Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation.
Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation.
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DOI：
10.1136/bmjno-2020-000114
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发表时间：
2021
影响因子：
2.7
通讯作者：
Cooke DL
中科院分区：
文献类型：
--
作者：
Muster R;Ko N;Smith W;Su H;Dickey MA;Nelson J;McCulloch CE;Sneed PK;Clarke JL;Saloner DA;Eisenmenger L;Kim H;Cooke DL
脑动静脉畸形（bAVM）相对罕见，尽管其继发性颅内出血（ICH）的可能性使其诊断和管理对社区至关重要。目前，侵入性治疗（手术切除、立体定向放射外科和血管内栓塞）是唯一能够降低ICH风险的干预措施。尽管越来越多的动物和人类证据支持贝伐珠单抗在缩小AVM尺寸方面的作用，但尚无针对bAVM的指定药物治疗。在这项单组初步研究中，2例大型bAVM患者（被多学科团队认为不可切除）接受贝伐珠单抗5 mg/kg，每2周一次，持续12周。由于外部资金的限制，未能达到10名参与者的预期样本量。主要结局指标为26周和52周时bAVM体积较基线的变化。贝伐珠单抗治疗后26或52周，未观察到bAVM体积变化。在52周研究期间未观察到具有临床意义的不良事件。未观察到ICH事件。血清血管内皮生长因子水平在26周时降低，并在52周时恢复至基线水平。这项初步研究是第一个测试贝伐珠单抗治疗bAVM患者的研究。贝伐珠单抗治疗在2例受试者中耐受良好。在52周研究期间未观察到影像学变化。随后的大型临床试验是为了评估剂量依赖性疗效和罕见的药物不良反应。试验注册号：NCT 02314377。
Brain arteriovenous malformations (bAVMs) are relatively rare, although their potential for secondary intracranial haemorrhage (ICH) makes their diagnosis and management essential to the community. Currently, invasive therapies (surgical resection, stereotactic radiosurgery and endovascular embolisation) are the only interventions that offer a reduction in ICH risk. There is no designated medical therapy for bAVM, although there is growing animal and human evidence supporting a role for bevacizumab to reduce the size of AVMs. In this single-arm pilot study, two patients with large bAVMs (deemed unresectable by an interdisciplinary team) received bevacizumab 5 mg/kg every 2 weeks for 12 weeks. Due to limitations of external funding, the intended sample size of 10 participants was not reached. Primary outcome measure was change in bAVM volume from baseline at 26 and 52 weeks. No change in bAVM volume was observed 26 or 52 weeks after bevacizumab treatment. No clinically important adverse events were observed during the 52-week study period. There were no observed instances of ICH. Sera vascular endothelial growth factor levels were reduced at 26 weeks and returned to baseline at 52 weeks. This pilot study is the first to test bevacizumab for patients with bAVMs. Bevacizumab therapy was well tolerated in both subjects. No radiographic changes were observed over the 52-week study period. Subsequent larger clinical trials are in order to assess for dose-dependent efficacy and rarer adverse drug effects. Trial registration number: NCT02314377.
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影响因子：
2.6
作者：
Hashimoto T;Matsumoto MM;Li JF;Lawton MT;Young WL;University of California, San Francisco, BAVM Study Group
通讯作者：
University of California, San Francisco, BAVM Study Group
影响因子：
4.1
作者：
BROWN, RD;WIEBERS, DO;MACIUNAS, RJ
通讯作者：
MACIUNAS, RJ
影响因子：
4.8
作者：
Hashimoto, T;Emala, CW;Young, WL
通讯作者：
Young, WL
影响因子：
3.9
作者：
Deibert, Christopher P.;Ahluwalia, Manmeet S.;Kondziolka, Douglas
通讯作者：
Kondziolka, Douglas
影响因子：
48
作者：
Mohr, Jay P.;Overbey, Jessica R.;Moskowitz, Alan J.
通讯作者：
Moskowitz, Alan J.