Fran Lowry

November 09, 2011

November 9, 2011 (Boston, Massachusetts) — Patients with acute hereditary angioedema had durable responses to treatment with ecallantide. Only a small percentage of patients had a relapse and only 1 patient experienced attack rebound, researchers reported here at the American College of Allergy, Asthma & Immunology 2011 Annual Scientific Meeting.

Ecallantide is a potent selective inhibitor of plasma kallikrein, and has a half-life of approximately 2 hours, explained lead author, Jonathan A. Bernstein, MD, from the University of Cincinnati College of Medicine, Ohio.

"This agent is used as on-demand therapy. It has a short half-life but, despite that, it seems to have a durable response in the majority of patients treated with hereditary angioedema attacks," Dr. Bernstein told Medscape Medical News.

Dr. Jonathan Bernstein

Dr. Bernstein and his team assessed the durability of efficacy in the 24-hour period after treatment with ecallantide, and the potential for rebound and relapse, in a combined analysis of 2 double-blind placebo-controlled studies: EDEMA 3 and EDEMA 4.

Patients with moderate to severe hereditary angioedema attacks affecting any anatomic location were randomized to 30 mg of subcutaneous ecallantide (n = 70) or to placebo (n = 71).

The efficacy measures, which were assessed at 4 and 24 hours after dosing, included the mean symptom complex severity score, the treatment outcome score, and global response (a 5-point measure reflecting overall improvement or worsening from baseline).

Rebound was defined as a worsening of the attack beyond baseline at 24 hours. It was considered likely if symptoms worsened on all 3 measures, possible if symptoms worsened on 2 of the measures, and unlikely if symptoms worsened on just 1 measure.

Relapse was defined as a worsening of the attack at 24 hours, but not beyond baseline. Likely, possible, and unlikely relapses were judged using to the same criteria as for rebound.

Four hours after treatment, improvement was greater in the ecallantide group than in the placebo group, with 42 patients (60%) in the ecallantide group showing improvement on all 3 measures, compared with 26 (37%) in the placebo group.

No patients met the criteria for likely rebound, 1 patient in the ecallantide group and 2 in the placebo group met the criteria for possible rebound, and 1 patient in the ecallantide group met the criteria for unlikely rebound.

The 1 possible rebound in the ecallantide group was in a 17-year-old male with a body mass index of 40 kg/m². He had moderate abdominal symptoms at baseline; his symptoms improved at 4 hours, but his conditioned worsened.

Further investigation of this patient showed that he had been treated with ecallantide for 29 other attacks, including a laryngeal attack. "I think in this type of case, patients with this profile should be monitored to assess the potential benefit of administering a dose B," Dr. Bernstein said.

There were 2 likely and 2 possible cases of relapse in the ecallantide group and in the placebo group, and 3 unlikely cases of relapse in the ecallantide group and 1 in the placebo group.

Among the potential rebound or relapse patients, 5 of 9 patients in the ecallantide group and 3 of 7 in the placebo group had symptoms at multiple sites. Most of these symptoms were moderate, and none of the patients in either group had symptoms emerge after dosing, Dr. Bernstein said.

One likely relapse patient in the ecallantide group who had abdominal symptoms required medical intervention, as did 1 likely relapse patient in the placebo group who had peripheral symptoms.

"In cases where there is evidence of likely or possible rebound relapses, there should be a second dose that they can be prepared and get therapeutic benefits," Dr. Bernstein said. "They should have a second dose available at home. They should have a plan that even if they improve — and as we saw, there was a durable response after 4 hours in the majority of cases — they should still have access to that second dose up to 24 hours later."

Commenting on this study for Medscape Medical News, Todd A. Mahr, MD, from the Gundersen Lutheran Medical Center in La Cross, Wisconsin, who comoderated the oral session, said: "It helps us — in this population of patients with hereditary angioedema — when we use this product to know what the risk of relapse will be. This study helps to reassure us that this risk is low, not zero, but low."

Dr. Bernstein reports financial relationships with Dynova, Flint Hills, Dyax, ViroPharma, Shire, CSL-Behring, Teva, AstraZeneca, and Pharming. Dr. Mahr reports financial relationships with ISTA, Merck, Novartis, Alcon, AstraZeneca, GlaxoSmithKline, and Genentech.

American College of Allergy, Asthma & Immunology (ACAAI) 2011 Annual Scientific Meeting: Abstract 8. Presented November 6, 2011.


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