Takeda Pharmaceuticals International AG, A Takeda Company, Zurich, Switzerland.
ICON plc, Stockholm, Sweden.
Drugs R D. 2021 Mar;21(1):113-121. doi: 10.1007/s40268-021-00337-4. Epub 2021 Mar 1.
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.
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).
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.
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.
遗传性血管性水肿（HAE）伴 C1 酯酶抑制剂（C1-INH）缺乏症是一种罕见疾病，与影响皮下或黏膜下组织的疼痛、潜在致命的肿胀发作有关。HAE 发作在患者的一生中反复发作，严重程度和频率不可预测；一些患者需要长期预防治疗。由于缺乏头对头研究，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。
我们使用安慰剂对照 HELP 研究（评估接受每 2 或 4 周 300mg 拉那芦单抗治疗的患者）和为期 12 周、平行臂、交叉 CHANGE 研究（评估静脉注射 C1-INH）的数据进行 ITC。感兴趣的结果是攻击率比（ARR）和从第 0 天（TTA0）和第 70 天（TTA70）后的攻击时间。使用了两种 ITC 方法：一种是贝叶斯方法，使用研究结果更新非信息先验分布到相对治疗效果的后验分布；另一种是使用 HELP 和 CHANGE 中的患者水平数据生成泊松回归（用于 ARR）和 Cox 模型（用于 TTA0 和 TT70）的频率主义方法。
贝叶斯和频率主义分析均表明，拉那芦单抗与静脉注射 C1-INH 相比，降低了 HAE 的攻击率 46-73%。与静脉注射 C1-INH 相比，第 0 天之后首次发作的风险在静脉注射 C1-INH 和两种拉那芦单抗剂量之间是相似的；与 C1-INH 相比，每 2 周接受 300mg 拉那芦单抗治疗的患者，第 70 天之后首次发作的风险降低了 81-83%。
这两种 ITC 方法的研究结果支持拉那芦单抗在降低 HAE 发作率和延长 HAE 患者无发作间期方面的良好疗效。
