Etanercept治疗未分化脊柱关节病患者的临床疗效和安全性初步研究

Study on the efficacy and safety of etanercept in patients with uSpA

目的评价etanercept治疗未分化脊柱关节病（uSpA）患者的临床疗效以及安全性，并随访观察停药后患者复发的情况。方法研究共纳入30例活动性uSpA患者，前6周为随机双盲、安慰剂对照试验，后6周为开放性试验，受试者接受每周皮下注射etanercept或安慰剂2次，每次25mg。主要评价指标为第6和12周达到As疗效评价标准（ASAS）20改善的比例，次要标准包括第6和12周达到ASAS50及ASAS70改善的比例,以及ASAS评价系统各单项指标的变化。用药结束后对患者进行定期随访，观察其复发时间。结果第6周安慰剂组所有指标较基线均无显著改善，而etanercept组除C反应蛋白（cRP）外其他指标均显著改善；两组间达到ASAS70改善的患者比例分别为33．3％和0，两组比较差异有统计学意义（P〈0．05）。第12周两组间各个指标比较P〉0．05。21例在12周达到ASAS20改善者在试验结束后随访满12个月，总计有11例（52．4％）患者复发，平均复发时间（5±4）个月；其中etanercept组7例，安慰剂组4例（两组比较P〉0.05）。不良反应均为轻至中度，主要有注射部位皮肤反应、上呼吸道感染、转氨酶升高等。结论Etanercept治疗uSpA患者6或12周均能明显改善症状，且部分患者停药后能获得大于1年的良好控制症状效果，但能否真正控制病情进展和如何延续疗效尚待更多的临床研究和验证。

Objective To determine the clinical efficacy and safety of etanercept in patients with uSpA. Method A 3 months, double-blind, placebo-controlled trial was conducted. Patients with active uSpA （n=30） were treated with either etanercept （n=15） or placebo （n=15） subcutaneously injection twice weekly for 6 weeks and followed by additional etanlercept injection for 6 weeks. The primary outcome measures were the percentage of patients achieving the ASAS20 response at the sixth week and the twelfth week. Other outcome measures included the percentage of patients achieving the ASAS50 or ASAS70 response at the sixth week and twelfth week and the change of single parameter in the ASAS core sets. Patients were followed up until relapse or 1 year. Results At the 6th week, all parameters except BASDAI had no difference between the treatment and placebo group compared with the baseline. In the etanereept group, all parameters except CRP decreased significantly. But there was no difference between the two groups in all parameters. The percentage of patients achieving ASAS70 response was significantly different, but not in the percentage of patients achieving ASAS20 and ASAS50. After treated for 12 weeks, all parameters except CRP decreased significantly in both groups compared to the baseline. But no significant difference was found between the two groups. No significant difference could be detected in the percentage of patients achieving ASAS20/ASAS50/ASAS70 between the two groups. Among the 21 patients who achieved ASAS20 response, 9 relapsed during the 1 year follow-up period. There was no significant difference between the two groups in the number of relapse. The adverse events included injection site eaction, upper respiratory tract infection and elevated liver transaminase. Conclusion Etanereept can relieve symptoms in uSpA patients. And some patients can get long-term relieve. However, whether it can delay the disease progression should be studied further.