Background

Hereditary angioedema (HAE) with C1-esterase inhibitor (C1-INH) deficiency is a rare disease associated with painful, potentially fatal swelling episodes affecting subcutaneous or submucosal tissues. HAE attacks recur with unpredictable severity and frequency throughout patients’ lives; long-term prophylaxis is essential for some patients. In the absence of head-to-head studies, indirect treatment comparison (ITC) of long-term prophylactic agents is a valid approach to evaluate comparative efficacy.

Methods

We conducted an ITC using data from the placebo-controlled HELP study (assessing patients receiving lanadelumab 300 mg every 2 or 4 weeks) and the 12-week, parallel arm, crossover CHANGE study (assessing intravenous C1-INH). Outcomes of interest were attack rate ratio (ARR) and time to attack after day 0 (TTA0) and after day 70 (TTA70). Two ITC methodologies were used: a Bayesian approach using study results to update non-informative prior distributions to posterior distributions on relative treatment effects, and a frequentist approach using patient-level data from HELP and CHANGE to generate Poisson regressions (for ARR) and Cox models (for TTA0 and TT70).

Results

Both Bayesian and frequentist analyses suggested that lanadelumab reduced HAE attack rate by 46–73% versus intravenous C1-INH. Relative to intravenous C1-INH, risk of first attack after day 0 was comparable between intravenous C1-INH and both lanadelumab doses; risk of first attack after day 70 was reduced by 81–83% with lanadelumab 300 mg every 2 weeks, compared with C1-INH.

Conclusions

Findings from these two ITC methodologies support the favorable efficacy of lanadelumab in reducing the HAE attack rate and extending attack-free intervals in patients with HAE.

中文翻译：

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使用帮助和变更研究的数据对Lanadelumab和静脉注射的C1-INH进行间接比较：贝叶斯和频度分析

背景

伴有C1酯酶抑制剂（C1-INH）缺乏的遗传性血管性水肿（HAE）是一种罕见的疾病，与痛苦的，可能致命的肿胀发作有关，并影响皮下或粘膜下组织。在患者一生中，HAE发作的严重性和频率难以预测。长期预防对某些患者至关重要。在缺乏直接研究的情况下，长期预防药物的间接治疗比较（ITC）是评估比较疗效的有效方法。

方法

我们使用安慰剂对照的HELP研究（评估每2或4周接受300 mg lanadelumab的患者）和12周平行双臂交叉CHANGE研究（评估静脉内C1-INH）的数据进行了ITC。感兴趣的结果是攻击率比率（ARR）和第0天（TTA0）和第70天之后（TTA70）之后的攻击时间。使用了两种ITC方法：一种贝叶斯方法，利用研究结果将相对于治疗效果的非信息性先前分布更新为后部分布；以及一种频频方法，使用来自HELP和CHANGE的患者水平数据来生成Poisson回归（针对ARR）和Cox型号（适用于TTA0和TT70）。

结果

贝叶斯和频频分析均表明，与静脉内C1-INH相比，lanadelumab可使HAE发作率降低46-73％。相对于静脉注射C1-INH，第0天后首次发作的风险在静脉注射C1-INH和两种lanadelumab剂量之间均具有可比性。与C1-INH相比，每两周服用lanadelumab 300 mg，第70天后首次发作的风险降低81-83％。

结论

这两种ITC方法论的发现支持lanadelumab在降低HAE发作率和延长HAE患者的无发作间隔方面的有利疗效。