Kate Johnson

November 12, 2013

BALTIMORE — When patients with hereditary angioedema receive icatibant (Firazyr, Shire) at the first sign of an attack, the duration of symptoms is significantly less than when the drug is withheld until symptoms reach the moderate level, new research shows.

Although icatibant is beneficial in the controlled clinical trial setting, this study "compares healthcare-provider treatment in the setting of a phase 3 study with more real-world treatment in which patients were mostly self-treating," explained lead investigator Marc Riedl, MD, from the Angioedema Center at UC San Diego.

"The reason for the movement toward self-treatment is that it reduces the time to treatment and, therefore, the symptoms and disability associated with these attacks," he told Medscape Medical News.

Dr. Riedl presented the results here at the American College of Allergy, Asthma & Immunology (ACAAI) 2013 Annual Scientific Meeting.

Icatibant, a selective bradykinin B2-receptor antagonist, is the latest of 3 drugs to receive US Food and Drug Administration approval for hereditary angioedema, and the only drug approved for subcutaneous self-administration. The other 2 require intravenous infusion (Berinert, CSL Behring) or administration in the presence of a healthcare provider (Kalbitor, Dyax).

It's all about self-administration.

"Subcutaneous self-administration is less daunting," acknowledged Dr. Riedl. "You can certainly teach patients to do IV self-infusion with a butterfly needle, but sub-Q is simpler and less scary. We are finding that patients are often more enthusiastic about the sub-Q route."

The study compared data from the phase 3 randomized double-blind placebo-controlled FAST-3 trial of icatibant (Ann Allergy Asthma Immunol. 2011;107:529-537) with the more recent postmarketing data from the Icatibant Outcome Survey (PLoS One. 2013;8:e53773).

When FAST-3 was conducted, self-administration was not common. In that study, investigators randomized adults with moderate to very severe nonlaryngeal type I or II angioedema attacks to receive subcutaneous icatibant 30 mg administered by a healthcare professional within 6 hours of an abdominal or cutaneous attack becoming moderate and within 12 hours of attack onset.

In contrast, investigators conducted the survey after self-administration of icatibant was approved for use, and adult patients with mild to very severe nonlaryngeal type I or II hereditary angioedema attacks could either self-administer icatibant after training by a healthcare provider or be treated by a professional.

FAST-3 analyzed 43 patients with 43 attacks, and the survey analyzed 104 patients with 378 attacks. In the survey, 80.2% of the nonlaryngeal attacks were self-treated.

Overall, attacks treated with either self- or provider administration were controlled more quickly than attacks treated in FAST-3.

Table. Outcomes With Icatibant Administration

Median Time Survey Self- and Provider Administration, Hours Survey Provider Administration, Hours FAST-3 Provider Administration, Hours P Value
Attack onset to treatment 1.6 2.0 6.5 <.001
Treatment to symptom resolution 4.1 3.5 8.0 <.0001
Attack duration 7.4 7.3 16.9 <.0001


Although design and specific end points were different in the 2 studies, the analysis shows that early treatment with icatibant, and self-administration in particular, can significantly reduce the morbidity of hereditary angioedema attacks, said Dr. Riedl.

"It's all about self-administration," said Richard Gower, MD, past president of the ACAAI and a hereditary angioedema specialist in private practice in Spokane, Washington.

"The point is that if there is self-administration, or administration at home, it tends to be a lot earlier, the duration of the attack is shorter and less severe, quality of life is increased, convenience is better, and independence is increased. We knew these things, but this nice little study documents this. The guidelines, the practice parameters, and all the other international consensus papers have come out suggesting that there should be self-administration," Dr. Gower noted.

FAST-3 and the Icatibant Outcome Survey were funded by Shire. Dr. Riedl reports financial relationships with Shire, BioCryst, CSL Behring, Dyax, Isis, Pharming, Santaurus, and ViroPharma. Dr. Gower reports financial relationships with Shire, Bausch & Lomb, Boehringer Ingelheim, CSL Behring, Circassia, Dyax, Eli Lilly, Genentech, GlaxoSmithKline, Green Cross, Hollister-Stier, Kedrion, Merck, Mylan, Novartis, Pharming, Roche, Sanofi, Teva, and ViroPharma.

American College of Allergy, Asthma & Immunology (ACAAI) 2013 Annual Scientific Meeting: Abstract P85. Presented November 9, 2013.


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