C1 Esterase Inhibitor Prophylaxis Sharply Cuts HAE Attacks

Becky McCall

December 07, 2010

December 7, 2010 (Dubai, United Arab Emirates) — Routine prophylaxis of hereditary angioedema (HAE) with a nanofiltered C1 esterase inhibitor (nf-C1 INH; Cinryze, ViroPharma Inc.) reduced the median attack rate from 3.0 to 0.2 attacks per month in a 1-year study — the largest of its kind to date.

"The attack rate of patients using nf-C1 INH prophylactically was significantly reduced and [the agent was] generally well tolerated," said Paula Busse, MD, from Mount Sinai School of Medicine in New York City, and coauthor of the poster, which was presented here at the World Allergy Organization 2010 International Scientific Conference.

HAE is a disease driven by a deficiency in C1 INH in type 1 disease or a dysfunction of the C1 INH in type 2 disease, Dr. Busse said. It is a genetic disease characterized by recurrent, painful, and potentially life-threatening swelling episodes, often in the face, trunk, and airways, she noted.

Dr. Busse and coinvestigators published a preliminary study in the New England Journal of Medicine earlier this year, which looked at nf-C1 INH as a treatment for acute attacks and as HAE prophylaxis in 22 patients. In the open-label study presented here (LEVP2006-4), 146 participants with HAE experiencing at least 1 attack per month or having a history of laryngeal edema were enrolled at 47 study sites. Participants had been diagnosed with HAE for a median of 17.5 years and were given nf-C1 INH prophylaxis.

"This is the largest double-blinded study ever published on the use of nf-C1 INH for prophylactic treatment of HAE," Dr. Busse told Medscape Medical News.

The study drug was given as prophylaxis at an intravenous dose of 1000 U every 3 to 7 days. it was also given to alleviate acute attacks, which participants recorded as they occurred. Exposure to nf-C1 INH varied from 8 to 959 days; 73% received nf-C1 INH over a period of at least 6 months.

Administration of nf-C1 INH reduced the median monthly HAE attack rate to 0.2 per month (range, 0.0 to 4.6 attacks per month) from a baseline rate of 3 attacks per month (range, 0.08 to 28.00 attacks per month). In addition, 35% of participants reported no attacks during the study, and 86% experienced an average of 1 attack or less per month. HAE attacks were reported by 11.6% of patients.

Commenting on nf-C1 INH during a presentation on HAE, Konrad Bork, MD, from the University Hospital in Mainz, Germany, said it was an exciting new treatment. "Patients received nf-C1 inhibitor concentrate for 12 weeks, compared with placebo, and we saw a large reduction of attack frequency after 3 months of [treatment]. Without a doubt, it is an effective treatment," he asserted.

Dr. Bork said that there was a need for new prophylactic agents above and beyond androgens, which have been used for 30 years. "Androgens are highly effective and cheap, but have many side effects, such as weight gain, menstrual irregularities, liver adenomas, and some carcinomas."

Dr. Busse pointed out that prophylactic treatment is important for patients with frequent symptoms of HAE and that this drug is an advance over the androgens.

"Prophylactic treatment will greatly improve quality of life for these patients. Androgens are frequently difficult for patients to take because of their side effects, and they can not be used in acute treatment," Dr. Busse said.

With more than 65,000 infusions administered to date, the drug is well tolerated. In the Mount Sinai study, the most commonly reported adverse events were headache (5.5%), nausea (4.1%), rash (2.7%), erythema (2.1%), and diarrhea (2.1%). Five subjects experienced thrombotic serious adverse events: myocardial infarction, deep vein thrombosis, pulmonary embolism, and 2 cerebrovascular accidents. There were no hypersensitivity reactions related to nf-C1 INH, with the exception perhaps of 2 events of unknown relation.

A poster presented earlier this year at the American Academy of Allergy, Asthma, and Immunology conference investigated whether self-administration in the home is a feasible solution for the prophylaxis of HAE. They found that 20% of patients self-administered. Nearly 25% of people 30 to 44 years of age reported the highest levels of self-administration. Other patients received nf-C1 INH at physicians' offices or using a home nursing organization.

Dr. Busse has disclosed no relevant financial relationships. Dr. Bork reports conflicts of interest with CSL Behring, Shire, and ViroPharma.

World Allergy Organization (WAO) 2010 International Scientific Conference: Poster 2309. Presented December 7, 2010.

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