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

Abstract

BACKGROUND: Hereditary angioedema (HAE) is characterized by recurrent, debilitating attacks of angioedema that may require immediate (on‐demand) treatment with acute medications. HAE prophylactic therapy has the potential to 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] 60 IU/kg, HAEGARDA, CSL Behring) is indicated as routine prophylaxis to prevent attacks in adolescent and adult 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 median reduction in on‐demand medication use was > 99%. OBJECTIVE: To examine patterns of on‐demand medication use among 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. All patients were randomly assigned to receive C1‐INH (SC) 40 IU/kg or 60 IU/kg twice weekly for 52 weeks or up to 140 weeks (for U.S. patients only). The time‐normalized number of uses of medication for the treatment of HAE attacks was an exploratory endpoint. RESULTS: Of the 63 subjects 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% of attacks (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 subjects (44.4%) had no attacks, 11 (17.5%) had no treated attacks, and 24 (38.1%) had at least 1 treated attack. Post‐hoc analysis of annualized on‐demand medication use showed that 39 subjects (61.9%) treated with C1‐INH (SC) 60 IU/kg used no on‐demand medication; 66.7% used it less than once per year (mean [SD]: 3.8 [9.6] uses/yr; median: 0.0 uses/ yr). Between months 25 and 30, 87% of patients (20/23) used no ondemand medication (mean: 0.08/month, or 1 use/yr). CONCLUSIONS: The use of on‐demand medication 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. The reduction in on‐demand medication use over time should be considered in cost‐effectiveness analyses of HAE prophylactic therapies.