阿达木单抗治疗类风湿关节炎的疗效和安全性

Efficacy and safety of adalimumab in patients with rheumatoid arthritis

目的:评价肿瘤坏死因子α拮抗剂阿达木单抗短期治疗类风湿关节炎(RA)的临床疗效及安全性,同时检测治疗前后类风湿因子(RF)和抗环瓜氨酸肽抗体(抗CCP抗体)滴度的变化,为RA疗效评估寻找新的指标。方法:随机双盲平行试验,纳入40例活动性RA患者,按2∶2∶1的比例被随机分配到试验组或对照组,试验组分为80 mg阿达木单抗+甲氨喋呤(MTX)、40 mg阿达木单抗+MTX两组,对照组为安慰剂+MTX。受试者隔周接受皮下注射阿达木单抗或同等体积的安慰剂,并在试验第0,2,4,8,12周随访,评价疗效及不良事件收集。疗效采用ACR核心标准评定。次要疗效指标包括压痛和肿胀关节数、晨僵时间、疼痛视觉模拟评分(VAS评分)、健康评估问卷(HAQ)和CRP。基线时及12周治疗结束后检测RF、抗CCP抗体。结果:试验组32例,对照组8例。12周后试验组患者ACR20、ACR50和ACR70缓解的比例都显著高于对照组(P<0.01);试验组患者关节触痛数、关节肿胀数、晨僵持续时间、疼痛VAS评分及健康状况问卷(HAQ)、CRP等次要疗效指标均较基线时水平明显降低(P<0.05);试验组RF血清滴度和抗CCP抗体均较基线时水平显著降低(P<0.05),而对照组没有观察到RF和CCP抗体滴度的显著改变。总体上来说阿达木单抗不良反应轻微,耐受性较好。结论:阿达木单抗+MTX治疗RA的疗效明显优于单用MTX组,能迅速改善各项症状、体征和实验室炎性指标。RF和抗CCP抗体滴度的检测对监测TNF-α拮抗剂治疗的RA患者临床进程及疗效是有用的指标。

Objective： To evaluate the efficacy and safety of human monoclonal anti-TNF-α antibody（adalimumab） in patients with rheumatoid arthritis（RA）,and to analyze the relationship between efficacy and the titers of rheumatoid factor（RF） and anti-cyclic citrullinated peptide（anti-CCP） autoantibodies.Methods： In a double-blind,placebo-controlled prospective study,40 patients with active RA were enrolled and randomized to 3 groups.They were treated with 40 mg（n=16） or 80 mg adalimumab（n=16） in addition to a background treatment（stable doses of methotrexate）,or with placebo＋background treatment（n=8）.Symptom improvements and adverse reactions were assessed at weeks 0,2,4,8 and 12.Serum RF and anti-CCP autoantibodies were detected at baseline and at 12 weeks of follow-up.Results： The proportion of achieving American College of Rheumatology（ACR） 20,50,and 70 response criteria were significant higher in adalimumab groups than in placebo group（P0.01）.Tender joint count,swollen joint count,duration of morning stiffness,VAS score,HAQ and CRP were significantly decreased 12 weeks after adalimumab treatment（P0.05）.Adalimumab induced a significant decrease in serum levels of RF and anti-CCP（P0.05）,and the decrease in antibody titers was not seen in placebo group.The titers correlated with the clinical response to the therapy.Adalimumab was well-tolerated;adverse effects were little and light.Conclusion： Treatment with adalimumab plus methotrexate is more effective than methotrexate alone in active RA patients;the onset of effect is rapid.The titers of RF and anti-CCP autoantibodies may be potentially useful indicators to assess the effect of anti-TNF-α treatment in RA patients.