泊马度胺治疗遗传性出血性毛细血管扩张症鼻出血。
Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia.
机构信息
From Massachusetts General Hospital, Boston (H.A.-S.); University of North Carolina, Chapel Hill (R.S.K.), and RTI International, Research Triangle Park (D.M., L.B., B.A.C., S.M.T.) - both in North Carolina; Mayo Clinic, Rochester, MN (V.N.I.); University of Pennsylvania, Philadelphia (A.M.P.); Medical College of Wisconsin, Milwaukee (J.E.D.); Johns Hopkins University, Baltimore (C.R.W.), and CureHHT, Monkton (M.C.) - both in Maryland; University of Utah, Salt Lake City (K.J.W.); University of California, San Francisco, San Francisco (M.B.C.); University of Florida, Gainesville (M.S.Z.); University of California, San Diego, La Jolla (J.Y.Z.); and Taussig Cancer Center and Lerner Research Institute (K.R.M.), Cleveland Clinic (J.P., L.W., K.R.M.), Cleveland.
出版信息
N Engl J Med. 2024 Sep 19;391(11):1015-1027. doi: 10.1056/NEJMoa2312749.
BACKGROUND
Hereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life.
METHODS
We conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations).
RESULTS
The trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was -0.94 points (95% confidence interval [CI], -1.57 to -0.31; P = 0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was -1.4 points (95% CI, -2.6 to -0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash.
CONCLUSIONS
Among patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified. (Funded by the National Heart, Lung, and Blood Institute; PATH-HHT Clinicaltrials.gov number, NCT03910244).
背景
遗传性出血性毛细血管扩张症（HHT）的特征是广泛的毛细血管扩张和动静脉畸形。主要临床表现为导致缺铁性贫血和降低健康相关生活质量的鼻出血。
方法
我们进行了一项随机、安慰剂对照试验，以评估泊马度胺治疗 HHT 的安全性和疗效。我们以 2:1 的比例随机分配患者，每天接受泊马度胺 4 毫克或匹配的安慰剂治疗 24 周。主要结局是从基线到第 24 周时，Epistaxis Severity Score（HHT 的一种经过验证的出血评分；范围为 0 至 10，得分越高表示出血越严重）的变化。降低 0.71 分或更多被认为具有临床意义。一个关键的次要结局是 HHT 特异性生活质量评分（范围为 0 至 16，得分越高表示限制越多）。
结果
在计划的中期分析达到疗效的预设阈值后，试验于 2023 年 6 月停止入组。共有 144 名患者接受了随机分组；95 名患者接受泊马度胺治疗，49 名患者接受安慰剂治疗。基线时平均（±SD）Epistaxis Severity Score 为 5.0±1.5，表明中重度鼻出血。24 周时，泊马度胺组与安慰剂组在 Epistaxis Severity Score 从基线变化的平均差异为-0.94 分（95%置信区间，-1.57 至-0.31；P=0.004）。两组间 HHT 特异性生活质量评分变化的平均差异为-1.4 分（95%置信区间，-2.6 至-0.3）。泊马度胺组比安慰剂组更常见的不良反应包括中性粒细胞减少症、便秘和皮疹。
结论
在 HHT 患者中，泊马度胺治疗可显著、具有临床意义地降低鼻出血严重程度。未发现意外的安全信号。（由美国国立心肺血液研究所资助；PATH-HHT Clinicaltrials.gov 编号，NCT03910244）。
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