Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial

Riedl, Marc A.; Grivcheva‐Panovska, Vesna; Moldovan, Dumitru; Baker, James; Yang, William H.; Giannetti, Bruno; Reshef, Avner; Andrejević, Sladjana; Lockey, Richard F.; Hakl, Roman; Kivity, Shmuel; Harper, Joseph R.; Relan, Anurag; Cicardi, Marco

doi:10.1016/s0140-6736(17)31963-3

Cited by 58 publications

(46 citation statements)

References 29 publications

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“…Appropriate vaccination for hepatitis A and B should be generally considered for patients in regular/repeated administration of human plasma‐derived products . Routine prophylaxis with pdC1‐INH has been shown to be safe and effective, and it improves quality of life in patients with relatively frequent HAE attacks compared with acute treatment of individual HAE attacks …”

Section: Therapymentioning

confidence: 99%

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2017 revision and update

Maurer

Magerl

Ansotegui

et al. 2018

Allergy

470

974

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Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up‐to‐date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1‐inhibitor (type 1) and HAE with dysfunctional C1‐inhibitor (type 2). The key clinical questions covered by these recommendations are: (1) How should HAE‐1/2 be defined and classified?, (2) How should HAE‐1/2 be diagnosed?, (3) Should HAE‐1/2 patients receive prophylactic and/or on‐demand treatment and what treatment options should be used?, (4) Should HAE‐1/2 management be different for special HAE‐1/2 patient groups such as pregnant/lactating women or children?, and (5) Should HAE‐1/2 management incorporate self‐administration of therapies and patient support measures?

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Section: Therapymentioning

confidence: 99%

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2017 revision and update

Maurer

Magerl

Ansotegui

et al. 2018

Allergy

470

974

View full text Add to dashboard Cite

show abstract

“…The major difference between this agent and the plasma‐derived product is the much shorter half‐life of about 2 hours (probably due to differences in glycosylation) . Nevertheless, recombinant C1 inhibitor was effective in both treating acute angioedema attacks and (more surprisingly) in a prophylactic setting to a similar extent as the plasma‐derived agent …”

Section: Treatment Of C1 Inhibitor Deficiency and Consequences For Hementioning

confidence: 99%

“…48 Nevertheless, recombinant C1 inhibitor was effective in both treating acute angioedema attacks and (more surprisingly) in a prophylactic setting to a similar extent as the plasma-derived agent. 49,50 In view of the central role of C1 inhibitor on the contact activation system and endogenous fibrinolytic system restoration of C1 inhibi- Based on these results, lanadelumab is now (pre-) approved in the US, EU, Canada, Australia, and Switzerland for prevention of HAE attacks in patients aged ≥12 years. In addition, BCX7353, an oral small-molecule inhibitor of plasma kallikrein was evaluated in a phase II dose-escalation trial in 77 patients.…”

Section: Treatment Of C1 Inhibitor Deficiency and Consequences For mentioning

confidence: 99%

Hereditary angioedema: Linking complement regulation to the coagulation system

Levi

Cohn

2019

Research and Practice in Thrombosis and Haemostasis

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Congenital deficiency of C1 inhibitor, the main inhibitor of the classic complement system pathway, leads to paroxysmal angioedema (hereditary angioedema) that can be debilitating or life‐threatening for affected patients. In the past few years many new insights on the pathogenesis of angioedema formation in the presence of low levels of C1 inhibitor has been accumulated. There is a central role for bradykinin that is released upon activation of the kallikrein‐kinin system that is insufficiently controlled by adequate levels of C1 inhibitor. As C1 inhibitor also possesses a central regulatory role of other plasma systems, including the contact activation system of coagulation and the plasminogen‐plasmin system that governs endogenous fibrinolysis, it is interesting to observe the effects of C1 inhibitor deficiency on activation of these systems and relevance for hemostasis in vivo and thrombo‐embolic disease. Interestingly, and despite significant activation of these pathways, C1 inhibitor deficiency is not at all associated with a hemorrhagic tendency or prothrombotic state. New therapeutic options for treatment of C1 inhibitor efficiency have become available in recent years, including various forms of C1 inhibitor concentrate. Restoration of C1 inhibitor levels in patients with hereditary angioedema has not resulted in thrombotic complications or any other relevant disorder associated with the hemostatic system.

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“…LTP is indicated in patients not sufficiently controlled with on-demand therapy. Attenuated androgens, antifibrinolytics, and C1INH concentrates have all proved their efficacy in LTP in controlled clinical trials against placebos in patients with HAE and C1INH deficiency [56, 115]. …”

Section: Therapiesmentioning

confidence: 99%

Hereditary Angio-Oedema for Dermatologists

Bygum¹

2019

Dermatology

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Among angio-oedema patients, hereditary angio-oedema (HAE) should not be overlooked. Besides skin swellings, these patients might have very painful abdominal attacks and potentially life-threatening angio-oedema of the upper airway. They will not respond to traditional anti-allergic therapy with antihistamines, corticosteroids, and adrenaline, and instead need specific drugs targeting the kallikrein-kinin pathway. Classically, patients with HAE have a quantitative or qualitative deficiency of the C1 inhibitor (C1INH) due to different mutations in SERPING1, although a new subtype with normal C1INH has been recognised more recently. This latter variant is diagnosed based on clinical features, family history, or molecular genetic testing for mutations in F12, ANGPT1,or PLG.The diagnosis of HAE is often delayed due to a general unfamiliarity with this orphan disease. However, undiagnosed patients are at an increased risk of unnecessary surgical interventions or life-threatening laryngeal swellings. Within the last decade, new and effective therapies have been developed and launched for acute and prophylactic therapy. Even more drugs are under evaluation in clinical trials. It is therefore of utmost importance that patients with HAE are diagnosed as soon as possible and offered relevant therapy with orphan drugs to reduce morbidity, prevent mortality, and improve quality of life.

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Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial

Cited by 58 publications

References 29 publications

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2017 revision and update

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2017 revision and update

Hereditary angioedema: Linking complement regulation to the coagulation system

Hereditary Angio-Oedema for Dermatologists

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