Patterns of on-demand medication use in patients with hereditary angioedema treated long-term with prophylactic subcutaneous C1-inhibitor

Background: Hereditary angioedema (HAE) is characterized by recurrent, debilitating attacks of angioedema that may require immediate (on-demand) treatment. HAE prophylactic therapy may reduce the need for on-demand treatment by decreasing the frequency and severity of attacks, which may in turn impact treatment costs. Subcutaneous C1-inhibitor (C1-INH [SC], HAEGARDA(®), CSL Behring) at the FDA-approved dose of 60 IU/kg is indicated as routine prophylaxis to prevent attacks in patients with HAE. In the pivotal phase III COMPACT trial, the median reduction in attack rate relative to placebo was 95% with twice-weekly C1-INH (SC) 60 IU/kg, and the median reduction in on-demand medication use was >99%. Aims: We examined patterns of on-demand medication use in patients treated with C1-INH (SC) 60 IU/kg in a long-term, open-label extension (OLE) of the COMPACT trial. Methods: The OLE of the COMPACT trial was a multicenter, international, randomized, parallel-arm study that evaluated patients aged ≥6 years with ≥4 attacks over 2 consecutive months before enrollment. The trial included patients from the COMPACT trial and C1-INH (SC)-naïve patients. Patients were randomized to receive C1-INH (SC) 40 IU/kg or 60 IU/kg twice weekly for 52 weeks or up to 140 weeks (US patients only). The time-normalized number of uses of medication for treatment of HAE attacks was an exploratory endpoint. Results: Of the 63 patients in the 60 IU/kg group, 35 had a total of 371 attacks, of which 229 (61.7%) were treated with on-demand medication: 84% (192/229) were treated with 1 medication, 62% with C1-INH (IV), and 38% with icatibant. The majority of treated attacks (113/229) were severe. A total of 28 patients (44.4%) had no attacks, 11 (17.5%) had no treated attacks, and 24 (38.1%) had ≥1 treated attack. Post-hoc analysis of annualized on-demand medication use showed that 39 patients (61.9%) treated with C1-INH (SC) 60 IU/kg did not use any on-demand medication; 66.7% used it less than once per year (mean (SD): 3.8 (9.6) uses/year; median: 0.0 uses/year). Between months 25 and 30, 87% of patients (20/23) did not use any on-demand medication (mean: 0.08/month, or ∼1 use/year). Conclusions: On-demand medication use remained consistently low during prophylactic therapy with C1-INH (SC) in the OLE study, with two-thirds of patients using medication less than once per year. Reduction in on-demand medication use over time should be considered in cost-effectiveness analyses of HAE prophylactic therapies.