Watt Maureen, Goldgrub Rachel, Malmenäs Mia, Haeussler Katrin
Takeda Development Center Americas, Inc., Lexington, MA 02421, USA.
ICON plc, Insights, Evidence & Value - Health Economics & Epidemiology, Vancouver, British Columbia, Canada.
J Comp Eff Res. 2025 Feb;14(2):e240110. doi: 10.57264/cer-2024-0110. Epub 2025 Jan 21.
To compare the efficacy and safety of lanadelumab versus other approved long-term prophylaxis (LTP) treatments in patients with pediatric hereditary angioedema (HAE) aged <12 years. A systematic literature review was conducted to identify studies of LTP in patients with HAE aged <12 years. Two studies met the inclusion criteria in an indirect treatment comparison of efficacy and safety data in pediatric HAE patients. These were for lanadelumab (SPRING, NCT04070326) and intravenous-C1-esterase inhibitor (C1-INH[IV], NCT02052141). A propensity score analysis used individual patient-level data from both studies in a logistic regression model to estimate inverse probability weights. To avoid convergence issues and an underpowered analysis due to the small sample size (n = 29), the base case was defined as Poisson regression analyses on monthly attack rate adjusting for one covariate (baseline attack rate). Model selection among unadjusted, adjusted and weighted regression models was conducted through the Akaike and Bayesian Information Criteria. Lanadelumab 150 mg every 2 weeks (Q2W) reduced the monthly HAE attack rate by 82.1% versus C1-INH(IV) 1000 IU twice weekly (every 3-4 days [BIW]; rate ratio [RR], 0.1792 [95% CI: 0.0296-1.0853]) and by 88.9% versus C1-INH(IV) 500 IU BIW (RR: 0.1107 [95% CI: 0.0234-0.5239]). Treatment with lanadelumab Q2W reduced the risk of total adverse events by 56.2% versus C1-INH(IV) 1000 IU BIW (RR:0.4377 [95% CI: 0.1536-1.2469]) and by 66.0% versus C1-INH(IV) 500 IU BIW (RR: 0.3401 [95% CI: 0.1234-0.9371]). This exploratory analysis suggested a trend toward greater efficacy and fewer adverse events with lanadelumab 150 mg Q2W compared with C1-INH(IV) BIW 1000 IU and 500 IU in pediatric patients with HAE. Future studies could potentially assess larger samples over longer periods of time for the long-term preventative efficacy, safety and tolerability of lanadelumab and C1-INH(IV).
比较lanadelumab与其他已批准的长期预防（LTP）治疗方案在12岁以下儿童遗传性血管性水肿（HAE）患者中的疗效和安全性。
进行了一项系统的文献综述，以确定12岁以下HAE患者的LTP研究。两项研究符合纳入标准，用于对儿科HAE患者的疗效和安全性数据进行间接治疗比较。这两项研究分别是关于lanadelumab（SPRING，NCT04070326）和静脉注射C1酯酶抑制剂（C1-INH[IV]，NCT02052141）。倾向评分分析使用了两项研究中个体患者水平的数据，通过逻辑回归模型来估计逆概率权重。为避免由于样本量小（n = 29）导致的收敛问题和分析效能不足，基础病例定义为对每月发作率进行泊松回归分析，并对一个协变量（基线发作率）进行调整。通过赤池信息准则和贝叶斯信息准则在未调整、调整和加权回归模型中进行模型选择。与每周两次（每3 - 4天[BIW]）注射1000 IU的C1-INH(IV)相比，每2周（Q2W）注射150 mg的lanadelumab可使HAE每月发作率降低82.1%（率比[RR]，0.1792 [95%置信区间：0.0296 - 1.0853]）；与每周两次注射500 IU的C1-INH(IV)相比，可使发作率降低88.9%（RR：0.1107 [95%置信区间：0.0234 - 0.5239]）。与每周两次注射1000 IU的C1-INH(IV)相比，每2周注射lanadelumab可使总不良事件风险降低56.2%（RR：0.4377 [95%置信区间：0.1536 - 1.2469]）；与每周两次注射500 IU的C1-INH(IV)相比，可使不良事件风险降低66.0%（RR：0.3401 [95%置信区间：0.1234 - 0.9371]）。这项探索性分析表明，在儿科HAE患者中，与每周两次注射1000 IU和500 IU的C1-INH(IV)相比，每2周注射150 mg的lanadelumab有疗效更高、不良事件更少的趋势。未来的研究可能会在更长时间内评估更大样本，以研究lanadelumab和C1-INH(IV)的长期预防疗效、安全性和耐受性。
