METHODS: In the COMPACT study, patients self-administered C1-INH (SC) or placebo twice weekly in a double-blind, crossover manner over two 16-week treatment periods. Per study design, the first 2 weeks of each treatment period were excluded in the primary analysis (time-normalized number of HAE attacks) to account for possible wash-in/wash-out effects, a methodological aspect of any crossover trial. In the present post-hoc analysis, we evaluated results from the first 2 weeks of treatment to determine how early the preventive effect of C1-INH (SC) can be observed.
RESULTS: In the first 2 weeks of treatment, 10/45 patients (22%) experienced attacks with 60 IU/kg versus 34/45 patients (76%) with placebo. A total of 14 attacks occurred (none severe) during the first 2 weeks with 60 IU/kg treatment versus 70 attacks with placebo (17 severe). Population pharmacokinetic models indicate that C1-INH functional activity exceeds the critical threshold of 40% after the second dose (Cmax=60.7%, Tmax=58.7 h, Ctrough=48%).
CONCLUSIONS: The preventive effect of C1-INH (SC) is already evident in the first 2 weeks of switching from on-demand treatment, as evidenced by less severe and fewer attacks during prophylaxis.