gms | German Medical Science

Objective: The rare autosomal dominant disease HAE manifests as attacks of cutaneous or submucosal oedema. Laryngeal attacks can cause asphyxiation and may require emergency care and intubation. We analysed (posthoc) laryngeal attacks treated with icatibant (Firazyr^®, Shire, Eysins, Switzerland) in the Phase III For Angioedema Subcutaneous Treatment studies: FAST-1, -2 and -3 (NCT00097695, NCT00500656, NCT00912093)(Cicardi. NEJM 2010; Lumry.Ann Allergy Asthma Immunol 2011; Baş.Allergy 2013).

Methods: Studies included controlled and open-label extension (OLE) phases, during which laryngeal attacks could be treated by a healthcare professional with a subcutaneous injection of icatibant 30mg. In FAST-3, patients and investigators recorded time of perceived initial symptom improvement, and patients assessed time of almost complete symptom relief on a 5-symptom visual analogue scale (skin swelling, skin pain, abdominal pain, difficulty swallowing, voice change). In the larger pooled OLE sample, we analysed patient-assessed initial symptom improvement and laryngeal symptom severity over time (assessed by patients on a 5-point scale, absent to very severe).

Results: For 27 first icatibant-treated laryngeal attacks in FAST-3, patient- and investigator-assessed median (95% CI) time to initial symptom improvement was 0.7h (0.4-0.9) and 0.8h (0.5-1.1); median time to almost complete symptom relief was 6.0h (3.0-24.3). Pooled OLE data included 110 laryngeal attacks (severe 31.8%) in 52 patients. Patient-assessed median time to initial symptom improvement was 0.6h (0.5-0.9;66 attacks). Most symptoms were absent/mild 4h post-treatment (difficulty swallowing 82/110 attacks; voice change 89/110 attacks).

Conclusions: Icatibant provided improvements in laryngeal HAE attacks within 1 hour.

Unterstützt durch: Shire

Der Erstautor weist auf folgende Interessenkonflikte hin:

• Jens Greve: Has been an investigator in company-sponsored scientific studies for BioAlliance Pharma, CSL Behring, Jerini and ViroPharma; has acted in a consultant/advisor capacity for Shire and Viropharma; has received travel grants from Shire and Viropharma for presenting at a scientific congress; and has lectured/spoken at a company-sponsored meeting for Shire.
• Murat Baş: Has acted in a consultant/advisor capacity and lectured/spoken at a company-sponsored meeting for Shire; has received a research grant for participating in a company-sponsored scientific study and a travel grant from Shire; has been an investigator in company-sponsored scientific studies for Jerini, Shire, Pharming and ViroPharma, and has received honoraria from HAL Allergy Group and Shire.
• Ulrich Strassen: Has acted in a consultant/advisor capacity for Shire and Viropharma; has been an investigator in company-sponsored scientific studies for Shire, Pharming and ViroPharma; has received a travel grant from Shire.
• Jonathan A. Bernstein: Has been a clinical investigator for CSL Behring, Dyax, Pharming, Shire and ViroPharma; a speaker for CSL Behring, Dyax, Shire and ViroPharma; and a consultant for CSL Behring, Dyax, ViroPharma and Shire.
• William R. Lumry: Has received speaker fees from CSL Behring, Dyax, Shire and ViroPharma; and research grant support from CSL Behring, Dyax, Pharma NV, Shire and ViroPharma. He is also an advisor to BioCryst, CSL Behring, Dyax, Shire and ViroPharma.
• Marc Riedl: Received research funding from CSL Behring, Dyax, Pharming, Shire and ViroPharma, and has served as a Scientific Consultant for BioCryst, CSL Behring, Dyax, Isis, Santaurus, Shire and ViroPharma.
• Jovanna Baptista: is a full-time employee of Shire.
• Thomas Hoffmann: Has acted in a consultant/advisor capacity and lectured/spoken at a company-sponsored meeting for Shire; has received a travel grant from Shire; and has been an investigator in company-sponsored scientific studies for CSL Behring, BioAlliance Pharma, Jerini and ViroPharma.