重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗类风湿关节炎疗效及对血清MK和Th17/Terg的影响
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摘要
目的探讨注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(recom binant human tumor necrosis factor receptor-Fc fusion protein,rhTNFR:Fc)治疗类风湿关节炎(RA)疗效及对血清中期因子(MK)和辅助性T细胞17/调节性T细胞(Th17/Terg)的影响。方法选择2016年1月至2018年5月免疫科收治的52例RA患者,随机数字表法分为2组,每组26例。研究组患者接受rhTNFR:Fc 25 mg皮下注射,每周2次,对照组患者口服甲氨蝶呤7.5～15 mg/次,1周1次,2组均治疗24周。比较2组治疗前后压痛关节数(TJC)、肿胀关节数(SJC)、晨僵持续时间(MST)、DAS28-3、CDAI差异,血清MK、Th17/Terg细胞水平的变化,用斯坦福健康评价问卷(HAQ)和健康测量量表(SF-36)评价2组患者治疗前后功能状态和生活质量。结果 2组患者治疗后TJC、SJC、MST、DAS28-3、CDAI均显著下降(P<0.05),研究组患者治疗后TJC、SJC、MST、DAS28-3、CDAI低于对照组[(0.52±0.32)VS(0.63±0.49)、(0.41±0.02)VS(0.67±0.09)、(12.93±3.51)min VS(14.72±4.99)min、(1.41±0.69)VS(1.87±0.98)、(2.03±1.15)VS(2.65±1.48),P<0.05]。研究组患者治疗后MK、Th17细胞比例、Th17/Treg水平低于对照组[(63.02±12.51)ng/L VS(104.21±23.64)ng/L、(3.14±0.28)%VS(3.97±0.38)%、(1.02±0.24)VS(1.32±0.35),P<0.05],Treg细胞比例高于对照组[(4.63±0.93)%VS(4.12±0.52)%,P<0.05]。研究组治疗后HAQ低于对照组[(0.98±0.06)分VS(1.36±0.13)分,P<0.05],SF-36评分高于对照组[(52.26±6.01)分VS(45.89±2.21)分,P<0.05]。研究组不良反应率为15.38%,对照组为23.08%,2组比较差异无统计学意义(P>0.05)。结论 rhTNFR:Fc可显著改善RA临床症状,减轻RA活动度,并可降低血清MK,促进Th17/Treg平衡,提高患者关节功能和生活质量。
Objective To explore the therapeutic effects of recombinant human tumor necrosis factor receptor-Fc fusion protein(rhTNFR:Fc) on rheumatoid arthritis(RA) and its effects on serum MK and Th17/Terg of patients with RA.Methods Fifty-two patients with RA who were admitted and treated in our hospital from January 2016 to May 2018 were randomly divided into control group(n=29) and research group(n=29).The patients in research group were treated by subcutaneous injection of rhTNFR 25 mg,twice a week,however, the patients in control group were treated by oral methotrexate 7.5～15 mg,once a week,with a treatment course of 24 weeks for both groups. The changes of the number of joint tenderness(TJC) and swelling joints(SJC), the duration of morning stiffness(MST), DAS283, CDAI, as well as the changes of serum levels of MK and Th17/Terg before and after the treatment were observed and compared between the two groups. Moreover, HAQ and SF36 were used to evaluate the functional status and life quality of the patients before and after treatment in both groups.Results After treatment, the TJC, SJC, MST, DAS283 and CDAI were decreased significantly in both groups(P<0.05). The TJC, SJC, MST, DAS283 and CDAI in research group were significantly lower than those in control group[(0.52±0.32) vs(0.63±0.49),(0.41±0.02) vs(0.67±0.09),(12.93±3.51)min vs(14.72± 4.99)min,(1.41±0.69) vs(1.87±0.98),(2.03±1.15) vs(2.65±1.48),P<0.05]. Moreover, the proportion of MK and Th17 cells and the levels of Th17/Treg in research group were significantly lower than those in control group[(63.02±12.51)ng/L vs(104.21±23.64)ng/L,(3.14±0.28)% vs(3.97±0.38)%,(1.02±0.24) vs(1.32±0.35),P<0.05].Whereas the proportion of Treg cells in research group was significantly higher than that in control group [(4.63±0.93)% vs(4.12±0.52)%,P<0.05].Furthermore, the score of HAQ of the patients in research group(0.98±0.06) was significantly lower than that(1.36±0.13) in control group(P<0.05). And the score of SF36 in research group(52.26±6.01)was significantly higher than that(45.89±2.21) in control group(P<0.05).In addition, there was no statistical difference in the incidence rate of adverse reaction between the two groups(15.38% vs 23.08%,P>0.05).Conclusion Recombinant human tumor necrosis factor receptor antibody fusion protein can significantly improve the clinical symptoms of RA, reduce the activity of antibady and serum MK levels,which can promote the balance of Th17/Treg and improve the joint function and life quality of the patients.
