比较三种新型生物制剂治疗中重度活动性类风湿关节炎的疗效与安全性_赵征

比较三种新型生物制剂治疗中重度活动性类风湿关节炎的疗效与安全性

赵　征，朱　剑，张江林，张亚美，黄　烽，邓小虎（解放军总医院风湿科，北京 100853）

[摘要]　目的：观察利妥昔单抗、托珠单抗及阿达木单抗联合慢作用抗风湿药物（DMARDs）治疗中重度活动性类风湿关节炎24周后的疗效和安全性。方法：共入组87例DAS28 > 3.2的活动性类风湿关节炎患者，给予利妥昔单抗或托珠单抗或阿达木单抗同时联合DMARDs，或仅用DMARDs药物治疗，主要疗效指标为达到ACR20的患者比例，次要疗效指标为达到ACR50、ACR70的比例及DAS28-CRP的改善情况。结果：在24周时，利妥昔单抗、托珠单抗及阿达木单抗达到ACR20的比例分别为66.67%、94.44%和73.08%，而单用DMARDs组则为53.57%，同时各治疗组患者DAS28-CRP亦较基线及仅用DMARDs组显著下降，且托珠单抗及阿达木单抗组优于利妥昔单抗组。最常见的不良事件为上呼吸道感染，其次是淋巴细胞下降及肝功能异常。结论：利妥昔单抗、托珠单抗及阿达木单抗对类风湿关节炎均具有显著的疗效和良好的安全性，阿达木单抗及托珠单抗的疗效优于利妥昔单抗。

[关键词]　生物制剂；类风湿关节炎；疗效；安全性；药品不良反应

[中图分类号]　R971+.1；R969.4 [文献标识码]　A [文章编号]　1672 – 8157(2014)03 – 0134 – 05

Effi cacy and safety of three new biologics in the treatment of moderate to severe rheumatoid arthritis

ZHAO Zheng, ZHU Jian, ZHANG Jiang-lin, ZHANG Ya-mei, HUANG Feng, DENG Xiao-hu(Department of Rheumatology, PLA General Hospital, Beijing 100853, China)

[ABSTRACT]　Objective: To observe the efficacy and safety of rituximab, tocilizumab and adalimumab combined with disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methods: A total of 87 RA patients with a 28-joint Disease Activity Score (DAS28) >3.2 were randomly given rituximab, tocilizumab, adalimumab combined with DMARDs respectively or DMARDs alone for 24 weeks. The primary end point was the proportion of patients achieving American College of Rheumatology criteria for 20% improvement (ACR20). The secondary end points included the proportion of patients achieving ACR50, ACR70, improvement of DAS28, C-reactive protein (CRP) and Health Assessment Questionnaire (HAQ). Safety was assessed by adverse event documentation. Results: At the end of the 24th week, 82 patients completed the treatment. The proportion of patients achieving ACR20 treated by rituximab + DMARDs, tocilizumab + DMARDs, adalimumab + DMARDs, DMARDs alone was 66.67%, 94.44%, 73.08% and 53.57% respectively. Results for other secondary efficacy endpoints showed that these three new biologics could provide substantial benefi ts to patients with RA by reducing clinical signs, HAQ and DAS28. Effi cacy of tocilizumab and adalimumab were better than rituximab. Most treatment-related adverse events were mild to moderate. The most common adverse event was upper respiratory tract infection. Lymphocytes decreased and abnormal liver function was next. No serious infections were observed. Conclusion: These three new biologics have signifi cant effi cacy and good safety towards RA patients. The effi cacy of tocilizumab and adalimumab are better than rituximab.

[KEY WORDS]　Biologics; Rheumatoid arthritis; Effi cacy; Safety; Adverse drug reaction

类风湿关节炎（rheumatoid arthritis，RA）是一种常见的以慢性多关节滑膜炎为主要临床表现的自身免疫性疾病，发病率高，致残性强，以对称性、进行性和破坏性关节病变为主要特征，严重者可出现关节畸形。随着生物制剂的应用（包括抗肿瘤坏死因子-α[1-2]，IL-1受体抑制剂[3]，人鼠崁合的抗CD20单克隆抗体[4]，以及IL-6受体单抗），治疗炎性关节炎发生了一系列的变化。

本研究选择了3种不同作用机制治疗类风湿关节炎的生物制剂，包括利妥昔单抗、托珠单抗及阿达木单抗。利妥昔单抗是一种新型的基因工程技术制备

[通信作者]　邓小虎，男，副主任医师，主要从事风湿病方面的工作。E-mail：dengxh1970@

[作者简介]　赵征，女，主治医师，主要从事风湿病方面的工作。E-mail：sisyzz1979@

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