Tolerability and Effectiveness of 17-α-Alkylated Androgen Therapy for Hereditary Angioedema: A Re-examination.

BACKGROUND: Hereditary angioedema (HAE) is a genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling. 17-α-Alkylated androgens (AA) have been used prophylactically to reduce HAE severity, but there are many questions about the efficacy and tolerability of AA. OBJECTIVE: The objective of this study was to investigate the tolerability and effectiveness of AA therapy in a large cohort of patients with HAE. METHODS: We performed a retrospective cross-sectional study on 650 subjects with HAE utilizing a one time, anonymous, web-based survey. Based on an initial questionnaire, patients were routed to one of the following questionnaires: currently using AA, previously used but discontinued AA, or never used AA. RESULTS: Statistical analysis revealed that androgens decreased attack frequency and severity in previous AA users (P < .0001) and current AA users (P < .0001). Substantial variability in the effectiveness was observed. Users who discontinued AA reported significantly lesser benefit. No dose effect was seen for the beneficial effect of AA; however, almost all users reported frequent side effects that were dose related and often severe. CONCLUSIONS: AA therapy is usually effective for the treatment of HAE although a substantial fraction of patients with HAE do not achieve adequate benefit. In contrast, the side effects of AA are seen in almost all subjects who take the medicines. If used, AA should only be recommended in the lowest effective and tolerated dose for carefully selected patients.

Pediatric Hereditary Angioedema: Onset, Diagnostic Delay, and Disease Severity.

Hereditary angioedema (HAE) typically presents in childhood. Large gaps remain in our understanding of the natural history of HAE during childhood. We examined age of onset, delay in diagnosis, androgen exposure, and their influence on ultimate disease severity in a large cohort of patients with HAE. Median age of first swelling was 11 years with a median age at diagnosis of 19 years. Earlier onset of symptoms correlated with longer delays in diagnosis (P < .001) and predicted a more severe disease course, including increased number of attacks per year (P = .0009) and hospital admissions (P = .009). Earlier age of onset also significantly correlated with increased perceived HAE severity (P = .0002), negative overall life impact (P < .0001), and use of anabolic androgen. Our observations highlight the importance of early HAE diagnosis and suggest the necessity of a disease management plan once the diagnosis has been made.

Safety and efficacy of physician-supervised self-managed C1 inhibitor replacement therapy.

BACKGROUND: C1 inhibitor (C1INH) has recently been approved in the USA for the treatment of acute attacks in hereditary angioedema (HAE) patients. The literature suggests that treatment with C1INH is most effective when administered early in an attack. Home infusion of C1INH allows for the earliest possible intervention since patients can initiate therapy at the first sign of symptoms. METHODS: We performed an observational, prospective study on 39 subjects with HAE utilizing two groups of patients: one receiving on-demand C1INH replacement therapy in a medical facility and the other self-managing on-demand C1INH replacement therapy in the home setting under the supervision of a treating physician. All subjects completed online questionnaires weekly for 8 weeks. RESULTS: There were statistically significant decreases in attack duration (p < 0.0001), pain medication use (p < 0.0001) and graded attack severity (p < 0.005) in the subjects who received C1INH in the home setting versus the clinic-based group. Attack frequency was similar between the groups. The home group experienced more frequent injection-related side effects; however, the clinic group noted more severe adverse events from C1INH. CONCLUSION: Physician-supervised self-managed C1INH replacement therapy is a safe and effective treatment for patients with HAE with potential benefits in diminishing attack duration and attack severity.