Objective To explore the therapeutic effects of recombinant human tumor necrosis factor receptor-Fc fusion protein(rhTNFR:Fc) on rheumatoid arthritis(RA) and its effects on serum MK and Th17/Terg of patients with RA.Methods Fifty-two patients with RA who were admitted and treated in our hospital from January 2016 to May 2018 were randomly divided into control group(n=29) and research group(n=29).The patients in research group were treated by subcutaneous injection of rhTNFR 25 mg,twice a week,however, the patients in control group were treated by oral methotrexate 7.5～15 mg,once a week,with a treatment course of 24 weeks for both groups. The changes of the number of joint tenderness(TJC) and swelling joints(SJC), the duration of morning stiffness(MST), DAS283, CDAI, as well as the changes of serum levels of MK and Th17/Terg before and after the treatment were observed and compared between the two groups. Moreover, HAQ and SF36 were used to evaluate the functional status and life quality of the patients before and after treatment in both groups.Results After treatment, the TJC, SJC, MST, DAS283 and CDAI were decreased significantly in both groups(P<0.05). The TJC, SJC, MST, DAS283 and CDAI in research group were significantly lower than those in control group[(0.52±0.32) vs(0.63±0.49),(0.41±0.02) vs(0.67±0.09),(12.93±3.51)min vs(14.72± 4.99)min,(1.41±0.69) vs(1.87±0.98),(2.03±1.15) vs(2.65±1.48),P<0.05]. Moreover, the proportion of MK and Th17 cells and the levels of Th17/Treg in research group were significantly lower than those in control group[(63.02±12.51)ng/L vs(104.21±23.64)ng/L,(3.14±0.28)% vs(3.97±0.38)%,(1.02±0.24) vs(1.32±0.35),P<0.05].Whereas the proportion of Treg cells in research group was significantly higher than that in control group [(4.63±0.93)% vs(4.12±0.52)%,P<0.05].Furthermore, the score of HAQ of the patients in research group(0.98±0.06) was significantly lower than that(1.36±0.13) in control group(P<0.05). And the score of SF36 in research group(52.26±6.01)was significantly higher than that(45.89±2.21) in control group(P<0.05).In addition, there was no statistical difference in the incidence rate of adverse reaction between the two groups(15.38% vs 23.08%,P>0.05).Conclusion Recombinant human tumor necrosis factor receptor antibody fusion protein can significantly improve the clinical symptoms of RA, reduce the activity of antibady and serum MK levels,which can promote the balance of Th17/Treg and improve the joint function and life quality of the patients.
引文
1 叶杨,杨南萍,高晓梅.注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对活动性类风湿关节炎患者骨代谢的影响.中国医院药学杂志,2018,38:514-519.
2 李永红,王凛介,朱科达.小剂量肾上腺糖皮质激素与注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白短期联合应用治疗类风湿关节炎临床效果观察.实用医院临床杂志,2017,14:232-235.
3 李光韬,许玉峰,王昱,等.注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤治疗活动性类风湿关节炎磁共振影像对比研究.中国实用内科杂志,2017,37:227-232.
4 Felson DT,Anderson JJ,Boers M,et al.American college of rheumatology preliminary definition of improvement in rheumatoid arthritis.Arthritis Rheum,1995,6:727-735.
5 van der Heijde DM,van ’t Hof MA,van Riel PL,et al.Judging disease activity in clinical practice in rheumatoid arthritis:first step in the development of a disease activity score.Ann Rheum Dis,1990,49:916-920.
6 Smolen JS,Breedveld FC,Schiff MH,et al.A simplified disease activity index for rheum atoid arthritis for use in clinical practice.Rheumatology(Oxford),2003,42:244-257.
7 叶军,陈亚宝,徐洪涛,等.流式细胞术不同设门方法对 CD+4 CD+25调节性 T 细胞的检测方法比较.中华生物医学工程杂志,2010,16:495-498.
8 谭颖.重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合心理干预治疗类风湿性关节炎的疗效及经济学评价.中国药业,2016,25:40-42.
9 林陈拉,徐一松,张佳欢.ICU护理质量敏感指标和SF-36健康调查量表的应用.浙江医学教育,2017,16:46-48.
