托珠单抗联合改善病情抗风湿药治疗中重度类风湿关节炎短期临床观察
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摘要
目的:研究托珠单抗联合改善病情抗风湿药(DMARDs)治疗中重度活动性类风湿关节炎(RA) 12周临床疗效及不良反应。方法:20例中重度活动的RA患者分别在0周、4周、8周接受托珠单抗8 mg/kg治疗,同时予以DMARDs治疗,在4周、8周、12周观察疗效及不良反应。观察指标为血沉、C反应蛋白(CRP)、类风湿因子(RF)、血红蛋白、血小板、疾病活动度评分(DAS28)、肝功能、肾功能、患者对疾病总体评价和医生对疾病总体评价及美国风湿病学会疗效评价指标(ACR20、ACR50)。结果:与治疗前相比,20例RA患者在4周、8周、12周时血沉、CRP、RF、血小板均明显下降,差异均有统计学意义(P<0. 01); DAS28在治疗4周时明显改善,在治疗8周时进一步改善,差异均有统计学意义(P <0. 01);而血红蛋白在4周时明显上升,到12周时进一步上升,差异均有统计学差异(P <0. 01);患者和医生总体评价评分持续性下降,差异有统计学意义(P <0. 01);在8周和12周时达到ACR20者达90%、95%,达到ACR50者达80%、90%; 20例患者中有1例出现上呼吸道感染,但无严重感染、肝肾损害及过敏反应发生。结论:托珠单抗联合DMARDs治疗RA短期之内即改善患者的症状体征及炎症指标,且无明显不良反应发生。
AIM: To study the clinical efficacy and adverse reactions of tocilizumab combined with disease modifying antirheumatic drugs( DMARDs)in the treatment of moderate-to-severe active rheumatoid arthritis( RA) for 12 weeks. METHODS:Twenty patients with moderate-to-severe active RA were treated with 8 mg/kg of tocilizumab at 0,4 th,and 8 th week and treated with DMARDs. The effects and adverse reactions were observed at 4 th week,8 th week and 12 th week. The observed indicators were erythrocyte sedimentation rate( ESR),C-reactive protein( CRP),rheumatoid factor( RF),hemoglobin,platelet, DAS28, hepatic function, renal function,ACR20,ACR50,overall evaluation of the patient and physician to disease. RESULTS: Compared with baseline,ESR,CRP,RF and platelet counts in 20 RA patients were significantly decreased at 4 th week,8 th week,and 12 th week,and the difference was statistically significant( P <0. 01); DAS28 was significantly improved at 4 th week of treatment,and further improved at 8 th week of treatment,the difference was statistically significant( P < 0. 01); and hemoglobin increased significantly at 4 th weeks,and further increased at 12 th week,the difference was statistically significant( P< 0. 01). The overall evaluation scores of the patients and doctors decreased continuously,the difference was statistically significant( P < 0. 01); At 8 th week and 12 th week,ACR20 reached 90%,95%,and ACR50 reached 80%,90%; 1 of 20 patients appeared upper respiratory tract infection, there were no liver,kidney and hypersensitivity reactions.CONCLUSION: Tocilizumab combined with DMARDs in the treatment of RA within a short period of time improve the patient's symptoms,signs and inflammation indicators with no significant adverse reactions occurred.
AIM: To study the clinical efficacy and adverse reactions of tocilizumab combined with disease modifying antirheumatic drugs( DMARDs)in the treatment of moderate-to-severe active rheumatoid arthritis( RA) for 12 weeks. METHODS:Twenty patients with moderate-to-severe active RA were treated with 8 mg/kg of tocilizumab at 0,4 th,and 8 th week and treated with DMARDs. The effects and adverse reactions were observed at 4 th week,8 th week and 12 th week. The observed indicators were erythrocyte sedimentation rate( ESR),C-reactive protein( CRP),rheumatoid factor( RF),hemoglobin,platelet, DAS28, hepatic function, renal function,ACR20,ACR50,overall evaluation of the patient and physician to disease. RESULTS: Compared with baseline,ESR,CRP,RF and platelet counts in 20 RA patients were significantly decreased at 4 th week,8 th week,and 12 th week,and the difference was statistically significant( P <0. 01); DAS28 was significantly improved at 4 th week of treatment,and further improved at 8 th week of treatment,the difference was statistically significant( P < 0. 01); and hemoglobin increased significantly at 4 th weeks,and further increased at 12 th week,the difference was statistically significant( P< 0. 01). The overall evaluation scores of the patients and doctors decreased continuously,the difference was statistically significant( P < 0. 01); At 8 th week and 12 th week,ACR20 reached 90%,95%,and ACR50 reached 80%,90%; 1 of 20 patients appeared upper respiratory tract infection, there were no liver,kidney and hypersensitivity reactions.CONCLUSION: Tocilizumab combined with DMARDs in the treatment of RA within a short period of time improve the patient's symptoms,signs and inflammation indicators with no significant adverse reactions occurred.
