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

BACKGROUND: Hereditary angioedema (HAE) is characterized byrecurrent, debilitating attacks of edema of the face, trunk, limbs,abdomen, and genitourinary and respiratory tracts, which generallyrequire immediate treatment with acute medications (on-demandtherapy). In June 2017, the U.S. FDA approved C1 esterase inhibitorsubcutaneous (human; C1-INH [SC], HAEGARDA, CSL Behring) asroutine prophylaxis to prevent attacks in adolescent and adult patientswith HAE, based on the phase 3 COMPACT clinical trial. This studydemonstrated 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-demandtherapy relative to placebo.OBJECTIVE: The purpose of this analysis was to assess the use of ondemandtherapy before and during use of prophylactic treatment withC1-INH (SC) in the COMPACT trial.METHODS: The COMPACT trial included a screening period of up to4 weeks and a run-in period of up to 8 weeks, followed by 2 consecutive16-week treatment periods in which patients self-administeredC1-INH (SC) and placebo in a crossover manner. Use of on-demandtherapy in the pre-randomization period (ie, screening and run-inperiods) 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 43patients randomized to receive C1-INH (SC) 60 IU/kg. During the prerandomizationperiod (up to 12 weeks), 78 uses (58%) of C1-INH (IV)therapy (Berinert, CSL Behring), 56 uses (42%) of icatibant, and 1 useof other C1-INH (IV) therapy were reported. During prophylaxis withC1-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 mediannumber of uses of on-demand medications decreased from 3 during thepre-randomization period to 1 during prophylaxis with C1-INH (SC) 60IU/kg, a median reduction of 75% (95% CI: 50 to 100%, P<0.0001). Inthe pre-randomization period, 5/43 patients (12%) used no on-demandtherapy, whereas during prophylaxis with C1-INH (SC) 60 IU/kg, 21/43patients (49%) used no on-demand therapy.CONCLUSIONS: Patients with HAE used less on-demand therapyduring prophylactic treatment with C1-INH (SC) than during thepre-randomization period (ie, no prophylaxis). The reduction in useof on-demand therapy for HAE attacks will have cost implications.