注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白剂量递减方案治疗强直性脊柱炎的临床疗效观察

Comparing tapering strategy to standard dosing regimen of recombinant human tumor necrosis factor receptor-Ig fusion protein for injection in patients with ankylosing spondylitis in low disease activity

目的比较依那西普生物类似药注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（强克）治疗AS时，患者达低疾病活动度后剂量递减方案与标准剂量维持方案在AS中的疗效、复发率、安全性及相关花费等结果。方法研究纳入来自上海交通大学医学院附属仁济医院风湿科门诊或住院的活动性AS患者，接受标准剂量注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗达低疾病活动状态后，分别进入剂量递减组或标准剂量组进行治疗。剂量递减方案由主治医生根据患者疾病活动情况个体化制定。采用倾向指数分析对患者进行基线信息匹配，包括年龄、性别、病程、BASFI和药物使用剂量等。记录患者基线（TO）、达低疾病活动度开始分组前（T1）及随后每2个月时的BASDAI、BASFI、CRP水平等疾病相关指标，并定期监测肝功能、肾功能等常规指标，记录可能发生的不良事件。采用t检验、Mann—Whitney U检验、χ2检验进行分析。结果研究共纳入127例As患者，达低疾病活动状态后72例接受依那西普生物类似药剂量递减方案治疗，55例接受依那西普生物类似药标准剂量治疗。随访时间为1年，各访视时间点2组患者的BASDAI评分（所有访视点2组P值均〉0．05）、BASFI改变（2．1±4．6和2．3±3-3，t=1．78，P=0．69）、CRP水平类似，差异无统计学意义；但是剂量递减组费用显著低于剂量标准组[（47328±5695）元和（84864±569）元，年，t=0．015，P〈0．05]。随访期间共有33例（26．5％）患者经历了至少1次复发，其中剂量递减组为21／72例（29％），标准剂量组为12／55例（22％），2组差异无统计学意义（r=0．88，P=0．347）。多数患者（70％）在后来的随访期间重新恢复至低疾病活动状态。2组患者不良反应发生率差异无统计学意义。结论注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗As达低疾病活动状态后，剂量递减方案与标准剂量方案1年的临床疗效及复发率差异无统计学意义，但相关药物花费更低。

Objective To compare the effectiveness, safety and costs of standard versus individually tailored reduced doses of recombinant human tumor necrosis factor receptor-Ig fusion protein for injection （rhTNFR：Fc） in patients with ankylosing spondylitis （AS） after achieving low disease activity. Methods This was a single center prospective observational study performed within Renji Hospital. The etanercept biosimiliar （Qiangke） tapering strategy was chosen by treating physicians, without pre-specified protocol. We used propensity score （PS） methodology to identify 2 cohorts of patients matched for relevant baseline characteristics including age, gender, baseline activity, baseline function, disease duration, duration Of anti-tumor necrosis factor （TNF） therapy. Multiple clinical indexes including Bath ankylosing spondyliti diseases activity index （BASDAI） and Bath ankylosing spondylitis functional index （BASFI）,.C reactive protein （CRP） at baseline and every follow up visits and costs of rhTNFR：Fc drugs were compared between both PS-matched cohorts. T test, Mann-Whitney U test, chi-square test were used for statistical analysis. Results One hundred and twentyseven consecutive AS patients were included who were treated with either reduced （n=72） or standard （n=55） doses of TNF inhibitors. The mean change per 1 year in BASFI, as well as BASDAI and CRP of every visit was not different between both groups, but the cost for anti-TNF drugs was substantially lower in the reduced dosing group [（47 328±5 695） Y/year vs （84 864±569） ￥/year, t=0.015, P〈0.05]. The number of patients with flares was similar in both groups [29%（21/72） vs 21.8%（12/55）,χ2=0.88, P=0.347]. Conclusion The strategy to reduce doses of rhTNFR：Fc produce similar clinical outcomes at 1 year in AS patients after reaching low disease activity, but is substantially less cosily.