Efficacy and Safety of an Intravenous C1-Inhibitor Concentrate for Long-Term Prophylaxis in Hereditary angioedema

Abstract

Background:The plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH) is approved in the United States as an intravenous (IV) on-demand treatment for hereditary angioedema (HAE) attacks, and, in Europe, as on demand and short-term prophylaxis.Objective:This analysis evaluated Berinert Patient Registry data regarding IV pnfC1-INH used as long-term prophylaxis (LTP).Methods:The international registry (2010–2014) collected prospective and retrospective usage, dosing, and safety data on individuals who used pnfC1-INH for any reason.Results:The registry included data on 47 subjects (80.9% female subjects; mean age, 44.8 years), which reflected 4082 infusions categorized as LTP and a total of 430.2 months of LTP administration. The median absolute dose of pnfC1-INH given for LTP was 1000 IU (range, 500–3000 IU), with a median time interval between infusion and a subsequent pnfC1-INH–treated attack of 72.0 hours (range, 0.0–166.4 hours). Fifteen subjects (31.9%) had no pnfC1-INH–treated HAE attacks within 7 days after pnfC1-INH infusion for LTP; 32 subjects (68.1%) experienced 246 attacks, with rates of 0.06 attacks per infusion and 0.57 attacks per month. A total of 81 adverse events were reported in 16 subjects (34.0%) (0.02 events per infusion; 0.19 events per month); only 3 adverse events were considered related to pnfC1-INH (noncardiac chest pain, postinfusion headache, deep vein thrombosis in a subject with an IV port).Conclusion:In this international registry, IV pnf-C1-INH given as LTP for HAE was safe and efficacious, with a low rate of attacks that required pnfC1-INH treatment, particularly within the first several days after LTP administration.

The use of tranexamic acid for on‐demand and prophylactic treatment of hereditary angioedema—A systematic review

“…In certain countries, particularly Japan, TXA is an important treatment option for many patients with HAE, particularly for LTP. Although C1‐INH has been demonstrated to be safe and effective, self‐administration and LTP are not licensed, and accessibility to treatment is challenging for many patients in Japan . In addition, awareness of HAE among physicians in Japan is low and the limited availability of effective therapies increases the burden of HAE .…”

“…31,32 In addition, the long-term safety and efficacy of pdC1-INH have been evaluated using real-world patient registry data, which showed that pdC1-INH administration reduces the rate of attacks and is associated with an excellent safety profile. 33 Recently, SC injection of C1-INH has also been approved for long-term prophylaxis (LTP) in adults and adolescents. Data from the COMPACT trial demonstrated a favorable safety profile and a significantly reduced rate of attacks with self-administered SC C1-INH, which also resulted in near-normal C1-INH levels.…”

“…Similarly, ecallantide and icatibant have demonstrated significantly reduced symptom severity compared with placebo . In addition, the long‐term safety and efficacy of pdC1‐INH have been evaluated using real‐world patient registry data, which showed that pdC1‐INH administration reduces the rate of attacks and is associated with an excellent safety profile . Recently, SC injection of C1‐INH has also been approved for long‐term prophylaxis (LTP) in adults and adolescents.…”

Hereditary Angio-Oedema for Dermatologists

“…Thromboembolic events have rarely been reported in association with plasma-derived C1INH concentrates and seem to occur in patients with underlying risk factors including indwelling catheters [110-112]. Ruconest® was associated with anaphylaxis in a single volunteer allergic to rabbit; however, no further anaphylaxis has been reported in clinical use [113].…”

“…LTP with C1INH concentrate (CSL830 or Cinryze ®) is a very safe and effective approach [110, 111, 121, 122]. An open-label multicentre study in 146 subjects for almost 3 years documented a 93.7% reduction in attack frequency in patients treated with Cinryze® 1,000 units every 3–7 days [111].…”