Cinryze Infusion Reverses Plasma Activation In Hereditary Angioedema

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Main Category: Immune System / Vaccines
Also Included In: Allergy;  Clinical Trials / Drug Trials
Article Date: 17 Mar 2009 - 4:00 PDT

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WASHINGTON DC - New data show that replacement therapy with Cinryze (C1 inhibitor-nf) infusion reverses all abnormalities of the plasma bradykinin-forming pathway and fibrinolysis that are responsible for the swelling attacks in patients with hereditary angioedema (HAE).

Allan Kaplan, MD, Professor of Medicine at the Medical University of South Carolina in Charleston, and colleagues assessed the reversal of abnormalities of the bradykinin-forming pathway and fibrinolysis in HAE patients after swelling episodes had been treated with intravenous C1INH.

The new findings were released at the 2009 Annual American Academy of Allergy, Asthma and Immunology (AAAAI).

Prior research by these investigators had demonstrated increased baseline levels of bradykinin, C4a, and plasma-alpha2 antiplasmin complexes in HAE plasma compared to normal plasma, and production of Hageman factor fragment upon in vitro activation of HAE plasma.

In the present analysis, Dr. Kaplan's group obtained samples of plasma from nine HAE patients at a quiescent period, during a swelling episode, and at one hour, four hours, and 12 hours after the completion of a C1INH infusion.

The investigators found that while activated factor XII, kallikrein and plasmin were 'strikingly" elevated at baseline compared to control plasma, there was a progressive decline of activity to normal for factor XII and plasmin.

Kallikrein levels decreased in seven patents after one hour and decreased in all patients thereafter.

Bradykinin levels, which were initially increased in all patients, increased dramatically during a swelling attack, decreased to baseline at one hour, and then decreased at four and 12 hours after infusion.

"These findings underscore the importance of C1 inhibition in the pathway physiology of HAE attacks," said Dr. Kaplan. "This greater understanding of the mechanism of action of Cinryze helps to explain the positive safety and efficacy profile observed in patients treated for routine prophylaxis or acute attack of HAE."

Hereditary angioedema is a rare genetic disorder that is typically due to a deficiency of C1 inhibitor with gene defects that reduce plasma levels or production of a dysfunctional protein. The condition is characterized by recurrent, unpredictable, debilitating, and potentially life- threatening attacks of inflammation affecting the larynx, abdomen, face, extremities and urogenital tract, leading to in some cases as many as 100 days of incapacitation per year.

By Jill Stein
Jill Stein is a Paris-based freelance medical writer.
jillstein03@gmail.com


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