Nanofiltered C1-Esterase Inhibitor for the Acute Management and Prevention of Hereditary Angioedema Attacks due to C1-Inhibitor Deficiency in Children

Lumry, William R.; Manning, M. A.; Hurewitz, David; Davis-Lorton, Mark; Fitts, David; Kalfus, Ira; Uknis, Marc E.

doi:10.1016/j.jpeds.2012.11.030

Cited by 55 publications

(59 citation statements)

References 22 publications

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“…An open-label 2.6-year extension study in patients with a mean (SD) age of 36.5 (16.5) years showed that C1-INH prophylaxis reduced the median number of monthly attacks by 93.7% (3.00-0.19) [24]. A post hoc analysis of data from 4 prospective clinical trials was performed to evaluate the efficacy of C1-INH (1,000 U) for acute treatment and prophylaxis in a pediatric subgroup [21]. This post hoc analysis showed that in the placebo-controlled trial, 4 patients (9-17 years of age) had their number of HAE attacks almost halved from 13.0 with placebo to 7.0 with C1-INH prophylaxis.…”

Section: Discussionmentioning

confidence: 99%

“…This post hoc analysis showed that in the placebo-controlled trial, 4 patients (9-17 years of age) had their number of HAE attacks almost halved from 13.0 with placebo to 7.0 with C1-INH prophylaxis. In addition, 23 patients aged 2-17 years in the open-label extension study [21] had a reduction in their median (range) monthly attacks from 3.0 (0.5-28.0) before enrollment to 0.39 (0-3.36) after prophylaxis. However, this was a post hoc analysis rather than a clinical trial in children with HAE.…”

Section: Discussionmentioning

confidence: 99%

“…It is administered intravenously to patients as a fixed dose rather than a body weight-adjusted dose of 1,000 U every 3-4 days in adolescents and adults and 500 U or 1,000 U if needed in pediatric patients. Previous studies including 2 placebo-controlled and 2 open-label extension studies involving 46 patients indicated that C1-INH is safe and efficacious in this group [21]. …”

Section: Introductionmentioning

confidence: 99%

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Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings

Aygören‐Pürsün

Soteres

Moldovan

et al. 2017

Int Arch Allergy Immunol

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Background: Hereditary angioedema (HAE) is a rare genetic disease causing unpredictable and potentially life-threatening subcutaneous and submucosal edematous attacks. Cinryze® (Shire ViroPharma Inc., Lexington, MA, USA), a nanofiltered C1 inhibitor (C1-INH), is approved in Europe for the treatment, preprocedure prevention, and routine prophylaxis of HAE attacks, and for the routine prophylaxis of attacks in the USA. This phase 3 study assessed the safety and efficacy of 2 C1-INH doses in preventing attacks in children aged 6-11 years. Methods: A randomized single-blind crossover study was initiated in March 2014. Results for the first 6 patients completing the study are reported here. After a 12-week qualifying observation period, patients were randomly assigned to 1 of 2 C1-INH doses, 500 or 1,000 U, every 3-4 days for 12 weeks and crossed over to the alternative dose for a second 12-week period. The primary efficacy endpoint was the number of angioedema attacks per month. Results: Six females with HAE type I and a median age of 10.5 years received 2 doses of C1-INH (500 and 1,000 U). The mean (SD) difference in the number of monthly angioedema attacks between the baseline observation period and the treatment period was -1.89 (1.31) with 500 U and -1.89 (1.11) with 1,000 U. During the treatment periods, cumulative attack severity, cumulative daily severity, and the number of attacks needing acute treatment were lower. No serious adverse events or study drug discontinuations occurred. Conclusions: Interim findings from this study indicate that routine prevention with intravenous administration of C1-INH is efficacious, safe, and well tolerated in children ≥6 years of age.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings

Aygören‐Pürsün

Soteres

Moldovan

et al. 2017

Int Arch Allergy Immunol

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“…[50]. Berinert ® , at 20 U/kg, has less risk of containing an infectious agent, is approved by the Food and Drug Administration (FDA) in children and is preferable when available [51][52][53].…”

Section: Us Consensus For the Management Of Children With C1-inh-haementioning

confidence: 99%

Short‐Term Prophylaxis in Odontostomatological, Maxillofacial and ENT Procedures in Patients with Hereditary Angioedema Due to C1‐Inhibitor Deficiency

