Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks

Craig, Timothy J.; Levy, Robyn J.; Wasserman, Richard L.; Bewtra, Againdra K.; Hurewitz, David; Obtułowicz, Krystyna; Reshef, Avner; Ritchie, Bruce; Moldovan, Dumitru; Shirov, Todor; Grivcheva‐Panovska, Vesna; Kiessling, Peter; Keinecke, Heinz Otto; Bernstein, Jonathan A.

doi:10.1016/j.jaci.2009.07.017

Cited by 300 publications

(294 citation statements)

References 33 publications

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“…Level I evidence for acute treatment of C1‐INH‐HAE has been reviewed for pdC1‐INH Be , pdC1‐INH Ci , recombinant human C1‐INH (rhC1‐INH) (Rhucin/Ruconest ® ), kallikrein inhibitor ecallantide (Kalbitor ® ), and bradykinin B2 receptor antagonist icatibant (Firazyr ® ) 85, 91, 92, 95, 96, 97, 98, 99. Unfortunately, these treatments have been licensed mainly for adults with pediatric licensing pending and ages for licenses varying by jurisdiction.…”

Section: Resultsmentioning

confidence: 99%

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International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

Farkas

Martinez‐Saguer²,

Bork

et al. 2016

Allergy

174

308

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BackgroundThe consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1‐INH‐HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1‐INH‐HAE.MethodsDuring an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 (www.haenet.hu), pediatric data were presented and discussed and a consensus was developed by voting.ResultsThe symptoms of C1‐INH‐HAE often present in childhood. Differential diagnosis can be difficult as abdominal pain is common in pediatric C1‐INH‐HAE, but also commonly occurs in the general pediatric population. The early onset of symptoms may predict a more severe subsequent course of the disease. Before the age of 1 year, C1‐INH levels may be lower than in adults; therefore, it is advisable to confirm the diagnosis after the age of one year. All neonates/infants with an affected C1‐INH‐HAE family member should be screened for C1‐INH deficiency. Pediatric patients should always carry a C1‐INH‐HAE information card and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma‐derived C1‐INH, recombinant C1‐INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical trials are underway with additional drugs. It is recommended to follow up patients in an HAE comprehensive care center.ConclusionsThe pediatric‐focused international consensus for the diagnosis and management of C1‐INH‐HAE patients was created.

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Section: Resultsmentioning

confidence: 99%

“…PdC1‐INH Ci is approved by the FDA and EMA for prophylaxis for adolescents and adults and is licensed for home/self‐therapy. In Brazil, pdC1‐INH Be is approved for home/self‐therapy and for pediatric and adult use 95, 99, 103, 104, 105, 106, 107.…”

Section: Resultsmentioning

confidence: 99%

International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

Farkas

Martinez‐Saguer²,

Bork

et al. 2016

Allergy

174

308

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“…Similar to all drug therapies, C1-esterase inhibitor products also have safety concerns. In a clinical trial evaluating the use of 1 C1-esterase inhibitor (Berinert, CSL-Behring, King of Prussia, PA) in HAE attacks, the following adverse events were observed: headache, abdominal pain, nausea, muscle spasms, pain, diarrhea, and vomiting[42]. The safety results of a study evaluating the efficacy of nanofiltered human C1-esterase inhibitor (CINRYZE, ViroPharma Inc, Exton, PA) in prophylactic therapy show the most common adverse events to be sinusitis, rash, headache, and upper respiratory infection, irrespective of causality (Table 3)[46].…”

Section: Experience With C1-esterase Inhibitor In the Long-term Prophmentioning

confidence: 99%

“…More recently, manufacturing of another C1-esterase inhibitor formulation has incorporated a nanofiltration step through 2 serial 15-nm filters to reduce transmission of enveloped and nonenveloped viruses and possibly prions[43,101]. It is important to note that, as a result of these purification measures, no cases of virus transmission have been attributed to the purified preparations of C1-esterase inhibitor currently available[42,46,87,95,100,102]. …”

Section: Experience With C1-esterase Inhibitor In the Long-term Prophmentioning

confidence: 99%

Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies

Gower¹,

Busse²,

Aygören‐Pürsün³

et al. 2011

World Allergy Organization Journal

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Hereditary angioedema (HAE) caused by C1-esterase inhibitor deficiency is an autosomal-dominant disease resulting from a mutation in the C1-inhibitor gene. HAE is characterized by recurrent attacks of intense, massive, localized subcutaneous edema involving the extremities, genitalia, face, or trunk, or submucosal edema of upper airway or bowels. These symptoms may be disabling, have a dramatic impact on quality of life, and can be life-threatening when affecting the upper airways. Because the manifestations and severity of HAE are highly variable and unpredictable, patients need individualized care to reduce the burden of HAE on daily life. Although effective therapy for the treatment of HAE attacks has been available in many countries for more than 30 years, until recently, there were no agents approved in the United States to treat HAE acutely. Therefore, prophylactic therapy is an integral part of HAE treatment in the United States and for selected patients worldwide. Routine long-term prophylaxis with either attenuated androgens or C1-esterase inhibitor has been shown to reduce the frequency and severity of HAE attacks. Therapy with attenuated androgens, a mainstay of treatment in the past, has been marked by concern about potential adverse effects. C1-esterase inhibitor works directly on the complement and contact plasma cascades to reduce bradykinin release, which is the primary pathologic mechanism in HAE. Different approaches to long-term prophylactic therapy can be used to successfully manage HAE when tailored to meet the needs of the individual patient.

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“…In the Lev study, the product, now called Cinryze, was used at 1000 units per patient with the possibility of the dose being repeated if the patient did not respond[22]. In the Behring study, the product, now known as Berinert, was used at either 10 or 20 units/kg[23]. In the Pharming study the product was used at 50 or 100 units/kg[21]; a higher dose was used because the recombinant protein has a much shorter half-life in the circulation than the plasma-derived protein.…”

Section: Testing Of the New Preparationsmentioning

confidence: 99%

Recombinant and Plasma-Purified Human C1 Inhibitor for the Treatment of Hereditary Angioedema

Frank¹

2010

World Allergy Organization Journal

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BackgroundAgents for prophylaxis of hereditary angioedema (HAE) have been available in the United States for several decades, but their usefulness is limited by side effects and they cannot be used at all in some patients. No agents have been available in the United States to specifically treat acute attacks. HAE types I and II are associated with low functional levels of C1 inhibitor, and evidence accumulated over decades suggests that intravenous infusion of C1 inhibitor is useful for terminating angioedema attacks and for prophylaxis.Key PointsC1 inhibitor derived from pooled human plasma has been available for decades in Europe, and 2 preparations have been recently introduced into the United States. Both have been efficacious in carefully controlled double-blind studies. One preparation, Cinryze, was approved by the U.S. Food & Drug Administration (FDA) for prophylaxis of HAE attacks in October 2008, and the second, Berinert, was approved by the FDA for treatment of acute attacks in October 2009. A third preparation, the recombinant human C1 inhibitor Rhucin, is completing clinical trials. Although not yet approved by the FDA, preliminary results made available suggest that Rhucin, too, is effective in terminating attacks of HAE.ConclusionsAmericans will now have access to effective acute and prophylactic treatments with C1 inhibitor for hereditary angioedema.

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Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks

Abstract: C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief.

Cited by 300 publications

References 33 publications

International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies

Recombinant and Plasma-Purified Human C1 Inhibitor for the Treatment of Hereditary Angioedema

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