引文
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[2]杨红,林彬,杨宏,等.艾拉莫德对类风湿关节炎患者血管内皮生长因子及色素上皮衍生因子表达的影响[J].中国临床药理学与治疗学,2017,22(1):68-71.
[3]Buch MH. Defining refractory rheumatoid arthritis[J]. Ann Rheum Dis,2018,77(7):966-969.
[4]Madhok R,Crilly A,Watson J,et al. Serum interleukin 6 levels in rheumatoid arthritis:correlations with clinical and laboratory indices of disease activity[J].Ann Rheum Dis,1993,52(3):232-234.
[5]Kotake S,Sato K,Kim KJ,et al. Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation[J]. J Bone Miner Res,1996,11(1):88-95.
[6]史群,赵岩,鲍春德,等.托珠单抗联合改善病情抗风湿药治疗类风湿关节炎的多中心、随机、双盲、安慰剂对照临床研究[J].中华内科杂志,2013,52(4):323-329.
[7]Lin CT,Huang WN,Hsieh CW,et al. Safety and effectiveness of tocilizumab in treating patients with rheumatoid arthritis-A three-year study in Taiwan[J].J Microbiol Immunol Infect,2017,17(3):1-10.
[8]Kremer JM,Blanco R,Halland AM,et al. Clinical efficacy and safety maintained up to 5 years in patients with rheumatoid arthritis treated with tocilizumab in a randomised trial[J]. Clin Exp Rheumatol,2016,34(4):625-633.
[9]Abdulkader OAF,Qushmaq K,Aljishi F. Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs or anti-tumor necrosis factor[J]. Ann Saudi Med,2016,36(3):190-196.
[10]Choy EH,Isenberg DA,Garrood T,et al. Therapeutic benefit of blocking interleukin-6 activity with an antiinterleukin-6 receptor monoclonal antibody in rheumatoid arthritis:a randomized,double-blind,placebocontrolled dose-escalation trial[J]. Arthritis Rheum,2002,46(12):3143-3150.
[11]Campbell L,Chen C,Bhagat SS,et al. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab:a systematic literature review and meta-analysis of randomized controlled trials[J]. Rheumatology,2011,50(3):552-562.
[12]姜楠,费允云,赵岩.白细胞介素-6阻断剂在类风湿关节炎的治疗应用[J].中华临床免疫和变态反应杂志,2012,6(3):232-236.
[13]Schinnerling K,Aguillón JC,Catalán D,et al. The role of interleukin-6 signalling and its therapeutic blockage in skewing the T cell balance in rheumatoid arthritis[J]. Clin Experimental Immunol,2017,189(1):12-20.
[14]Narazaki M,Tanaka T,Kishimoto T. The role and therapeutic targeting of IL-6 in rheumatoid arthritis[J]. Expert Rev Clin Immunol,2017,13(6):535-551.
[15]Abu-Shakra M,Zisman D,Balbir-Gurman A,et al.Effect of tocilizumab on fatigue and bone mineral density in patients with rheumatoid arthritis[J]. Isr Med Assoc J,2018,20(4):239-244.
[16]孙丽君,林玮,闰永龙,等.难治性类风湿关节炎托珠单抗治疗临床观察[J].河北医药,2016,38(24):3758-3764.
[17]孙芳芳,叶霜.托珠单抗联合甲氨蝶呤治疗难治性类风湿关节炎的疗效观察[J].上海交通大学学报,2016,36(11):1640-1647.
[18]尚可,皮慧,王友莲.托珠单抗注射液治疗32例难治性活动性类风湿关节炎的临床观察[J].中华风湿病学杂志,2015,19(7):451-454.
