重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗强直性脊柱炎的减量探索

A study of how to taper the dosage of recombinant human tumor necrosis factor receptor-Fc fusion protein in the treatment of ankylosing spondylitis

目的探索一种经济、有效、安全的强直性脊柱炎(AS)患者应用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(益赛普)的减量方法。方法对入选的48例活动期AS患者随机分为A、B两组,进行1年的疗效观察。两组患者均接受益赛普治疗,初始剂量为25mg每周2次皮下注射,当疾病得到缓解(BASDAI<2;ESR男<15mm/h,女<20mm/h;CRP<0.8mg/dl;PLT<300×109/L),即将益赛普每隔2个月逐渐减量。如果减量使患者症状加重或ESR、CRP、PLT计数等炎性指标反弹至异常水平,则将益赛普重新调回前一个剂量,并于下次复查时评估以确定益赛普的剂量。A组患者同时接受柳氮磺吡啶(SSZ)口服治疗,初始剂量为0.25tid,第2周增至0.5bid,第3周增至0.75bid,第4周增至1.0bid维持至第24周。结果两组患者前2个月均使用推荐剂量的益赛普即25mg每周2次皮下注射,均取得令人满意的疗效,起效快,缓解率高,组间差别无统计学意义。病情获得缓解的病例从第3个月起减量至25mg每周1次,至第4个月末评估疗效,达到ASAS20的百分数A组明显高于B组,且差异具有统计学意义(P<0.05)。随着用药间隔逐渐延长,两组间的差距越来越大。当益赛普减量至25mg每2周1次后,组间差别更是达到P<0.01。结论 SSZ联合益赛普治疗AS可取得较高的疾病缓解率或低疾病活动状态,可明显延长益赛普的用药间隔。

Objective To explore a economic and effective regimen of how to taper the dosage of recombinant human tumor necrosis factor receptor-Fc fusion protein （rhTNFR-Fc） in the treatment of ankylosing spondylitis （AS）. Methods In a 1-year study,forty-eight patients with active AS were divided into A and B groups randomized. All of them received the treatment of injecting rhTNFR-Fc. Initially took 25 mg rhTNFR-Fc hypodermic injection twice a week. After the disease was well controlled [ Bath ankylosing spondyhitis disease activity index 〈 2. 0, erythrocyte sedimentation rate （ESR） male 〈 15mm/h, female 〈 20 mm/h, and C-reactive protein（CRP） 〈0. 8 mg/dl, platelet 〈 300 10^9/L], rhTNFR-Fc dosage was gradually reduced in a 2-month step. The rhTNFR-Fc would come back to the former dosage if back pain, peripheral arthritis, extraarticular manifestations were aggravated or CRP or ESR or PLT were rebounded. And reassessed rhTNFR-Fc dosage after two monthes. Patients in group A took sulfasalazine concomitantly, initially took 0. 25 tid orally, the second week took 0. 5 bid,the third week up to O. 75 bid,the forth week 1.0 bid continued to the end of the trail. Results The disease was well controlled in most patients of both groups in the initial two months, there was no significant difference in patients reaching ASAS20 in the end of the first month and the second month between the two groups. The dosage of rhTNFR-Fc was reduced to 25 mg once a week in the beginning of the third month in patients whose disease were well controlled, as a result, there was significant difference in patients reaching ASAS20 in the end of the forth month （P 〈 0. 05 ）. The longer duration the rhTNFR-Fc was not injected, the bigger differet efficacy between the two groups. After the dosage of rhTNFR-Fc was reduced to 25 mg q2W, there was more significant difference between the two groups （ P 〈 0.01 ）. Conclusion The combined regimen of taking sulfasalazine orally and injecting rhTNFR-Fc in the treatment of active AS can well control the disease, and can reduce the dosage of rhTNFR-Fc significantly.