Palomo¹,

Caballero²

2017

A Comprehensive Review of Urticaria and Angioedema

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Oestrogens, trauma, infections or stress has been described as triggers for angioedema (AE) attacks in patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). Microtrauma can precipitate the onset of acute AE attacks, and thus, dental-oral procedures carry a high risk of triggering them and also an increased risk of death from asphyxiation due to the AE location. In the past, without proper specific treatment, the overall mortality after dental surgery in patients with C1-INH-HAE was up to 30-40%. Some dental-oral, medical and/or surgical procedures are susceptible to receive "short-term prophylaxis" (STP) in order to reduce the risk of AE. We describe the published case reports of dental-oral, maxillofacial and ear, nose and throat (ENT) procedures in patients with C1-INH-HAE. Different consensus algorithms and clinical guidelines have been published for managing dental-oral, maxillofacial and otolaryngological procedures (DOMFOPs) and will be reviewed below. Based on the clinical experience of the Department of Allergology of the University Hospital La Paz (Madrid) and the University General Hospital Nuestra Señora del Prado (Talavera de la Reina), these algorithms have been updated and modified. We advise to classify procedures according to the risk of producing AE as minor, intermediate and major risks.

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“…Recent studies revealed that purified C1-inhibitor, which is approved in the United States for treatment of patients 12 and older, has efficacy and safety in children similar to that seen in adults. [7][8][9] Ecallantide is currently indicated for treatment of HAE patients 16 and older and icatibant for those 18 and older. We report here on experience with ecallantide for treatment of attacks in children and adolescents with HAE due to C1-INH deficiency.…”

mentioning

confidence: 99%

Use of Ecallantide in Pediatric Hereditary Angioedema

et al. 2013

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WHAT'S KNOWN ON THIS SUBJECT:Patients with hereditary angioedema (HAE) have recurrent episodes of painful swelling. Several new therapies to prevent and treat HAE attacks are approved by the Food and Drug Administration, but their safety and efficacy in children are largely unknown.WHAT THIS STUDY ADDS: Ecallantide appears effective for treatment of HAE attacks in pediatric patients age 10 to 17 years with an acceptable safety profile. It represents a potential treatment option for adolescents with HAE. abstract OBJECTIVE: Hereditary angioedema (HAE) due to C1-inhbitor deficiency is a rare autosomal dominant disease that manifests as sudden unpredictable attacks of subcutaneous or submucosal edema affecting the skin, intestine, and upper airway. Ecallantide is a plasma kallikrein inhibitor indicated for treatment of HAE attacks in patients aged 16 years and older. This analysis examines safety and efficacy of ecallantide for treatment of HAE attacks in patients ,18 years of age.METHODS: Data for patients aged 9 to 17 years treated subcutaneously with 30 mg ecallantide or placebo were pooled from 4 clinical studies (2 double-blind, placebo-controlled and 2 open-label). Efficacy end points included 2 HAE-specific patient-reported outcome measures: mean symptom complex severity (MSCS) score and treatment outcome score (TOS). Times to initial improvement, sustained improvement, and complete or near-complete symptom resolution were calculated. Treatment-emergent adverse events were examined. RESULTS:Overall, 29 pediatric patients were included; 25 of them received ecallantide for 62 total HAE attacks, and 10 received placebo for 10 total attacks. Ecallantide-treated attacks revealed clinically relevant reduction in symptom severity at 4 hours postdosing based on mean change in MSCS score (21.4 6 0.9 ecallantide versus 20.9 6 0.6 placebo) and TOS (73.9 6 35.50 ecallantide versus 45.0 6 43.78 placebo). Patients treated with ecallantide showed rapid improvement in symptoms (median time to complete or near-complete symptom resolution: 181 minutes). No serious adverse events related to treatment were observed.CONCLUSIONS: Ecallantide appears effective for HAE attacks in adolescents, with rapid symptom improvement. No unexpected safety issues were identified. Pediatrics 2013;132:e490-e497 AUTHORS:

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Nanofiltered C1-Esterase Inhibitor for the Acute Management and Prevention of Hereditary Angioedema Attacks due to C1-Inhibitor Deficiency in Children

Cited by 55 publications

References 22 publications

Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings

Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings

Short‐Term Prophylaxis in Odontostomatological, Maxillofacial and ENT Procedures in Patients with Hereditary Angioedema Due to C1‐Inhibitor Deficiency

Use of Ecallantide in Pediatric Hereditary Angioedema

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