Subcutaneous C1-inhibitor prophylactic treatment for hereditary angioedema: a budget impact model

Abstract

BACKGROUND: Hereditary angioedema (HAE) is characterized by recurrent, debilitating attacks of edema of the face, trunk, limbs, abdomen, and genitourinary and respiratory tracts, which generally require immediate treatment with acute medications (on-demand therapy). In June 2017, the U.S. FDA approved C1 esterase inhibitor subcutaneous (human; C1-INH [SC], HAEGARDA, CSL Behring) as routine prophylaxis to prevent attacks in adolescent and adult patients with HAE, based on the phase 3 COMPACT clinical trial. This study demonstrated a 95% reduction in the median attack rate with C1-INH (SC) 60 IU/kg and a >99% median reduction in the use of on-demand therapy relative to placebo. OBJECTIVE: The purpose of this analysis was to assess the use of ondemand therapy before and during use of prophylactic treatment with C1-INH (SC) in the COMPACT trial. METHODS: The COMPACT trial included a screening period of up to 4 weeks and a run-in period of up to 8 weeks, followed by 2 consecutive 16-week treatment periods in which patients self-administered C1-INH (SC) and placebo in a crossover manner. Use of on-demand therapy in the pre-randomization period (ie, screening and run-in periods) was compared with use during prophylaxis with C1-INH (SC) 60 IU/kg in the COMPACT study. RESULTS: Data on use of on-demand therapy was available for 43 patients randomized to receive C1-INH (SC) 60 IU/kg. During the prerandomization period (up to 12 weeks), 78 uses (58%) of C1-INH (IV) therapy (Berinert, CSL Behring), 56 uses (42%) of icatibant, and 1 use of other C1-INH (IV) therapy were reported. During prophylaxis with C1-INH (SC) 60 IU/kg (up to 16 weeks), 47 uses of C1-INH (IV, Berinert) therapy (84%) and 9 uses of icatibant (16%) were reported. The median number of uses of on-demand medications decreased from 3 during the pre-randomization period to 1 during prophylaxis with C1-INH (SC) 60 IU/kg, a median reduction of 75% (95% CI: 50 to 100%, P<0.0001). In the pre-randomization period, 5/43 patients (12%) used no on-demand therapy, whereas during prophylaxis with C1-INH (SC) 60 IU/kg, 21/43 patients (49%) used no on-demand therapy. CONCLUSIONS: Patients with HAE used less on-demand therapy during prophylactic treatment with C1-INH (SC) than during the pre-randomization period (ie, no prophylaxis). The reduction in use of on-demand therapy for HAE attacks will have cost implications.