使用拉那度单抗对青少年遗传性血管性水肿发作进行长期预防。

Long-term prevention of hereditary angioedema attacks with lanadelumab in adolescents.

作者信息

Craig Timothy, Tachdjian Raffi, Bernstein Jonathan A, Anderson John, Nurse Christina, Watt Maureen, Yu Ming, Juethner Salomé

机构信息

Allergy, Asthma, and Immunology Section, Departments of Medicine, Pediatrics, and Biomedical Sciences, Director ACARE International Hereditary Angioedema Resource Center, Penn State University, Hershey, Pennsylvania; Department of Allergy and Immunology, Vinmec International Hospital, Times City, Hanoi, Vietnam.

Division of Allergy, Immunology, and Rheumatology, University of California, Los Angeles, California.

出版信息

Ann Allergy Asthma Immunol. 2024 Dec;133(6):712-719.e1. doi: 10.1016/j.anai.2024.08.001. Epub 2024 Aug 10.

DOI:10.1016/j.anai.2024.08.001

PMID:39128590

Abstract

BACKGROUND

Lanadelumab was well tolerated and effective in preventing hereditary angioedema (HAE) attacks in the phase 3, double-blind, placebo-controlled Hereditary angioEdema Long-term Prophylaxis (HELP) study and subsequent HELP open-label extension (OLE) study (NCT02741596).

OBJECTIVE

To evaluate outcomes from HELP OLE for adolescent patients aged 12 to 17 years.

METHODS

The HELP OLE study comprised patients who completed the HELP study (rollovers) and new eligible (lanadelumab-naive) patients. Rollovers received a single dose of lanadelumab 300 mg at the last HELP study visit (day 0). Treatment was then paused until patients experienced their first investigator-confirmed HAE attack, after which lanadelumab 300 mg was administered every 2 weeks for up to 33 months (4 wk/mo). Lanadelumab-naive patients received lanadelumab 300 mg every 2 weeks from day 0. Patient-reported outcomes included Angioedema Quality of Life Questionnaire. Safety was monitored throughout the study.

RESULTS

The subgroup analysis included 21 patients (8 rollovers and 13 lanadelumab-naive patients); 95.2% completed at least 30 months in the study. The mean (SD) monthly attack rate decreased from 1.58 (1.0) at baseline to 0.11 (0.2) during treatment (mean, 94.7% reduction). A total of 8 (38.1%) patients were attack-free during treatment and, on average, 99.1% of days were attack-free (mean, 27.7 d/mo). Patients reported a mean (SD) Angioedema Quality of Life Questionnaire total score of 27.5 (17.5) at baseline vs 7.5 (13.2) at the end of the study. There were 12 (57.1%) patients who reported treatment-related treatment-emergent adverse events; however, there were no treatment-related serious adverse events.

CONCLUSION

Lanadelumab provided long-term efficacy in preventing HAE attacks, was associated with clinically meaningful improvements in health-related quality of life and high levels of treatment satisfaction, and was well tolerated in adolescent patients.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT02741596.

摘要

背景

在3期双盲、安慰剂对照的遗传性血管性水肿长期预防（HELP）研究以及随后的HELP开放标签扩展（OLE）研究（NCT02741596）中，拉那度单抗耐受性良好且能有效预防遗传性血管性水肿（HAE）发作。

目的

评估HELP OLE研究中12至17岁青少年患者的治疗结果。

方法

HELP OLE研究包括完成HELP研究的患者（转入患者）和新的符合条件（未使用过拉那度单抗）的患者。转入患者在HELP研究的最后一次访视（第0天）接受一剂300mg拉那度单抗。然后暂停治疗，直到患者经历首次经研究者确认的HAE发作，之后每2周给予300mg拉那度单抗，持续长达33个月（每月4周）。未使用过拉那度单抗的患者从第0天开始每2周接受300mg拉那度单抗治疗。患者报告的结局包括血管性水肿生活质量问卷。在整个研究过程中监测安全性。

结果

亚组分析纳入了21例患者（8例转入患者和13例未使用过拉那度单抗的患者）；95.2%的患者完成了至少30个月的研究。平均（标准差）每月发作率从基线时的1.58（1.0）降至治疗期间的0.11（0.2）（平均降低94.7%）。共有8例（38.1%）患者在治疗期间无发作，平均99.1%的天数无发作（平均每月27.7天）。患者报告的血管性水肿生活质量问卷总分在基线时平均（标准差）为27.5（17.5），在研究结束时为7.5（13.2）。有12例（57.1%）患者报告了与治疗相关的治疗中出现的不良事件；然而，没有与治疗相关的严重不良事件。