托珠单抗治疗难治性类风湿关节炎的临床观察

Clinical Observation on Tocilizumab in Treating Resistant Rheumatoid Arthritis

目的 探讨托珠单抗治疗活动性难治性类风湿关节炎（RRA）的短期临床疗效及安全性。方法 选择 2013 年 10 月－ 2014 年 10 月使用托珠单抗治疗的 RRA 患者 40 例，给予托珠单抗 8 mg/kg，每 4 周输注 1 次，合并用药维持剂量不变。在基线水平，第 1、4、12、16、24 周和停用托珠单抗 4、8 周时分别评价临床和实验室指标。结果 在随访的各时间点患者RRA的各项指标均有一定改善，且随治疗时间的延长，各项指标呈进行性下降趋势。第 1 周时疼痛评分、红细胞沉降率、C 反应蛋白、28 个关节疾病活动度评分（DAS28）和健康评估问卷（HAQ）就有明显下降（P ＜ 0.05），第 12 周时所有患者的炎症指标已降至正常范围，63%（22/35）的患者达到美国风湿病学会制定的疾病活动度缓解 20%，29%（10/35）的患者达到美国风湿病学会制定的疾病活动度缓解 50%。第 24 周时 12例患者达到低疾病活动度（DAS28 评分≤ 3.2 分）及 ACR50。HAQ 评分在治疗第 24 周时最低（3.1±1.6）分，与基线时的（20.2±6.7）分相比差异有统计 学意义（P ＜ 0.01）。停用托珠单抗 4 周时，所有指标回升不明显。停药 8 周时，除了肿胀关节数、C 反应蛋白、DAS28 和 HAQ 无明显反弹外，其余指标均较停药 4 周时有明显增加（P ＜ 0.01）。不良反应主要为肝功能异常和血脂升高，其次为白细胞减少。仅 1 例患者因不良反应停药。结论 托珠单抗对RRA 的疗效确切、快速，安全性良好，停药后其疗效仍能维持 4 ～ 8 周。

Objective To study the short-term efficacy and safety of tocilizumab in treating patients with active and resistant rheumatoid arthritis （RRA）. Methods Forty patients with RRA treated with tocilizumab between October 2013 and October 2014 were included in our study. The combined drug treatment was continued with the addition of tocilizumab 8 mg/kg per four weeks. The clinical responses and laboratory parameters were evaluated at the baseline, week 1, 4, 12, 16 and 24, and week 4 and 8 of tocilizumab withdrawal. Results Tocilizumab was effective for several clinical lesions and laboratorial parameters at all time points. With the extension of treatment, the effect was better. At week 1, the visual analogue scale score of pain by patients, erythrocyte sedimentation rate, C-reactive protein （CRP）, disease activity score 28 （DAS28） and health assessment questionnaire （HAQ） results decreased significantly （P 〈 0.05）. At week 12, the inflammatory biomarkers of all patients were normal, and 62.9% （22/35） of the patients achieved American College of Rheumatology （ACR）20, and 28.6% （10/35） of the patients achieved ACR50. At week 24, twelve patients achieved ACR50 and low activity （DAS28 score ≤ 3.2）, and the score of HAQ was minimum （3.1±1.6）. The score of HAQ was significantly different between week 24 and the baseline （20.2±6.7） （P 〈 0.01）. All parameters were not significantly changed at week 4 of tocilizumab withdrawal compared with those before the withdrawal. Most parameters increased significantly at week 8 of tocilizumab withdrawal compared with week 4 of withdrawal （P 〈 0.01） except for swollen joints, CRP, DAS28 and HAQ. The main adverse reactions were abnormal hepatic function and dyslipidemia followed by leukopenia. Only one patient stopped treatment because of adverse reaction. Conclusions Tocilizumab has rapid efficacy onset and goodsafety. After tocilizumab withdrawal, the efficacy can be maintained for 4 to 8 weeks.