D. Levy, J. Chiao, J. Dang, C. Hood, D. Supina, H. Feuersenger
{"title":"预防性皮下C1抑制剂长期治疗遗传性血管性水肿患者的按需用药模式","authors":"D. Levy, J. Chiao, J. Dang, C. Hood, D. Supina, H. Feuersenger","doi":"10.1080/21556660.2019.1658323","DOIUrl":null,"url":null,"abstract":"Abstract 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.","PeriodicalId":15631,"journal":{"name":"Journal of Drug Assessment","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2019-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21556660.2019.1658323","citationCount":"0","resultStr":"{\"title\":\"Patterns of on-demand medication use in patients with hereditary angioedema treated long-term with prophylactic subcutaneous C1-inhibitor\",\"authors\":\"D. Levy, J. Chiao, J. Dang, C. Hood, D. Supina, H. Feuersenger\",\"doi\":\"10.1080/21556660.2019.1658323\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Abstract 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.\",\"PeriodicalId\":15631,\"journal\":{\"name\":\"Journal of Drug Assessment\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2019-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/21556660.2019.1658323\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Drug Assessment\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/21556660.2019.1658323\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Assessment","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/21556660.2019.1658323","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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. 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.