干旱区生态环境知识资源中心(Arid): Efficacy and Safety of Donidalorsen for Hereditary Angioedema

Arid

DOI	10.1056/NEJMoa2402478
	Efficacy and Safety of Donidalorsen for Hereditary Angioedema
	Riedl, Marc A.; Tachdjian, Raffi; Lumry, William R.; Craig, Timothy; Karakaya, Gul; Gelincik, Asli; Stobiecki, Marcin; Jacobs, Joshua S.; Gokmen, Nihal M.; Reshef, Avner; Gompels, Mark M.; Manning, Michael E.; Bordone, Laura; Newman, Kenneth B.; Treadwell, Sabrina; Wang, Sophie; Yarlas, Aaron; Cohn, Danny M.
通讯作者	Cohn, DM
来源期刊	NEW ENGLAND JOURNAL OF MEDICINE
ISSN	0028-4793
EISSN	1533-4406
出版年	2024
卷号	391 期号:1 页码:21-31
英文摘要	Background Hereditary angioedema is a rare disorder characterized by episodic, potentially life-threatening swelling caused by kallikrein-kinin dysregulation. Long-term prophylaxis can stabilize this system. Donidalorsen, an antisense oligonucleotide, specifically reduces prekallikrein expression. Methods In this phase 3, double-blind, randomized trial, we assigned patients with hereditary angioedema to receive donidalorsen (80 mg subcutaneously) or placebo once every 4 or 8 weeks. The primary end point was the time-normalized number of investigator-confirmed hereditary angioedema attacks per 4 weeks (attack rate) from week 1 to week 25. Results A total of 90 patients received donidalorsen every 4 weeks (45 patients), donidalorsen every 8 weeks (23 patients), or placebo (22 patients). The least-squares mean time-normalized attack rate was 0.44 (95% CI, 0.27 to 0.73) in the 4-week group, 1.02 (95% CI, 0.65 to 1.59) in the 8-week group, and 2.26 (95% CI, 1.66 to 3.09) in the placebo group. The mean attack rate from week 1 to week 25 was 81% lower (95% CI, 65 to 89) in the 4-week group than in the placebo group (P<0.001) and 55% lower (95% CI, 22 to 74) in the 8-week group than in the placebo group (P=0.004); the median reduction in the attack rate from baseline was 90% in the 4-week group, 83% in the 8-week group, and 16% in the placebo group. The mean attack rate during weeks 5 to 25 was 87% lower (95% CI, 72 to 94) in the 4-week group than in the placebo group (P<0.001) and 60% lower (95% CI, 25 to 79) in the 8-week group than in the placebo group. Donidalorsen administered every 4 weeks resulted in an improvement in the least-squares mean total score for the change at week 25 on the Angioedema Quality-of-Life Questionnaire (scores range from 0 to 100, with a score of 100 indicating the worst possible quality of life) that was 18.6 points (95% CI, 9.5 to 27.7) better than that with placebo (P<0.001). The most common adverse events were erythema at the injection site, headache, and nasopharyngitis; 98% of adverse events were mild or moderate in severity. Conclusions Donidalorsen treatment reduced the hereditary angioedema attack rate, a finding that supports potential prophylactic use for hereditary angioedema. (Funded by Ionis Pharmaceuticals; OASIS-HAE ClinicalTrials.gov number, NCT05139810.)
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:001272081300004
WOS关键词	PREKALLIKREIN ; VALIDATION
WOS类目	Medicine, General & Internal
WOS研究方向	General & Internal Medicine
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/404978
推荐引用方式 GB/T 7714	Riedl, Marc A.,Tachdjian, Raffi,Lumry, William R.,et al. Efficacy and Safety of Donidalorsen for Hereditary Angioedema[J],2024,391(1):21-31.
APA	Riedl, Marc A..,Tachdjian, Raffi.,Lumry, William R..,Craig, Timothy.,Karakaya, Gul.,...&Cohn, Danny M..(2024).Efficacy and Safety of Donidalorsen for Hereditary Angioedema.NEW ENGLAND JOURNAL OF MEDICINE,391(1),21-31.
MLA	Riedl, Marc A.,et al."Efficacy and Safety of Donidalorsen for Hereditary Angioedema".NEW ENGLAND JOURNAL OF MEDICINE 391.1(2024):21-31.