重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗类风湿关节炎双盲随机多中心对照临床研究

Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor-Fc fusion protein:a multicenter,randomized,double blind,controlled trial

目的研究注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白[rhTNFR:Fc,益赛普,(etanercept)]对活动性类风湿关节炎(RA)患者的疗效及安全性。方法238例患者随机分为试验组和对照组。试验组每周1次口服空白模拟甲氨蝶呤(MTX),同时接受rhTNFR:Fc皮下注射治疗,每周2次,每次25mg;对照组每周1次口服定量MTX(每周7.5mg起,8周内增至15mg),同时每周2次皮下注射空白模拟rhTNFR:Fc。疗程24周。疗效评价采用美国风湿病学会(ACR)疗效评定标准。结果治疗2周后,rhTNFR:Fc组ACR20有效率为35.59%,MTX组为22.50%,组间比较差异有统计学意义(P<0.05)。治疗8周后,rhTNFR:Fc组和MTX组的ACR20、ACR50和ACR70组间比较差异均有统计学意义(P<0.05)。治疗12周后,rhTNFR:Fc组ACR20有效率为66.10%,MTX组是51.67%,两组间比较差异有统计学意义(P<0.05)。治疗24周后,rhTNFR:Fc组ACR20有效率为75.42%,且ACR70有效率优于MTX组(P<0.05),显示rhTNFR:Fc疗效强于MTX。两组药物之间总的不良反应发生率差异无统计学意义。结论rhTNFR:Fc用于治疗中、重度RA具有良好的安全性和显著的疗效;在前12周治疗期间,rhTNFR:Fc较MTX起效快、效果更明显。

Objective To compare the efficacy and safety of recombinant human tumor necrosis factor-Fe （rhTNFR：Fe） and methotrexate （MTX） in patients with active rheumatoid arthritis. Methods Two hundred and thirty-eight patients with rheumatoid arthritis were treated with either twice-weekly subcutaneous rhTNFR：Fc （25 mg） or weekly oral MTX （mean, 15 mg per week） for 24 weeks. Clinical assessments using the American College of Rheumatology （ACR） criteria for improvement were performed at baseline and at 2, 4, 6, 8, 12, 16, 20 and 24 weeks, and serious adverse events were monitored throughout the study. Results As compared with patients who received MTX, patients who received rhTNFR：Fc had a more rapid ACR20 improvement in disease activity during the first two weeks （P〈0.05）. Patients received rhTNFR：Fc had a more rapid improvement, with significant more patients having ACR20, ACR50, ACR70 improvement in disease activity during the eight weeks （P〈0.05）. At the end of 12 weeks treatment, patients with rhTNFR：Fc also had significant improvement at ACR20 （P〈0.05） compared to the baseline. Compared with oral MTX, patients received rhTNFR：Fc also had significant improvement at ACR20 and ACR70 at the end of 24 weeks treatment （P〈0.05）. There was no significant difference between the two groups in adverse effects. Conclusions rhTNFR：Fc has significant efficacy and safety in patients with rheumatoid arthritis. Compared with oral MTX, intravenous rhTNFR：Fc acts more rapidly in decreasing symptoms and slowing joint damage.