C1 Inhibitor Activity and Angioedema Attacks in Patients with Hereditary Angioedema.

Hereditary angioedema (HAE) is caused by deficiency or dysfunction in the C1 inhibitor (C1-INH) protein. C1-INH replacement therapy is used to treat patients with HAE to restore the missing or dysfunctional protein. In vitro studies showed that C1-INH inhibits prekallikrein activation and bradykinin formation in a dose-dependent manner when added to the plasma of patients with HAE. HAE is highly variable in clinical presentation, and early studies suggested that there was not a clear relationship between functional C1-INH levels and disease activity. Later, a threshold of approximately 40% functional C1-INH was identified, above which patients' risk of an attack was diminished. Long-term prophylaxis with plasma-derived C1-INH effectively reduces attack frequency and severity. Pharmacokinetic modeling shows that functional C1-INH levels are associated with the relative risk of having an attack. Subcutaneous administration of C1-INH results in consistently high levels of functional C1-INH activity, whereas intravenous administration results in periods of low trough functional C1-INH activity before the next scheduled dose, increasing the risk of an angioedema attack. These studies suggest that measurement of functional C1-INH activity may be useful as a biomarker of the risk of an attack in patients with HAE who are receiving long-term prophylaxis with plasma-derived C1-INH.

Training patients for self-administration of a new subcutaneous C1-inhibitor concentrate for hereditary angioedema.

AIMS: The aim of this study was to provide recommendations for training patients with hereditary angioedema, based on nursing clinical trial experience, to self-administer subcutaneous C1-INH (C1-INH[SC]) used as routine prophylaxis. BACKGROUND: A volume-reduced, subcutaneous C1-INH concentrate (C1-INH(SC); HAEGARDA®; CSL Behring) was recently FDA-approved for the routine prevention of hereditary angioedema attacks. Nurses will play an important role in patient training. DESIGN: Review of a phase 3, randomized, placebo-controlled, double-blind, crossover trial of C1-INH(SC) (COMPACT) and summary of recommendations for training patients based on nurses' "hands-on experience." METHODS: A panel of nurses with clinical trial experience provided recommendations for patient training. RESULTS: Practical suggestions and guidelines were compiled regarding patient selection, product reconstitution and administration and patient follow-up. Successful patient self-administration of C1-INH(SC) can be greatly facilitated by qualified nursing intervention. The information provided in this paper will be useful to nurses anywhere who have an opportunity to interact with patients dealing with hereditary angioedema.

Patient satisfaction and experience with intravenously administered C1-inhibitor concentrates in the United States.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disorder with substantial morbidity and mortality. Despite expanded choices for effective acute treatment, prophylactic options are more limited. Intravenous C1 esterase inhibitor (C1-INH[IV]) is licensed and used to prevent HAE symptoms. OBJECTIVE: To better understand patient experiences with using C1-INH(IV), including level of satisfaction and types and frequency of complications. METHODS: Fifty adult members (≥18 years of age) of the US HAE Association who had HAE type I or II completed a self-administered internet survey. Eligible participants were experiencing at least 1 HAE attack per month and must have been receiving treatment with C1-INH(IV) as prophylaxis or acute therapy. RESULTS: Almost all respondents (n = 47; 94%) were using C1-INH(IV) for HAE prophylaxis. Most patients reported administration of C1-INH(IV) through a peripheral vein (n = 34) and 19 were currently (n = 17) or previously (n = 2) using a central venous port. Most respondents (62%) who used a peripheral vein to administer treatment reported having difficulty finding a usable vein or getting the infusion to work properly at least some of the time. Issues accessing veins, exhausted veins, and frequency of attacks were the main reasons physicians recommended ports to respondents. Although ports allow easier administration of therapy, 47% of respondents with ports experienced problems such as occlusion, thrombosis, and infection. Respondents using C1-INH prophylaxis reported a mean of 2.3 attacks per month during the previous 6 months. CONCLUSION: The survey results identified clinical challenges with IV HAE medication use, including venous access issues and ongoing monthly attack occurrence despite prophylactic C1-INH(IV) administration.