[19]Scott LJ. Tocilizumab:a review in rheumatoid arthritis[J]. Drugs,2017,77(17):1865-1879.
[20]Romano C,Del Mastro A,Sellitto A,et al. Tocilizumab reduces complement C3 and C4 serum levels in rheumatoid arthritis patients[J]. Clin Rheumatol,2018,37(6):1695-1700.
[2]杨红,林彬,杨宏,等.艾拉莫德对类风湿关节炎患者血管内皮生长因子及色素上皮衍生因子表达的影响[J].中国临床药理学与治疗学,2017,22(1):68-71.
[3]Buch MH. Defining refractory rheumatoid arthritis[J]. Ann Rheum Dis,2018,77(7):966-969.
[4]Madhok R,Crilly A,Watson J,et al. Serum interleukin 6 levels in rheumatoid arthritis:correlations with clinical and laboratory indices of disease activity[J].Ann Rheum Dis,1993,52(3):232-234.
[5]Kotake S,Sato K,Kim KJ,et al. Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation[J]. J Bone Miner Res,1996,11(1):88-95.
[6]史群,赵岩,鲍春德,等.托珠单抗联合改善病情抗风湿药治疗类风湿关节炎的多中心、随机、双盲、安慰剂对照临床研究[J].中华内科杂志,2013,52(4):323-329.
[7]Lin CT,Huang WN,Hsieh CW,et al. Safety and effectiveness of tocilizumab in treating patients with rheumatoid arthritis-A three-year study in Taiwan[J].J Microbiol Immunol Infect,2017,17(3):1-10.
[8]Kremer JM,Blanco R,Halland AM,et al. Clinical efficacy and safety maintained up to 5 years in patients with rheumatoid arthritis treated with tocilizumab in a randomised trial[J]. Clin Exp Rheumatol,2016,34(4):625-633.
[9]Abdulkader OAF,Qushmaq K,Aljishi F. Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs or anti-tumor necrosis factor[J]. Ann Saudi Med,2016,36(3):190-196.
[10]Choy EH,Isenberg DA,Garrood T,et al. Therapeutic benefit of blocking interleukin-6 activity with an antiinterleukin-6 receptor monoclonal antibody in rheumatoid arthritis:a randomized,double-blind,placebocontrolled dose-escalation trial[J]. Arthritis Rheum,2002,46(12):3143-3150.
[11]Campbell L,Chen C,Bhagat SS,et al. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab:a systematic literature review and meta-analysis of randomized controlled trials[J]. Rheumatology,2011,50(3):552-562.
[12]姜楠,费允云,赵岩.白细胞介素-6阻断剂在类风湿关节炎的治疗应用[J].中华临床免疫和变态反应杂志,2012,6(3):232-236.
[13]Schinnerling K,Aguillón JC,Catalán D,et al. The role of interleukin-6 signalling and its therapeutic blockage in skewing the T cell balance in rheumatoid arthritis[J]. Clin Experimental Immunol,2017,189(1):12-20.
[14]Narazaki M,Tanaka T,Kishimoto T. The role and therapeutic targeting of IL-6 in rheumatoid arthritis[J]. Expert Rev Clin Immunol,2017,13(6):535-551.
[15]Abu-Shakra M,Zisman D,Balbir-Gurman A,et al.Effect of tocilizumab on fatigue and bone mineral density in patients with rheumatoid arthritis[J]. Isr Med Assoc J,2018,20(4):239-244.
[16]孙丽君,林玮,闰永龙,等.难治性类风湿关节炎托珠单抗治疗临床观察[J].河北医药,2016,38(24):3758-3764.
[17]孙芳芳,叶霜.托珠单抗联合甲氨蝶呤治疗难治性类风湿关节炎的疗效观察[J].上海交通大学学报,2016,36(11):1640-1647.
[18]尚可,皮慧,王友莲.托珠单抗注射液治疗32例难治性活动性类风湿关节炎的临床观察[J].中华风湿病学杂志,2015,19(7):451-454.
[19]Scott LJ. Tocilizumab:a review in rheumatoid arthritis[J]. Drugs,2017,77(17):1865-1879.
[20]Romano C,Del Mastro A,Sellitto A,et al. Tocilizumab reduces complement C3 and C4 serum levels in rheumatoid arthritis patients[J]. Clin Rheumatol,2018,37(6):1695-1700.