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在类风湿性关节炎患者以及先前使用肿瘤坏死因子α阻滞剂治疗失败的患者中,利妥昔单抗比二线抗肿瘤坏死因子治疗更有效。

Rituximab is more effective than second anti-TNF therapy in rheumatoid arthritis patients and previous TNFα blocker failure.

作者信息

Kekow Joern, Mueller-Ladner Ulf, Schulze-Koops Hendrik

机构信息

Clinic of Rheumatology and Orthopedics, Otto-von-Guericke University of Magdeburg, Vogelsang-Gommern.

出版信息

Biologics. 2012;6:191-9. doi: 10.2147/BTT.S32244. Epub 2012 Jul 2.

Abstract

PURPOSE

To assess the efficacy of one course of rituximab (two 1-g doses) compared to an alternative tumor necrosis factor-α (TNFα) blocker in rheumatoid arthritis patients who had experienced one previous TNFα blocker failure (eg, etanercept, adalimumab, or infliximab).

PATIENTS AND METHODS

The efficacy of both treatments was studied in this retrospective, multicenter, noninterventional cohort study with 196 patients. All patients had active rheumatoid arthritis defined by a Disease Activity Score-28 of ≥3.2 despite having TNFα blocker therapy, and were followed over 6.6 months on average after switching to rituximab versus a second TNFα blocker (ie, switching to etanercept, adalimumab, or infliximab) at baseline.

RESULTS

At baseline, both cohorts showed similar demographic and disease-related characteristics (including Disease Activity Score-28). At the end of observation, mean Disease Activity Score-28 was significantly lower after treatment with rituximab than with a second TNFα blocker (-1.64 [95% confidence interval: -1.92; -1.36] versus -1.19 [95% confidence interval: -1.42; -0.96], P = 0.013). This difference between the two groups was even more pronounced when patients were seropositive for rheumatoid factor (-1.66 versus -1.17, P = 0.018) and anti-cyclic citrullinated peptide antibodies (-1.75 versus -1.06, P = 0.002). More rituximab-treated patients achieved good European League Against Rheumatism response than TNFα blocker-treated patients (30% versus 15%), and less patients were nonresponders (22% versus 35%) according to European League Against Rheumatism criteria (P = 0.022, chi-squared test).

CONCLUSION

Treatment with rituximab was more effective than a second TNFα blocker therapy in rheumatoid arthritis patients after failure of the first TNFα blocker. It was found that anti-cyclic citrullinated peptide antibodies may be a useful predictive biomarker for response to rituximab in patients with TNFα blocker treatment failure.

摘要

目的

评估在既往一种肿瘤坏死因子-α(TNFα)阻滞剂治疗失败(如依那西普、阿达木单抗或英夫利昔单抗)的类风湿关节炎患者中,一个疗程的利妥昔单抗(两个1克剂量)与另一种TNFα阻滞剂相比的疗效。

患者与方法

在这项回顾性、多中心、非干预性队列研究中,对196例患者研究了两种治疗方法的疗效。所有患者尽管接受了TNFα阻滞剂治疗,但疾病活动评分-28(DAS28)≥3.2,仍患有活动性类风湿关节炎,且在基线时转用利妥昔单抗与第二种TNFα阻滞剂(即转用依那西普、阿达木单抗或英夫利昔单抗)后平均随访6.6个月。

结果

在基线时,两个队列显示出相似的人口统计学和疾病相关特征(包括DAS28)。在观察结束时,利妥昔单抗治疗后的平均DAS28显著低于第二种TNFα阻滞剂(-1.64[95%置信区间:-1.92;-1.36]对-1.19[95%置信区间:-1.42;-0.96],P=0.013)。当患者类风湿因子血清学阳性(-1.66对-1.17,P=0.018)和抗环瓜氨酸肽抗体阳性(-1.75对-1.06,P=0.002)时,两组之间的差异更为明显。根据欧洲抗风湿病联盟标准,接受利妥昔单抗治疗的患者达到良好欧洲抗风湿病联盟反应的比例高于接受TNFα阻滞剂治疗的患者(30%对15%),无反应者较少(22%对35%)(P=0.022,卡方检验)。

结论

在第一种TNFα阻滞剂治疗失败的类风湿关节炎患者中,利妥昔单抗治疗比第二种TNFα阻滞剂治疗更有效。发现抗环瓜氨酸肽抗体可能是TNFα阻滞剂治疗失败患者对利妥昔单抗反应的有用预测生物标志物。

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