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Background: To estimate health-related quality-of-life changes in patients with hereditary angioedema due to C1-inhibitor(C1-INH) deficiency who received subcutaneous C1-INH with recombinant hyaluronidase (rHuPH20) for attack prophylaxisin a randomized, double-blind, dose-ranging, cross-over study.

Methods: Patientswith type I/II hereditary angioedema received 1000 U of C1-INH with 24,000 U of rHuPH20 or 2000 U ofC1-INH with 48,000 U of rHuPH20 every 3–4 days for 8 weeks and then crossed over for another 8-week period. The study wasterminated early as a precaution related to non-neutralizing antibodies to rHuPH20. The Angioedema Quality of Life questionnaire(AE-QoL) was administered at weeks 1 and 5 of both periods, and at 1 week after the second treatment period. Changes in AE-QoLscores were calculated over both treatment periods and within each treatment period for patients with4 weeks of treatment.

Results: Forty-one patients had evaluable AE-QoL data, and 22 patients completed treatment. At screening, 43% of thepatients were receiving intravenous C1-INH. A significant average AE-QoL total score decline (improvement) of8.1 (95%confidence interval,13.7 to2.5) was observed from baseline to the end of the study, and significant AE-QoL score declineswere observed in the Functioning, Fear/Shame, and Nutrition domains. Patients on 2000 U reported higher mean AE-QoLscore declines in Functioning and Nutrition domains relative to the 1000 U dose. Overall, 43.9% of all the patients, 45.5% ofthe study completers, and 46.7% of the nonprophylaxis users at baseline on high treatment doses achieved a reduction in theAE-QoL total score of six points.

Conclusion: Despite early termination and prestudy prophylactic intravenous C1-INH use by 43% of the patients,improved AE-QoL scores were observed after16 weeks of subcutaneous C1-INH–rHuPH20 prophylaxis.