Recombinant human C1‐inhibitor in the treatment of acute angioedema attacks

Choi, Goda; Soeters, Maarten R.; Farkas, Henriette; Varga, Lilian; Obtułowicz, Krystyna; Bilo, Barbara; Porębski, Grzegorz; Hack, C. E.; Verdonk, René; Nuijens, Jan H.; Levi, Marcel

doi:10.1111/j.1537-2995.2007.01239.x

Cited by 91 publications

(53 citation statements)

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“…Patients could participate when they were older than 12 years, had signed informed consent and had a plasma level of functional C1INH < 50% of normal to confirm the diagnosis [24]. They were instructed to come to a clinical centre when they had onset of moderate to severe angioedema symptoms at any anatomical location.…”

Section: Patientsmentioning

confidence: 99%

“…All patients included in this study were enrolled into two randomized, double-blind, placebo-controlled studies to evaluate recombinant human C1INH (rhC1INH) as a treatment for hereditary angioedema attacks [24][25][26]. Patients could participate when they were older than 12 years, had signed informed consent and had a plasma level of functional C1INH < 50% of normal to confirm the diagnosis [24].…”

Section: Patientsmentioning

confidence: 99%

“…Hence, CRP levels reflect the release of these cytokines in vivo. In the present study we analysed CRP levels in a cohort of HAE patients enrolled in randomized controlled trials with recombinant human C1INH [23][24][25][26]. As part of the clinical protocol, CRP levels were measured at various time-points [26].…”

Section: Introductionmentioning

confidence: 99%

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C-reactive protein levels in hereditary angioedema

Hofman

Relan

Hack

2014

Clinical and Experimental Immunology

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SummaryHereditary angioedema (HAE) patients experience recurrent episodes of angioedema attacks that can be painful, disfiguring and even life-threatening. The disorder results from a mutation in the gene that controls the synthesis of C1-inhibitor (C1INH). C1INH is a major regulator of activation of the contact system. It is often assumed that attacks results from uncontrolled local activation of the contact system with subsequent formation of bradykinin. To evaluate the involvement of inflammatory reactions in HAE, we analysed C-reactive protein (CRP) levels. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. For the current study we analysed CRP levels when patients were asymptomatic, during a clinical attack and in a follow-up period, and correlated these with the clinical manifestations of the attack. Data from 68 HAE patients were analysed and included CRP levels on 273 occasions. While asymptomatic, 20% of the patients analysed had increased CRP. At the onset of the attack (P = 0·049) and during the next 24 h CRP rose significantly (P = 0·002) in patients with an abdominal location, and post-attack levels were significantly higher in these patients than in patients with attacks at other locations (P = 0·034). In conclusion, CRP levels are elevated in a substantial proportion of asymptomatic HAE patients. Levels of CRP increase significantly during an abdominal attack. These data suggest low-grade systemic inflammatory reactions in HAE patients as well as a triggering event for attacks that starts prior to symptom onset.

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Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

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C-reactive protein levels in hereditary angioedema

Hofman

Relan

Hack

2014

Clinical and Experimental Immunology

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“…The human protein is then isolated from the milk. This company is in the late stages of testing their product, called Rhucin, in treatment of HAE attacks[21]. …”

Section: Recombinant C1 Inhibitormentioning

confidence: 99%

“…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. This is presumably because the rabbit glycosylates proteins differently from humans, and the C1 inhibitor is a heavily glycosylated 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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Affinity Chromatography–Fractionated andDNA‐Engineered Plasma Proteins

Radosevich

Burnouf

2009

Encyclopedia of Industrial Biotechnology

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Biopharmaceutical plasma protein products obtained by the industrial fractionation of human plasma or by DNA engineering technologies, most often relying on synthesis in mammalian cell lines, are essential, high‐value added medicines used to treat a variety of congenital or acquired blood coagulation, immunological, or metabolic disorders. The quality of these products is largely dependent upon the characteristics of their extraction procedures which have a direct impact on the protein impurity profile and pathogen safety. Affinity chromatography has developed into a key industrial tool to purify these therapeutic protein products, most particularly those present in trace amounts in plasma. While various immobilized affinity ligands, such as heparin, monoclonal antibodies, and, to a lesser extent, gelatine, have been used for many years to extract or polish coagulation factors, there is now a pronounced interest in the evaluation of specifically designed peptide or mixed‐mode ligands that could improve extraction productivity of a wider range of plasma products, including IgG, alpha 1‐antitrypsin (AAT), and “orphan drug” proteins, like some coagulation factors and anticoagulants. This paper reviews the current status in the use of affinity chromatography procedures in the industrial manufacture of plasma‐derived (PD) and recombinant‐protein therapeutic products.

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Recombinant human C1‐inhibitor in the treatment of acute angioedema attacks

Abstract: The transgenically produced rHuC1INH was successfully used in the treatment of acute angioedema attacks in patients with hereditary C1-inhibitor deficiency.

Cited by 91 publications

References 10 publications

C-reactive protein levels in hereditary angioedema

C-reactive protein levels in hereditary angioedema

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

Affinity Chromatography–Fractionated andDNA‐Engineered Plasma Proteins

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