Maurer Marcus, Lumry William R, Li H Henry, Aygören-Pürsün Emel, Busse Paula J, Jacobs Joshua, Nurse Christina, Ahmed Mariam A, Watt Maureen, Yu Ming
Institute of Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany.
Allergy & Asthma Research Center, Dallas, Texas.
J Allergy Clin Immunol Pract. 2024 Jan;12(1):201-211.e6. doi: 10.1016/j.jaip.2023.09.009. Epub 2023 Sep 18.
Symptoms of hereditary angioedema (HAE) often first occur during childhood, and HAE attacks in children can be severe and substantially affect health-related quality of life (HRQoL). However, there are no approved long-term prophylaxis treatments for children aged less than 6 years.
The SPRING Study (NCT04070326) evaluated the safety, pharmacokinetics, and efficacy of lanadelumab and HRQoL in patients aged 2 to less than 12 years.
Over 52 weeks of treatment, patients aged 2 to less than 6 years received lanadelumab 150 mg every 4 weeks (Q4W) and patients aged 6 to less than 12 years received 150 mg every 2 weeks (Q2W) but could switch to Q4W if they were attack-free for 26 weeks.
We enrolled 21 patients (aged 2 to less than 6 years: n = 4; aged 6 to less than 12 years: n = 17), 20 of whom completed the study. There were no reported serious treatment-emergent adverse events or discontinuations resulting from such events. Treatment-emergent adverse events were reported for 17 patients (81.0%). The most common TEAE was injection site pain. Overall systemic exposure was comparable for both age groups. The mean (SD) attack rate during treatment decreased by 94.8% from baseline (1.84 [1.53] to 0.08 [0.17] attacks/mo), and 16 (76.2%) patients were attack-free. The attack rate reduction in both age groups was similar during the first 26-week fixed-dosing treatment. Seven patients switched from Q2W to Q4W and remained attack-free. A large, clinically meaningful increase in the Pediatric Quality of Life Inventory Generic Core Scale Total Score and a large increase in the Pediatric Quality of Life Inventory Generic Core Scale-Family Impact Module Total Score from baseline to end of study (better HRQoL) were observed.
Findings support safety, efficacy, and improved HRQoL with lanadelumab 150 mg Q2W and Q4W regimens for the prevention of HAE attacks in patients aged 2 to less than 12 years.
遗传性血管性水肿（HAE）症状通常在儿童期首次出现，儿童期的HAE发作可能很严重，并会显著影响健康相关生活质量（HRQoL）。然而，对于6岁以下儿童，尚无获批的长期预防治疗方法。
SPRING研究（NCT04070326）评估了lanadelumab在2至未满12岁患者中的安全性、药代动力学、疗效及HRQoL。
在超过52周的治疗期间，2至未满6岁的患者每4周接受150mg lanadelumab治疗（每4周一次），6至未满12岁的患者每2周接受150mg治疗（每2周一次），但如果他们在26周内无发作，则可改为每4周一次。
我们纳入了21例患者（2至未满6岁：n = 4；6至未满12岁：n = 17），其中20例完成了研究。未报告严重的治疗中出现的不良事件或由此类事件导致的停药情况。17例患者（81.0%）报告了治疗中出现的不良事件。最常见的治疗中出现的不良事件是注射部位疼痛。两个年龄组的总体全身暴露水平相当。治疗期间的平均（标准差）发作率较基线下降了94.8%（从1.84[1.53]次/月降至0.08[0.17]次/月），16例（76.2%）患者无发作。在最初26周的固定剂量治疗期间，两个年龄组的发作率降低情况相似。7例患者从每2周一次改为每4周一次，且仍无发作。从基线到研究结束，观察到儿童生活质量量表通用核心量表总分有大幅的、具有临床意义的增加，以及儿童生活质量量表通用核心量表-家庭影响模块总分有大幅增加（HRQoL改善）。
研究结果支持150mg lanadelumab每2周一次和每4周一次的方案在预防2至未满12岁患者HAE发作方面的安全性、有效性及对HRQoL的改善作用。
