本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2402478

摘要内容如下：

背景

遗传性血管性水肿是一种罕见的疾病，其特征是由激肽释放酶-激肽失调引起的发作性、可能危及生命的肿胀。长期预防可以稳定这一系统。Donidalorsen是一种反义寡核苷酸，可特异性降低前激肽释放酶的表达。

方法

在这项3期、双盲、随机试验中，我们将遗传性血管性水肿患者分为两组，每4周或8周接受一次多尼达洛森（皮下注射80 mg）或安慰剂。主要终点是从第1周到第25周每4周经研究者证实的遗传性血管性水肿发作的时间标准化次数（发作率）。

结果

共有90名患者接受每4周一次的多尼达洛森治疗（45名患者）、每8周一次的多尼达洛森治疗（23名患者）或安慰剂治疗（22名患者）。4周组的最小二乘平均时间标准化发作率为0.44（95%CI，0.27至0.73），8周组为1.02（95%CI，0.65至1.59），安慰剂组为2.26（95%CI，1.66至3.09）。从第1周到第25周，4周组的平均发病率比安慰剂组低81%（95%CI，65-89）（p<0.001），8周组比安慰剂组低55%（95%CI，22-74）（p=0.004）；与基线相比，4周组、8周组和安慰剂组的平均发病率分别降低了90%、83%和16%。在第5周至第25周期间，4周组的平均发病率比安慰剂组低87%（95%CI，72至94）（P<0.001），8周组比安慰剂组低60%（95%CI，25至79）。每4周给予多尼达洛森，导致第25周血管性水肿生活质量问卷（得分范围为0至100，得分为100表示生活质量可能最差）的最小二乘平均总分改善，比安慰剂组高18.6分（95%CI为9.5至27.7）（P<0.001）。最常见的不良反应是注射部位红斑、头痛和鼻咽炎。98%的不良事件为轻度或中度。

结论

多尼达洛森治疗降低了遗传性血管性水肿的发病率，这一发现支持了对遗传性血管性水肿的潜在预防性应用。（由Ionis Pharmaceuticals资助；Oasis-Hae ClinicalTrials.gov编号，NCT05139810。）

英文原文如下：

Abstracts

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.).

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