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临床研究

Clinical trial of recombinant human Ⅱ tumor necrosis factor receptor-antibody fusion protein in the treatment of ankylosing spondylitis

目的观察重组人Ⅱ型肿瘤坏死因子受体抗体融合蛋白对强直性脊柱炎临床症状、炎症因子及活动度的影响。方法 78例强直性脊柱炎患者随机分为试验组和对照组,各39例。对照组口服柳氮磺胺吡啶1.0 g,每天2次,试验组在对照组的基础上皮下注射重组人Ⅱ型肿瘤坏死因子受体抗体融合蛋白25 mg+注射用水1 mL,每周2次,2组均连续治疗3个月。观察2组患者的临床症状、炎症因子、活动度和药物不良反应发生情况。结果试验组总有效率为94.87%(37/39例),对照组总有效率为71.79%(28/39例),2组差异有统计学意义(P<0.05)。试验组强直性脊柱炎病情活动指数(BASDAI)为2.39±0.35,脊柱痛为26.32±3.24,脊柱痛34.32±4.12,关节肿胀为(8.35±1.12)mm,晨僵时间为(18.74±2.32)min,对照组的BASDAI为3.51±0.62,脊柱痛30.21±3.52,脊柱痛45.23±5.21,关节肿胀为(10.42±1.50)mm,晨僵时间为(25.19±3.49)min,2组差异有统计学意义(P<0.05)。试验组C反应蛋白为(2.68±0.35)mg·L^(-1),肿瘤死因子-α为(82.36±8.54)ng·mL^(-1),白细胞介素-6为(14.12±1.56)pg·mL^(-1),白细胞介素-8为(24.31±3.45)μg·L^(-1);对照组C反应蛋白为(4.19±0.56)mg·L^(-1),肿瘤死因子-α为(112.34±12.45)ng·mL^(-1),白细胞介素-6(18.25±2.12)pg·mL^(-1),白细胞介素-8为(36.12±4.21)μg·L^(-1),2组差异有统计学意义(P>0.05)。试验组Schober试验为(5.08±0.60)cm,扩胸度为(5.12±0.66)cm,颈部旋度为(81.25±8.32)度,颈部旋度为(28.32±3.41)cm;对照组的Schober试验为(4.12±0.58)cm,扩胸度为(3.72±0.52)cm,颈部旋度为(66.74±8.58)度,颈部旋度为(20.02±2.45)cm,2组差异有统计学意义(P<0.05)。药物不良反应主要表现为局部红肿、瘙痒,试验组药物不良反应发生率为10.26%(4/39例),对照组为30.77%(12/39例),2组差异有统计学意义(P<0.05)。结论重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗有助于改善临床症状,降低炎症因子水平,增强关节活动度,安全性较好。

Objective To study the clinical effect of recombinant human Ⅱ tumor necrosis factor receptor -antibody fusion protein on clinical symptoms, inflammatory cytokines and activity of ankylosing spondylitis. Methods Seventy- eight patients with ankylosing spondylitis were randomly divided into treatment group and control group, each group 39 cases. Patients in control group received sulfasalazine 1.0 g, 2 times a day, patients in treatment group were treated with recombinant human 1~tumor necrosis factor receptor - antibody fu- sion protein 25 mg ± water 1 mL, 2 times a week oil the basis of control group. All patients were treated for 3 months. Clinical symptoms, inflammatory cytokines, activity and adverse reactions were compared between the two groups. Results Total effective rate in treatment group was 94. 87% （37/39）, had significant difference with 71.79% （28/39） in control group（P 〈0. 05）. Bath ankylosing spondylitis disease activity index（BASDAI）, spine pain, local tenderness and joint swelling pain, morning stiffness time in treatment group were （ 2. 39 - 0. 35 ）, （26. 32 ± 3.24 ）, （ 34. 32 ± 4. 12）, （8.35 ± 1.12 ） mm, （ 18.74 ± 2.32 ） min, had significant difference with （ 3.51 ± 0.62 ）, （ 30. 21 ± 3.52 ）, （45.23 ± 5.21 ）, （ 10. 42 ± 1.50 ） mm, （25.19 ± 3.49 ） min in control group （ P 〈 0.05 ）. C - reaction protein （ CRP）, tumor necrosis factor-α（TNF-α, interleukin（IL） -6, IL-8 levels in treatment group were （2. 68 ±0. 35） mg · L-1, （82.36 ± 8.54） ng· mL-1, （ 14. 12 ± 1.56） pg· mL-1 , （24. 31 ± 3.45） μg · L-1 , had significant difference with （4. 19±0.56）· L-1, （112. 34 ±12.45）ng· mL-1, （18.25 ±2.12）pg·mL-1, （36. 12±4.21）μg · L-1 in control group （P 〈 0. 05 ）. The Schober test, chest expansion degree, neck curl, lumbar scoliosis in treatment group were（5.08 ± 0. 60 ） cm, （ 5. 12 ± 0. 66 ） cm, （ 81.25 ± 8.32 ） o, （ 28.32 ± 3.41 ） cm, had significant difference with （4. 12 ±0. 58）cm,（3.72 ±0. 52） cm, （66. 74 ± 8.58）°, （20. 02 ±2. 45） cm in control group （P 〉0. 05）. The adverse drug reactions were mainly local swelling and itching. The incidence rate of adverse drug reactions in treatment group was 10. 26% （4/39）, had significant difference with 30. 77% （12/39） in control group （P 〈 0. 05）. Conclusion Recombi- nant human tumor necrosis factor receptor Ⅱ- antibody fusion protein therapy can help improve the clinical symptoms, reduce the content of inflammatory cytokines, enhancement joints activity, and good safety performance.