Tocilizumab: An Interleukin-6 Receptor Inhibitor for the Treatment of Rheumatoid Arthritis
Tocilizumab: An Interleukin-6 Receptor Inhibitor for the Treatment of Rheumatoid Arthritis
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DOI：
10.1345/aph.1l268
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发表时间：
2008-11-01
影响因子：
2.9
通讯作者：
Plushner, Susyn L.
中科院分区：
文献类型：
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作者：
Plushner, Susyn L.
目的：综述靶向白细胞介素-6细胞因子受体的新型生物制剂托珠单抗的药理学、药代动力学、临床试验数据和安全性。资料来源：系统检索MEDLINE（1998- 2008年6月）和International Pharmaceutical Abstracts（1970- 2008年6月），确定已发表的临床试验和综述文章。关键检索词为托珠单抗、MRA、白细胞介素-6/受体、白细胞介素-6/免疫学和类风湿性关节炎。检索仅限于以英语发表的人类研究。对本次检索期间找到的文献中的参考文献进行了评价，以确定是否有其他相关引文。本文还回顾了国内和国际风湿病会议（美国风湿病学会和欧洲抗风湿联盟）和未发表的3期临床试验（使用www.clinicaltrials.gov）的摘要。研究选择和数据提取：所有描述托珠单抗药理学、药代动力学、疗效、安全性和不良反应的人体研究都包括在内。在大于4 mg/kg的剂量下，托珠单抗的使用导致临床结果的显著改善，包括美国流变学学院参数，其指示患者的改善和疾病缓解水平。当托珠单抗作为单药治疗或与甲氨蝶呤或其他改善疾病的抗风湿药物联合使用时，观察到改善。托珠单抗的最有效剂量似乎是8 mg/kg，这在关节损伤的放射学测量中显示出显著改善。最常见的不良反应包括肝功能检查结果异常，高脂血症，中性粒细胞减少症，感染，鼻咽炎，胃肠道的投诉，肌肉骨骼疾病，头痛，皮疹，瘙痒症。结论：托珠单抗是一个有前途的新的治疗类风湿关节炎。进一步的研究是必要的，以确认其放射学的好处，澄清其安全性，并确定其在类风湿关节炎治疗相对于目前的生物制剂。
OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trial data and safety profile of tocilizumab, a new biologic agent targeting the interleukin-6 cytokine receptor.DATA SOURCES: A systematic search of MEDLINE (1998-June 2008) and International Pharmaceutical Abstracts (1970-June 2008) was performed to identify published clinical trials and review articles. Key search terms were tocilizumab, MRA, interleukin-6/receptors, interleukin-6/immunology, and rheumatoid arthritis. The search was limited to studies in humans that were published in the English language. References from articles located during this search were evaluated for other relevant citations. Abstracts from national and international rheumatology meetings (American College of Rheumatology and European League Against Rheumatism) and from unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed.STUDY SELECTION AND DATA EXTRACTION: All available human studies describing the pharmacology, pharmacokinetics, efficacy, safety, and adverse effects of tocilizumab were included.DATA SYNTHESIS: At doses greater than 4 mg/kg, tocilizumab use has resulted in significant improvement in clinical outcomes, including the American College of Rheumatology parameters indicating a patient's level of improvements and disease remission. Improvements were noted when tocilizumab was used as monotherapy or in combination with methotrexate or other disease modifying antirheumatic drugs. The most effective dose of tocilizumab appears to be 8 mg/kg, which has shown significant improvements in radiographic measures of joint damage. The most common adverse effects have included abnormal results of liver function tests, hyperlipidemia, neutropenia, infections, nasopharyngitis, gastrointesitinal complaints, musculoskeletal disorders, headache, rash, and pruritus.CONCLUSIONS: Tocilizumab represents a promising new treatment for rheumatoid arthritis. Additional research is warranted to confirm its radiographic benefits clarify its safely profile, and identify its place in rheumatoid arthritis treatment relative to current biologic agents.