拉那度单抗长期预防遗传性血管性水肿的持续有效性、耐受性和安全性：前瞻性4期非干预性EMPOWER真实世界研究
Sustained Effectiveness, Tolerability, and Safety of Long-Term Prophylaxis with Lanadelumab in Hereditary Angioedema: The Prospective, Phase 4, Noninterventional EMPOWER Real-World Study.
作者信息
Bernstein Jonathan A, Betschel Stephen D, Busse Paula J, Banerji Aleena, Wedner H James, Manning Michael, Zaragoza-Urdaz Rafael H, Anderson John, Gagnon Remi, Baptist Alan P, Soteres Daniel, Lumry William R, Craig Timothy, Petroni Daniel, Hsu F Ida, Nova Estepan Daniel, Juethner Salomé, Watt Maureen, Khutoryansky Natalie, Zuraw Bruce L
机构信息
Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML#563, Cincinnati, OH, 45267-0563, USA.
Advanced Allergy Services LLC, Cincinnati, OH, USA.
出版信息
Adv Ther. 2025 Jun 12. doi: 10.1007/s12325-025-03226-3.
INTRODUCTION
Lanadelumab is approved for long-term prophylaxis of hereditary angioedema (HAE) attacks in patients aged ≥ 2 years in the USA and aged ≥ 12 years in Canada. The EMPOWER Study (NCT03845400) evaluated the real-world effectiveness and safety of lanadelumab in male and female patients with HAE due to C1 inhibitor deficiency type 1 or 2 from the USA and Canada. Here, we report final, up to 36-month, data.
METHODS
Patients aged ≥ 12 years were classified as newly treated with lanadelumab or established on lanadelumab (receiving < 4 and ≥ 4 lanadelumab doses at enrollment, respectively). The primary objective was effectiveness of lanadelumab as measured by HAE attack rate before and after lanadelumab initiation. Safety data were collected.
RESULTS
A total of 109 patients received ≥ 1 lanadelumab dose and had ≥ 1 post-baseline safety assessment. Patients were 40.9 (17.4) years of age (mean [standard deviation (SD)]), majority (72/109; 66.1%) female, 37/109 (33.9%) male, and over 90% white. Patients newly treated with and established on lanadelumab received lanadelumab for 737.7 (374.5) (mean [SD]) and 907.1 (469.3) days, respectively, during the study. In patients newly treated with lanadelumab, the mean (95% confidence interval) observed attack rate (attacks/month) decreased by 85% after lanadelumab initiation, from 1.42 (0.34-2.50) pre-lanadelumab to 0.20 (0.02-0.38) post-lanadelumab initiation (cumulative period). Patients established on lanadelumab had an observed attack rate of 0.20 (0.10-0.30) during 36 months' follow-up. Of 154 treatment-emergent adverse events (TEAEs), no injection site reactions were reported and 6 (in 2 patients) were considered related to lanadelumab; no lanadelumab-related TEAEs were serious.
CONCLUSION
Real-world data from EMPOWER showed marked HAE attack rate reduction up to 36 months after initiating lanadelumab in patients newly treated with lanadelumab and maintenance of low attack rates in patients established on lanadelumab. No new safety signals were identified.
TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT03845400. Graphical abstract available for this article.
引言
在美国，拉那度单抗被批准用于≥2岁患者遗传性血管性水肿（HAE）发作的长期预防，在加拿大则被批准用于≥12岁患者。EMPOWER研究（NCT03845400）评估了拉那度单抗在美国和加拿大1型或2型C1抑制剂缺乏所致HAE的男性和女性患者中的真实疗效和安全性。在此，我们报告长达36个月的最终数据。
方法
≥12岁的患者被分类为新接受拉那度单抗治疗或已接受拉那度单抗治疗（入组时分别接受<4剂和≥4剂拉那度单抗）。主要目标是通过拉那度单抗开始治疗前后的HAE发作率来衡量拉那度单抗的疗效。收集安全性数据。
结果
共有109名患者接受了≥1剂拉那度单抗并进行了≥1次基线后安全性评估。患者年龄为40.9（17.4）岁（均值[标准差（SD）]），大多数（72/109；66.1%）为女性，37/109（33.9%）为男性，超过90%为白人。在研究期间，新接受拉那度单抗治疗和已接受拉那度单抗治疗的患者分别接受拉那度单抗治疗737.7（374.5）（均值[SD]）天和907.1（469.3）天。在新接受拉那度单抗治疗的患者中，拉那度单抗开始治疗后，观察到的平均（95%置信区间）发作率（发作次数/月）从拉那度单抗治疗前的1.42（0.34 - 2.50）降至拉那度单抗开始治疗后的0.20（0.02 - 0.38），下降了85%（累积期）。已接受拉那度单抗治疗的患者在36个月的随访期间观察到的发作率为0.20（0.10 - 0.30）。在154例治疗中出现的不良事件（TEAE）中，未报告注射部位反应，6例（2名患者）被认为与拉那度单抗有关；没有与拉那度单抗相关的TEAE是严重的。
结论
EMPOWER研究的真实数据显示，新接受拉那度单抗治疗的患者在开始使用拉那度单抗后长达36个月HAE发作率显著降低，且已接受拉那度单抗治疗的患者维持低发作率。未发现新的安全信号。
试验注册
ClinicalTrials.gov，标识符NCT03845400。本文提供图形摘要。
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