Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease
Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease
复制标题
DOI：
10.1182/blood-2004-12-4602
复制
发表时间：
2005-10-15
期刊：
影响因子：
20.3
通讯作者：
Kishimoto, T
中科院分区：
文献类型：
--
作者：
Nishimoto, N;Kanakura, Y;Kishimoto, T
多中心Castleman病（MCD）是一种以全身淋巴结肿大和全身炎症症状为特征的非典型淋巴组织增生性疾病。白细胞介素-6的过度生产失调是导致临床异常的原因。本多中心前瞻性研究旨在评价人源化抗人白细胞介素-6（IL-6）受体单克隆抗体（MRA）在MCD患者中的安全性和有效性。我们在这里报告的结果的前60周的研究招募28名患者。初始给药期包括8 mg/kg MRA输注8次，每两周一次。在16周后的扩展阶段，允许对每例患者的剂量和治疗间隔进行调整。在16周内，MRA治疗始终减轻淋巴结肿大和所有炎症参数。血红蛋白、白蛋白、总胆固醇水平、高密度脂蛋白胆固醇值和体重指数均显著升高。此外，疲劳减轻。慢性炎症症状在60周内得到成功控制。在8例（28.6%）患者中，MRA剂量降低或治疗间隔延长，但未发生恶化。15例患者中有11例（73.3%）在研究入组前接受了口服皮质类固醇，在减少皮质类固醇剂量后表现良好。大多数不良事件的严重程度为轻度至中度。MRA耐受性良好，显著减轻MCD患者的慢性炎症症状和消瘦。
Multicentric Castleman disease (MCD) is an atypical lymphoproliferative disorder characterized by systemic lymphadenopathy and constitutional inflammatory symptoms. Dysregulated overproduction of interleukin-6 is responsible for the clinical abnormalities. This multicenter prospective study was undertaken to evaluate the safety and efficacy of a humanized antihuman interleukin-6 (IL-6) receptor monoclonal antibody (MRA) in patients with MCD. We report here results of the first 60 weeks of the study enrolling 28 patients. The initial dosing period consisted of 8 infusions of 8 mg/kg MRA administered biweekly. Adjustments in the dose and treatment interval were allowed for each patient in an extension phase after 16 weeks. Within 16 weeks, treatment with MRA consistently alleviated lymphadenopathy and all the inflammatory parameters. Hemoglobin, albumin, and total cholesterol levels, high-density lipoprotein cholesterol values, and body mass index all increased significantly. In addition, fatigue diminished. Chronic inflammatory symptoms were successfully managed over 60 weeks. In 8 (28.6%) patients, the MRA dose was decreased or the treatment interval was extended without exacerbation. Eleven (73.3%) of 15 patients who had received oral corticosteroids before study entry were able to do well on a reduced corticosteroid dose. Most adverse events were mild to moderate in severity. MRA was tolerated well and significantly alleviated chronic inflammatory symptoms and wasting in patients with MCD.