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

Aygören‐Pürsün, Emel; Soteres, D.; Moldovan, Dumitru; Christensen, Jim; Leerberghe, Arthur Van; Hao, James; Schranz, Jennifer; Jacobson, Kraig W.; Martinez‐Saguer, Inmaculada

doi:10.1159/000477541

Cited by 22 publications

(13 citation statements)

References 22 publications

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“…The study's safety findings are generally consistent with those in the interim analysis and with pediatric and adult subgroups in other C1‐INH studies …”

Section: Discussionsupporting

confidence: 83%

“…In this first blinded, randomized, controlled trial of C1‐INH for prophylaxis targeting patients aged 6‐11 years, the interim analysis in six patients showed that both doses reduced the monthly number of attacks by a mean of 1.89 compared with the BOP . In the complete study described here, mean (percentage) reduction in monthly number of attacks relative to the BOP was 2.58 (71.1%) with 500 U C1‐INH and 2.98 (84.5%) with 1000 U C1‐INH.…”

Section: Discussionmentioning

confidence: 62%

“…In Europe and the United States, C1‐INH (Cinryze; Shire) was recently approved for routine prophylaxis in patients aged ≥6 years, but before this study was initiated, it was only approved for adult and adolescent patients. Interim results of this study were previously published . This article describes full study results in 12 patients.…”

Section: Introductionmentioning

confidence: 83%

“…Shire HGT (A Takeda Company) provided funding to Excel Medical Affairs for support in writing and editing this manuscript. Interim data were published in International Archives of Allergy and Immunology . We are saddened by the recent loss of one of the co‐authors of this manuscript, Dr. Dumitru Moldovan.…”

Section: Acknowledgmentsmentioning

confidence: 99%

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A randomized trial of human C1 inhibitor prophylaxis in children with hereditary angioedema

Aygören‐Pürsün

Soteres²,

Nieto-Martinez³

et al. 2019

Pediatric Allergy Immunology

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BackgroundPatients with hereditary angioedema with C1 inhibitor deficiency or dysfunction have burdensome recurrent angioedema attacks. The safety, efficacy, and health‐related quality of life (HRQoL) outcomes of C1 inhibitor (C1‐INH) prophylaxis (intravenously administered) in patients aged 6‐11 years were investigated.MethodsEligible patients were enrolled in a randomized, single‐blind, crossover, phase 3 trial. After a 12‐week baseline observation period (BOP), patients received 500 or 1000 U C1‐INH, twice weekly, for 12 weeks before crossing over to the alternate dose for 12 weeks. The primary efficacy end‐point was the monthly normalized number of angioedema attacks (NNA). HRQoL was assessed using the EuroQoL 5‐dimensional descriptive system youth version and visual analog scale (EQ‐VAS).ResultsTwelve randomized patients had a median (range) age of 10.0 (7‐11) years. Mean (SD) percentage reduction in monthly NNA from BOP was 71.1% (27.1%) with 500 U and 84.5% (20.0%) with 1000 U C1‐INH. Mean (SD) within‐patient difference (−0.4 [0.58]) for monthly NNA with both doses was significant (P = 0.035 [90% CI, −0.706 to −0.102]). Cumulative attack severity, cumulative daily severity, and number of acute attacks treated were reduced. No serious adverse events or discontinuations occurred. Mean EQ‐VAS change from BOP to week 9 of treatment (500 U C1‐INH, 10.4; 1000 U C1‐INH, 21.6) was greater than the minimal important difference, indicating a meaningful HRQoL change.ConclusionsC1‐INH prophylaxis was effective, safe, and well tolerated in children aged 6‐11 years experiencing recurrent angioedema attacks. A post hoc analysis indicated a meaningful improvement in HRQoL with C1‐INH.Trial registrationClinicalTrials.gov identifier NCT02052141.

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“…The study's safety findings are generally consistent with those in the interim analysis and with pediatric and adult subgroups in other C1‐INH studies …”

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 83%

Section: Acknowledgmentsmentioning

confidence: 99%

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A randomized trial of human C1 inhibitor prophylaxis in children with hereditary angioedema

Aygören‐Pürsün

Soteres²,

Nieto-Martinez³

et al. 2019

Pediatric Allergy Immunology

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“…Recently, the efficacy and safety of Cinryze, a nano-filtered human plasma-derived C1-INH, has been proven in children with HAE [80]. …”

Section: The Diagnostic Abc For Aementioning

confidence: 99%

Recent Advances in Clinical Allergy and Immunology

Simon

2018

Int Arch Allergy Immunol

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Allergic diseases are of great concern because of their high prevalence, which is still rising in several regions, their impact on patients’ physical and psychological health, the huge burden they place on patients’ quality of life, as well as the socioeconomic consequences that they cause. Recent research has provided new data on both genetic and environmental risk factors of atopic/allergic diseases. The application of new technologies such as “omics” has allowed a better understanding of the pathogenesis and has helped with the identification of therapeutic targets. Immense progress has been made in developing and applying novel, targeted therapies, for example for asthma and urticaria. Intensive efforts are being made to find biomarkers that help to classify patients, to identify their potential responsiveness to specific therapies, and to monitor the disease severity. Based on recent insights in the pathogenesis of food allergy and drug hypersensitivity, novel strategies for diagnostics, allergen avoidance, and induction of tolerance have been developed. Here, we summarize important findings in the field of clinical allergy and immunology with a special focus on asthma, allergic rhinitis, atopic dermatitis, food allergy, urticaria, angioedema, and drug hypersensitivity.

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Clinical manifestations of hereditary angioedema and a systematic review of treatment options

Rosi‐Schumacher

Shah

Craig

et al. 2021

Laryngoscope Investig Oto

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Objective This study systematically reviews the existing literature on the management of hereditary angioedema (HAE) and provides an update on the clinical presentation and specific therapies. Methods A literature search of PubMed and Embase databases was conducted from start of the database to February 2021. Inclusion criteria included relevant systematic reviews, randomized control clinical trials, prospective and retrospective cohort studies, and outcomes research published in English and available in full‐text. Out of 310 candidate articles, a total of 55 articles were included in our study. Results The most common genetic form of HAE in up to 85% of cases is caused by low levels of C1 esterase inhibitor (C1‐INH) protein, leading to a bradykinin‐mediated increase in vascular permeability. During an attack of HAE, abortive treatment with C1‐INH replacement is most commonly described, however, icatibant, ecallantide, or fresh frozen plasma are also used. Long‐term prophylaxis in the form of C1‐INH replacement (subcutaneous or intravenous), monoclonal antibodies targeting plasma kallikrein, attenuated androgens, and transexemic acid should be considered for those who suffer from frequent, severe attacks. Conclusion Progressively distal involvement of the upper airway, especially the larynx, has been shown to pose an increased risk of asphyxiation and death in the acute presentation of HAE. Evaluation by an otolaryngologist is often sought during the emergent clinical management of HAE; therefore, it is prudent that the consulting physician is well‐versed in the prompt recognition, triage of patients, and appropriate treatment modalities. Level of Evidence 1A.

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

Cited by 22 publications

References 22 publications

A randomized trial of human C1 inhibitor prophylaxis in children with hereditary angioedema

A randomized trial of human C1 inhibitor prophylaxis in children with hereditary angioedema

Recent Advances in Clinical Allergy and Immunology

Clinical manifestations of hereditary angioedema and a systematic review of treatment options

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