Treatment of hereditary angioedema with plasma-derived C1 inhibitor

Prematta, Michael J.; Prematta, Tracy; Craig, Timothy J.

doi:10.2147/tcrm.s3172

Cited by 19 publications

(5 citation statements)

References 26 publications

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“…According to G OMPELS et al , prophylactic use of this drug is recommended within 24 hours before the contemplated intervention [ 29 ]. As confirmed by several publications, pdC1-INH concentrate is highly effective for short-term prophylaxis against procedure-related UAE [ 26 - 29 , 40 ].…”

Section: Introductionmentioning

confidence: 77%

“…Intravenous administration of this agent in a 500 to 1000 U dose is followed by substantial improvement of clinical symptoms within 30 to 60 minutes. In the vast majority of cases, treatment with pdC1-INH usually eliminates symptoms completely within 12 hours [ 9 , 12 , 15 , 26 - 29 ]. Double blind, placebo-controlled studies conducted recently with pdC1-INH concentrate established its recommended dose at 20 U/kg.…”

Section: Introductionmentioning

confidence: 99%

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Management of upper airway edema caused by hereditary angioedema

Farkas

2010

All Asth Clin Immun

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Hereditary angioedema is a rare disorder with a genetic background involving mutations in the genes encoding C1-INH and of factor XII. Its etiology is unknown in a proportion of cases. Recurrent edema formation may involve the subcutis and the submucosa - the latter can produce obstruction in the upper airways and thereby lead to life-threatening asphyxia. This is the reason for the high, 30-to 50-per-cent mortality of undiagnosed or improperly managed cases. Airway obstruction can be prevented through early diagnosis, meaningful patient information, timely recognition of initial symptoms, state-of-the-art emergency therapy, and close monitoring of the patient. Prophylaxis can substantially mitigate the risk of upper airway edema and also improve the patients' quality of life. Notwithstanding the foregoing, any form of upper airway edema should be regarded as a potentially life-threatening condition. None of the currently available prophylactic modalities is capable of preventing UAE with absolute certainty.

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Section: Introductionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Management of upper airway edema caused by hereditary angioedema

Farkas

2010

All Asth Clin Immun

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“…The survey format is also prone to recall bias, which can lead to under- or overestimations of outcomes. An additional limitation is the lack of details captured regarding treatment side effects—severity or specific side effects were not evaluated—but based on the literature, side effects can be assumed to have been generally mild [ 16 ]. Similarly, the degree to which HAE negatively impacted QoL could not be specified, as participants experiencing minor or major impacts on different aspects of their QoL would respond in the same manner by selecting an affirmative response.…”

Section: Discussionmentioning

confidence: 99%

The Disease Burden of Hereditary Angioedema: Insights from a Survey in French-Canadians from Quebec

Boursiquot,

Chapdelaine,

St-Pierre

et al. 2024

Journal of Immunology Research

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Background. Limited data are available on the clinical profile and disease burden of hereditary angioedema (HAE) in Canadians. Objective. This study aimed to assess HAE disease characteristics and the burden of disease in Canadians with HAE types I, II, and normal levels of C1 inhibitor (nC1-INH). Materials and Methods. A 46-item patient survey evaluating clinical characteristics and burden of disease was developed and disseminated by the HAE patient organization Angio-oédeme héréditaire du Québec in Quebec, Canada, from May 2019 to February 2020. The survey received Research Review Board ethics approval. Results. In the 35 respondents, HAE type I was the most common (46%), followed by nC1-INH (43%). Female participants were significantly younger at first symptom presentation than males (p=0.04). Prior to diagnosis, 69% of participants underwent unnecessary treatments and procedures, with a 10-year delay between first symptoms and diagnosis. Before starting the current treatment, 42% of participants experienced weekly HAE attacks. Most participants identified experiencing attacks in the abdomen (89%), followed by the larynx (66%), feet (66%), hands (63%), and face (63%). Most attacks were severe or moderate, yet almost half of patients waited >1 hr before getting medical attention at their last emergency department (ED) visit. HAE was associated with decreased health-related quality of life, leading to significant functional impairment in personal and professional life. As compared to HAE type I/II, patients with HAE nC1-INH were treated more often with tranexamic acid for long-term prophylaxis, and their condition was less controlled, resulting in more attacks and ED visits. Conclusion. HAE manifests in this patient population as frequent moderate-to-severe attacks and a high disease burden; the HAE subtype may differentially affect care requirements. There is an urgent need for increased awareness and education on HAE among treating physicians.

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“…Evaluation of C1-inh in NMO is motivated by its complement inhibition action on the serine protease activities of C1r and C1s in the classical complement pathway [25] , [28] , [29] ; however, C1-inh inhibition of the complement lectin pathway has also been reported [41] and the serine protease inhibition action of C1-inh affects multiple other biological activities, including the coagulation system, the fibrinolytic system, T-lymphocyte activation and the kallikrein contact activation system [25] , [26] . The therapeutic efficacy of C1-inh in HAE involves its action on the kallikrein system [42] , [43] .…”

Section: Discussionmentioning

confidence: 99%

Potential Therapeutic Benefit of C1-Esterase Inhibitor in Neuromyelitis Optica Evaluated In Vitro and in an Experimental Rat Model

2014

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Neuromyelitis optica (NMO) is an autoimmune demyelinating disease of the central nervous system in which binding of anti-aquaporin-4 (AQP4) autoantibodies (NMO-IgG) to astrocytes causes complement-dependent cytotoxicity (CDC) and inflammation resulting in oligodendrocyte and neuronal injury. There is compelling evidence for a central role of complement in NMO pathogenesis. Here, we evaluated the potential of C1-esterase inhibitor (C1-inh) for complement-targeted therapy of NMO. C1-inh is an anti-inflammatory plasma protein with serine protease inhibition activity that has a broad range of biological activities on the contact (kallikrein), coagulation, fibrinolytic and complement systems. C1-inh is approved for therapy of hereditary angioedema (HAE) and has been studied in a small safety trial in acute NMO relapses (NCT 01759602). In vitro assays of NMO-IgG-dependent CDC showed C1-inh inhibition of human and rat complement, but with predicted minimal complement inhibition activity at a dose of 2000 units in humans. Inhibition of complement by C1-inh was potentiated by ∼10-fold by polysulfated macromolecules including heparin and dextran sulfate. In rats, intravenous C1-inh at a dose 30-fold greater than that approved to treat HAE inhibited serum complement activity by <5%, even when supplemented with heparin. Also, high-dose C1-inh did not reduce pathology in a rat model of NMO produced by intracerebral injection of NMO-IgG. Therefore, although C1r and C1s are targets of C1-inh, our in vitro data with human serum and in vivo data in rats suggest that the complement inhibition activity of C1-inh in serum is too low to confer clinical benefit in NMO.

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Treatment of hereditary angioedema with plasma-derived C1 inhibitor

Cited by 19 publications

References 26 publications

Management of upper airway edema caused by hereditary angioedema

Management of upper airway edema caused by hereditary angioedema

The Disease Burden of Hereditary Angioedema: Insights from a Survey in French-Canadians from Quebec

Potential Therapeutic Benefit of C1-Esterase Inhibitor in Neuromyelitis Optica Evaluated In Vitro and in an Experimental Rat Model

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