Long-term outcomes with subcutaneous C1-inhibitor replacement therapy for prevention of hereditary angioedema attacks

Publication date: Available online 15 February 2019

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Timothy Craig, Bruce Zuraw, Hilary Longhurst, Marco Cicardi, Konrad Bork, Clive Grattan, Constance Katelaris, Gordon Sussman, Paul K. Keith, William Yang, Jacques Hébert, Jana Hanzlikova, Petra Staubach-Renz, Inmaculada Martinez-Saguer, Markus Magerl, Emel Aygören-Pürsün, Henriette Farkas, Avner Reshef, Shmuel Kivity, Sergio Neri

Abstract

BACKGROUND

For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA^®, CSL Behring) was established in the 16-week COMPACT trial.

OBJECTIVE

To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC).

METHODS

Open-label, randomised, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naïve or who had completed the COMPACT trial, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional up-titration to optimise prophylaxis. ClinicalTrials.gov registration: NCT02316353.

RESULTS

126 patients with a monthly attack rate of 4.3 in 3 months prior to entry in the COMPACT program were enrolled and treated for a mean of 1·5 years; 44 patients (34·9%) had >2 years exposure. Median steady-state C1-INH functional activity increased to a maximum of 73.0% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11·3 and 8·5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualised attack rates were 1·3 and 1·0, respectively and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for >2 years, 19 (83%) were attack-free during months 25–30 of treatment.

CONCLUSION

In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms.

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