10 赵进军,欧阳晴晴,王然,等.人Ⅱ型肿瘤坏死因子受体与抗体融合蛋白治疗类风湿性膝关节炎疗效.中国临床研究,2016,29:62-64.
11 毕丹艳,李芹,张虹,等.雷公藤多苷联合甲氨蝶呤治疗类风湿关节炎的临床疗效研究.中国临床药理学杂志,2016,32:880-882.
12 黄慧,俞海国,钱小青,等.甲氨蝶呤片联合注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗全身型幼年特发性关节炎的临床研究.中国临床药理学杂志,2016,32:2231-2234.
13 李文思,陈璋璋,吕迁洲.肿瘤坏死因子α-308G/多态性与类风湿关节炎疾病及肿瘤坏死因子α抑制剂疗效的相关性研究进展.临床内科杂志,2015,32:570-572.
14 庞琳烜,杨西超,郑朝晖,等.重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白与免疫抑制剂治疗强直性脊柱炎临床观察.解放军医药杂志,2016,28:92-95,104.
15 王京旭,李连菊,李晓丽.艾拉莫德联合重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗类风湿关节炎的临床研究.现代药物与临床,2017,32:2221-2225.
16 Bathon JM,Matin RW,Fleischmann RM,et al.A comparison of Etanercept and methotrexate in patients with early rheumatoid arthritis.New Eng J Med,200,343:1586-1593.
17 马信文,董泽民,王勇,等.血清MK和Th17/调节性T细胞对类风湿关节炎患者病情发生发展的影响.海南医学,2017,28:2128-2130.
2 李永红,王凛介,朱科达.小剂量肾上腺糖皮质激素与注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白短期联合应用治疗类风湿关节炎临床效果观察.实用医院临床杂志,2017,14:232-235.
3 李光韬,许玉峰,王昱,等.注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤治疗活动性类风湿关节炎磁共振影像对比研究.中国实用内科杂志,2017,37:227-232.
4 Felson DT,Anderson JJ,Boers M,et al.American college of rheumatology preliminary definition of improvement in rheumatoid arthritis.Arthritis Rheum,1995,6:727-735.
5 van der Heijde DM,van ’t Hof MA,van Riel PL,et al.Judging disease activity in clinical practice in rheumatoid arthritis:first step in the development of a disease activity score.Ann Rheum Dis,1990,49:916-920.
6 Smolen JS,Breedveld FC,Schiff MH,et al.A simplified disease activity index for rheum atoid arthritis for use in clinical practice.Rheumatology(Oxford),2003,42:244-257.
7 叶军,陈亚宝,徐洪涛,等.流式细胞术不同设门方法对 CD+4 CD+25调节性 T 细胞的检测方法比较.中华生物医学工程杂志,2010,16:495-498.
8 谭颖.重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合心理干预治疗类风湿性关节炎的疗效及经济学评价.中国药业,2016,25:40-42.
9 林陈拉,徐一松,张佳欢.ICU护理质量敏感指标和SF-36健康调查量表的应用.浙江医学教育,2017,16:46-48.
10 赵进军,欧阳晴晴,王然,等.人Ⅱ型肿瘤坏死因子受体与抗体融合蛋白治疗类风湿性膝关节炎疗效.中国临床研究,2016,29:62-64.
11 毕丹艳,李芹,张虹,等.雷公藤多苷联合甲氨蝶呤治疗类风湿关节炎的临床疗效研究.中国临床药理学杂志,2016,32:880-882.
12 黄慧,俞海国,钱小青,等.甲氨蝶呤片联合注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗全身型幼年特发性关节炎的临床研究.中国临床药理学杂志,2016,32:2231-2234.
13 李文思,陈璋璋,吕迁洲.肿瘤坏死因子α-308G/多态性与类风湿关节炎疾病及肿瘤坏死因子α抑制剂疗效的相关性研究进展.临床内科杂志,2015,32:570-572.
14 庞琳烜,杨西超,郑朝晖,等.重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白与免疫抑制剂治疗强直性脊柱炎临床观察.解放军医药杂志,2016,28:92-95,104.
15 王京旭,李连菊,李晓丽.艾拉莫德联合重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗类风湿关节炎的临床研究.现代药物与临床,2017,32:2221-2225.
16 Bathon JM,Matin RW,Fleischmann RM,et al.A comparison of Etanercept and methotrexate in patients with early rheumatoid arthritis.New Eng J Med,200,343:1586-1593.
17 马信文,董泽民,王勇,等.血清MK和Th17/调节性T细胞对类风湿关节炎患者病情发生发展的影响.海南医学,2017,28:2128-2130.
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