Jonathan A Bernstein1, Anurag Relan2, Joseph R Harper2, Marc Riedl3. 1. Division of Immunology, Allergy and Rheumatology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: bernstja@ucmail.uc.edu. 2. Department of Clinical Research and Medical Affairs, Pharming Healthcare Inc., Berkeley Heights, New Jersey. 3. Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California-San Diego, La Jolla, California.
Abstract
BACKGROUND: Symptoms of hereditary angioedema (HAE) attacks can recur soon after initial treatment; the durability of response for recombinant human C1 esterase inhibitor (rhC1INH) treatment is unknown. OBJECTIVE: To examine the efficacy and durability of rhC1INH for acute HAE attacks. METHODS: In this pooled post hoc analysis of 2 trials, patients with type I or II HAE (functional C1INH levels <50% of normal) and a baseline visual analog scale score of at least 50 mm were included if they had received at least 1 intravenous dose of 50 IU/kg of rhC1INH. Response was defined as symptom relief within 4 hours after treatment with persistence (≥20-mm decrease in visual analog scale scores [0 mm {"no symptoms at all"} to 100 mm {"extremely disabling"}] at 2 consecutive time points) during the 4 hours. Durability was the response without an increase of at least 20 mm in the minimum post-treatment visual analog scale score up to 24 hours. Recurrence and new attack symptoms were determined for patients with 72-hour post-treatment data. RESULTS: Data were analyzed for 127 patients treated with 50 IU/kg of rhC1INH in 2 studies. Most attacks (90.7%) responded within 4 hours, with differences in response rates among attack locations (61.5%-94.4%). The median time to the beginning of symptom relief was 75.0 minutes (95% confidence interval 65.0-80.0). No relapse occurred during 24 hours for attacks that initially responded. Only 7.1% of attacks were associated with symptom recurrence within 72 hours of initial rhC1INH treatment. CONCLUSION: This integrated analysis supports the efficacy of rhC1INH for treatment of acute HAE across multiple attacks, with a sustained response for at least 3 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT00225147 and NCT00262301.
BACKGROUND: Symptoms of hereditary angioedema (HAE) attacks can recur soon after initial treatment; the durability of response for recombinant humanC1 esterase inhibitor (rhC1INH) treatment is unknown. OBJECTIVE: To examine the efficacy and durability of rhC1INH for acute HAE attacks. METHODS: In this pooled post hoc analysis of 2 trials, patients with type I or II HAE (functional C1INH levels <50% of normal) and a baseline visual analog scale score of at least 50 mm were included if they had received at least 1 intravenous dose of 50 IU/kg of rhC1INH. Response was defined as symptom relief within 4 hours after treatment with persistence (≥20-mm decrease in visual analog scale scores [0 mm {"no symptoms at all"} to 100 mm {"extremely disabling"}] at 2 consecutive time points) during the 4 hours. Durability was the response without an increase of at least 20 mm in the minimum post-treatment visual analog scale score up to 24 hours. Recurrence and new attack symptoms were determined for patients with 72-hour post-treatment data. RESULTS: Data were analyzed for 127 patients treated with 50 IU/kg of rhC1INH in 2 studies. Most attacks (90.7%) responded within 4 hours, with differences in response rates among attack locations (61.5%-94.4%). The median time to the beginning of symptom relief was 75.0 minutes (95% confidence interval 65.0-80.0). No relapse occurred during 24 hours for attacks that initially responded. Only 7.1% of attacks were associated with symptom recurrence within 72 hours of initial rhC1INH treatment. CONCLUSION: This integrated analysis supports the efficacy of rhC1INH for treatment of acute HAE across multiple attacks, with a sustained response for at least 3 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT00225147 and NCT00262301.