Treatment Of Angioedema Attacks Research Articles

US Hereditary Angioedema Association Medical Advisory Board 2013 Recommendations for the Management of Hereditary Angioedema Due to C1 Inhibitor Deficiency

The treatment of hereditary angioedema (HAE) has undergone dramatic changes as newer medicines have become available in recent years. Optimal care of these patients requires a comprehensive management plan. Although several consensus papers have been published concerning the diagnosis and treatment of HAE, guidelines for a comprehensive management plan have not been developed. To develop state-of-the-art recommendations for the treatment and management of HAE due to C1 inhibitor (C1INH) deficiency in the United States. Members of the US Hereditary Angioedema Association Medical Advisory Board began by reviewing the literature concerning treatment of HAE. Preliminary recommendations were developed based on the literature review, discussions in a face-to-face meeting, and refinements in a series of drafts. Final recommendations reflect the unanimous consensus of the medical advisory board and the US Hereditary Angioedema Association leadership. Recommendations are provided regarding a comprehensive care plan for HAE, including the following: development of an overall management plan, treatment of angioedema attacks, prophylactic treatment, and patient monitoring. A comprehensive individualized management plan developed between an expert HAE physician and the patient, in collaboration with local medical providers and emergency departments, can provide patients with the best opportunity to lead a normal life.

Recombinant Human C1 Inhibitor (Conestat Alfa)

Conestat alfa is a recombinant human C1 inhibitor used in the treatment of angioedema attacks in patients with hereditary angioedema (HAE). Patients with type I or II HAE have a deficiency in functional C1 inhibitor, which is an important regulator of complement and contact system activation. The therapeutic efficacy of conestat alfa in the treatment of angioedema attacks in patients with HAE was evaluated in two similar randomized, double-blind, placebo-controlled trials conducted in North America and Europe. The randomized controlled phases of both studies were closed after interim analyses provided compelling evidence of statistically significant positive efficacy findings and showed no apparent adverse safety findings. Results of the pooled analysis of the two trials showed that conestat alfa provided significantly faster initial relief of symptoms than placebo. The median time to the beginning of relief of symptoms (primary endpoint) was 66 minutes with conestat alfa 100 units/kg, 122 minutes with conestat alfa 50 units/kg, and 495 minutes with placebo. Conestat alfa was also statistically superior to placebo for the secondary endpoint of median time to minimal symptoms, with values of 266, 247, and 1210 minutes for the respective treatment groups. On the basis of data from open-label extension studies and integrated analyses of clinical trial data, conestat alfa has demonstrated efficacy in the treatment of repeated HAE attacks and in patients with potentially life-threatening HAE attacks with involvement of the upper airways. Conestat alfa was generally well tolerated in clinical trials, with the most frequently reported adverse event being headache. In the two randomized controlled trials, headache and vertigo were the only adverse events deemed to be related to study treatment.

Recombinant Human C1 Inhibitor (Conestat Alfa)

Conestat alfa is a recombinant human C1 inhibitor used in the treatment of angioedema attacks in patients with hereditary angioedema (HAE). Patients with type I or II HAE have a deficiency in functional C1 inhibitor, which is an important regulator of complement and contact system activation.

Target levels of functional C1‐inhibitor in hereditary angioedema

Hereditary angioedema (HAE) is a heterozygous deficiency of first component of complement-inhibitor (C1INH). Insufficient C1INH activity leads to uncontrolled activation of plasma cascade systems, which results in acute angioedema attacks in patients with HAE. Plasma-derived or recombinant C1INH products are approved for the treatment of such angioedema attacks. The target level of C1INH activity needed to achieve optimal efficacy, however, remains unknown. We determined the plasma level of C1INH associated with optimal clinical efficacy in the treatment of angioedema attacks. Efficacy and pharmacokinetic data were reviewed from recently published placebo-controlled randomized trials in the treatment of HAE with either plasma-derived or recombinant C1INH products, tested at various doses. A dose-dependent effect was observed on time to the beginning of relief of symptoms, on time to resolution of symptoms, and on the response rate within 4 h. Optimal efficacy of C1INH therapy is achieved at doses ≥50 U/kg. This dose increases plasma C1INH activity in almost all patients to values ≥0.7 U/ml (70% of normal), the lower limit of the normal range. The differences in half-lives of the various C1INH products do not have an obvious effect on clinical efficacy. A review of the efficacy and pharmacokinetic data from recently published controlled studies in the treatment of HAE attacks suggests that efficacy of C1INH therapy is optimal when C1INH activity levels are restored to the normal range.

Long-term follow up analysis of nadroparin for hereditary angioedema. A preliminary report

Hereditary angioedema is caused by a C1-inhibitor deficiency. It is a life-threatening disease. Its management includes treating acute attacks, short-term prophylaxis, and long-term prophylaxis. We report our experience with nadroparin for the short-term prophylaxis and treatment of angioedema attacks. We indicated treatment with nadroparin 0.3–0.6 mL SC 20 min after the onset of prodromes, then every 8–12 h for 1 day; short-term prophylaxis with 0.3–0.6 mL 1 h before a triggering event and then every 12–24 h for 1 more day. For children, treatment included 0.3 mL SC 20 min after the onset of prodromes, then every 12–24 h for 1 day; short-term prophylaxis was 0.3 mL 1 h before a triggering event and 1 more dose after 24 h. For the treatment, a complete response was considered when nadroparin totally stopped an acute attack within 2 h after injection. Partial response was considered if after 2 h analgesics and/or other therapy were required. Failure was established if after 4 h no response was obtained and fresh frozen plasma and other in-patient measures were required. For short-term prophylaxis, only complete responses and failures were considered. We included 29 adults and 5 children. Functional C1-inhibitor and C4 levels rose after nadroparin. We recorded 256 treatments (89.8% complete responses, 8.2% partial responses, and 1.9% failures), and 102 short-term prophylactic regimens (90.2% complete responses, and 9.8% failures). We found 38 mild adverse events without severe hemorrhagic episodes. If our results are reproduced subsequently, nadroparin may be an alternative for the treatment and short-term prophylaxis of angioedema attacks.