant is strong. Approximately 10% of the patients require a second dose. No serious adverse reactions have been reported. The only significant side effects consistently registered by 90% of patients are transient local pain, swelling, and erythema at the local injection site.ConclusionSubcutaneously administered 30 mg icatibant has been shown to be a safe and efficacious treatment in clinical trials. It is the only specific treatment authorized for self-administration by the subcutaneous route offering increased patient independence.
| S-EPMC3467996 | biostudies-literature
Project description:Hereditary Angioedema (HAE) due to C1-inhibitor deficiency is a lifelong illness characterized by recurrent acute attacks of localized edema. Next to the identified role of dys-regulation in the kallikrein/bradykinin pathway at endothelial cell level, the involvement of circulating leucocytes (PBMC) in acute attacks is not yet clarified. To gain further insight into this process, we performed a PBMC microarray gene expression analysis on RNA isolated from patients with HAE comparing the transcriptome profile of acute attack with the remission phase.
2018-06-07 | E-MTAB-5897 | biostudies-arrayexpress
Project description:Hereditary angioedema (HAE) is a debilitating condition caused by a functional C1-inhibitor (C1-INH) deficiency and characterized clinically by episodes of subcutaneous or submucosal swelling. C1-INH replacement is highly effective for preventing HAE attacks and can improve health-related quality of life. Once available only for intravenous use, C1-INH is now available as a subcutaneous formulation for self-administration, shown to provide sustained plasma levels of C1-INH and reducing the monthly median HAE attack rate by 95% versus placebo in the phase 3 COMPACT study. Subcutaneously administered C1-INH satisfies multiple unmet needs in the management of patients with HAE.
| S-EPMC7328861 | biostudies-literature
Project description: Not available
| S-EPMC10092815 | biostudies-literature