The Effect of Weight on the Efficacy and Safety of C1 Esterase Inhibitor Concentrate for the Treatment of Acute Hereditary Angioedema

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• 作者：Jonathan A. Bernstein ; MD¹ ; ^{bernstja@ucmail.uc.edu" class="auth_mail} ; Thomas Machnig ; MD² ; Heinz-Otto Keinecke ; MSc³ ; Glenn J. Whelan ; PharmD² ; Timothy J. Craig ; DO⁴
• 关键词：body mass index ; C1 esterase inhibitor ; dosing ; hereditary angioedema ; obesity ; pharmacokinetics
• 刊名：Clinical Therapeutics
• 出版年：1 April, 2014
• 年：2014
• 卷：36
• 期：4
• 页码：518-525
• 全文大小：213 K

文摘

Background

Despite the worldwide obesity epidemic, there have been very few studies investigating the influence of body weight on treatment dosing and outcomes in patients with hereditary angioedema (HAE).

Objective

The purpose of this analysis was to determine whether the standard weight-based dosing recommendation of C1 esterase inhibitor (C1-INH) concentrate (20 IU/kg) is adequate in HAE patients with a high body mass index (BMI).

Methods

Data from patients treated for HAE attacks with 20聽IU/kg of C1-INH concentrate were retrospectively analyzed from the open-label IMPACT2 study (International聽Multicenter聽Prospective聽Angioedema C1-INH Trial). Patients were categorized according to BMI as being normal body weight, overweight, or obese. Efficacy end points were time to onset of symptom relief and time to complete resolution of symptoms. The safety profile was evaluated according to adverse events occurring within 7 to 9 days of treatment.

Results

Of 57聽patients, 24 (42%) were of normal body weight, 20聽(35%) were overweight, and 13聽(23%) were obese. Median (95% CI) time to onset of symptom relief was 0.37聽hour (0.29-0.57) in normal-weight patients, 0.48聽hour (0.39-0.53) in overweight patients, and 0.58聽hour (0.41-0.94) in obese patients. Median time (95% CI) to complete resolution of symptoms was 15.2聽hours (9.3-23.2) in normal-weight patients, 22.6聽hours (11.3-44.6) in overweight patients, and 11.0聽hours (5.6-23.6) in obese patients (differences not significant). There were no relevant differences in the incidence of adverse events in normal-weight patients (54%), overweight patients (30%), and obese patients (54%).

Conclusions

Treatment of HAE attacks with weight-based doses of C1-INH concentrate provided reliable treatment response, regardless of body weight, in these patients with HAE.