重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合柳氮磺吡啶诱导缓解并维持治疗活动性强直性脊柱炎的临床研究

Recombinant human tumor necrosis factor receptor-Fc fusion protein combined with sulfasalzine in the induction and maintenance treatment of active ankylosing spondylitis

【摘要】目的探究在重组人Ⅱ型肿瘤坏死因子受体．抗体融合蛋白（益赛普，TNFR：Fe）总剂量300nag不变的前提条件下，联合柳氮磺吡啶（SASP）诱导缓解并维持治疗活动性As的优化用药方案。方法100例病程≤5年的As患者随机分为3组，G1组给予TNFR：Fc（25mg，每周2次），使用6周后改为SASP单药维持；G2组给予TNFR：Fc（25mg，每周1次），使用12周后改为SASP单药维持；G3组给予rhTNFR：Fc（25mg，每10d1次），使用17周后改为SASP单药维持，疗程共为24周。分别在0、6、12、18、24周进行随访，主要观察终点为第24周时，3种维持治疗方案实现“持续BASDAl50”的患者比例，并记录治疗过程中的所有事件，数据分析应用SPSS17．0软件，采用独立样本t检验和矿检验进行分析。结果G1、G2、G3组，BASDAl50在6周比例分别为90．6％、93．9％、85．7％（P-0．52）；在12周为100％、90．9％和88．6％（P：0．16），第18周分别为68．7％、81．8％和74-3％（P=0．47）；24周分别达到BASDAl50的比例37．5％、57．6％和68．6％（P=0．035）。G3组在24周达到BASDAl50的比例明显高于G1及G2组（P〈0．05）。结论TNFR：Fc联合SASP治疗6周可以达到缓解活动性AS的疗效，后期维持治疗阶段可以适当延长TNF阻断剂应用的周期。

Objective To evaluate the tosage regimen of sulfasalzine combined with recombinant human tumor necrosis factor receptor-Fc fusion protein （rhTNFR） in the induction and maintenance of remission in active ankylosing spondyhtis. Methods This study enrolled 100 ankylosing spondylitis patients with disease duration for less than five years who were treated with sulfasalzine and rhTNFR combination therapy. Patients were randomly assigned to three groups six weeks later： patients in the G! group received sutfasalzine combined with rhTNFR at a 25 mg dosage twice each week. Patients shifted to monotherapy with sulfasalzine six weeks later： patients in G2 group received sulfasalzine combined with rhTNFR at 25 mg dosage per week. Patients were switched to monotherapy of sulfasalzine twelve weeks later： patients in G3 group received sulfasalzine combined with rhTNFR at 25 mg dosage once every ten days.Patients were changed to monotherapy of sulfasalzine seventeen weeks later. The whole treatment lasted for 24 weeks. All participants were followed up at week 0, 6, 12, 18, 24 respectively and were evaluated by BASDAI 50. The primary end-point of this study was the percentage of patients achieved BASDAI 50 remission. Data were analyzed with SPSS version 17.0. Independent t-test andA test were adopted to analyze data. Results 90% of patients treated with combination therapy reached BASDAI50 at the 6th week. All patients in the G1 group achieved BASDAI 50 remission at 12th week, but the percentage dropped to 68.7% at 18th week, which gradually decreased to 37.5% at the 24th week. In G2 group, 93.9% patients reached BASDAI50, which declined to 81.8% at the 18th week. The whole number accounted for 60% at the end point of 24th week. In G3 group, 85.7% patients achieved BASDAI50 at the 12th week, accounted for 74.3% at 18th week, and declined to 68.6% at the 24th week. G3 group of patients presented a significantly higher rate than other groups（P〈0.05）. Conclusion Sulfasalzine and rhTNFR combination therapy can gain remission in active AS patients after treated for six weeks. Doctors may extend TNF antagonist treatment in order to achieve long-term remission.