【作者】 梁爽；

【导师】 马宁；

【作者基本信息】 吉林大学 ， 临床医学硕士（内科学）（专业学位）， 2022， 硕士

【摘要】 背景及目的:原发性干燥综合征(p SS)是一种慢性炎症性自身免疫性疾病,以外分泌腺的淋巴细胞浸润和炎症为主要特征。常应用免疫抑制剂如羟氯喹、甲氨蝶呤、艾拉莫德等预防病情进展。目前尚缺乏不同免疫抑制剂间直接对比治疗p SS的有效性和安全性的研究数据。因此,本研究对艾拉莫德与羟氯喹治疗p SS的有效性与安全性进行了系统评价,以便为临床治疗方案的选择提供理论依据。方法:计算机检索Pub Med、The Cochrane Library、Embase、Web of Science以及中国生物医学文献数据库、维普期刊资源数据库、万方数据库、中国知网,从建库至2021年12月间有关艾拉莫德与羟氯喹治疗p SS有效性和安全性的随机对照试验(RCT)。由两名研究者根据制定的纳入和排除标准筛选出符合标准的文献,采用方法学质量评价标准进行文献质量评估并提取出纳入研究的资料数据。应用Rev Man 5.4软件进行Meta分析。结果:本研究共纳入12个RCT,包括1004名患者。从艾拉莫德治疗p SS的临床疗效,实验室指标及安全性三方面进行评价。1.疗效评价:Meta分析结果显示:艾拉莫德联合甲泼尼龙治疗p SS在提高临床总有效率[RR=1.23,95%CI(1.16,1.31),P<0.001],降低ESSDAI评分[MD=-1.94,95%CI(-2.55,-1.33),P<0.001],降低ESSPRI评分[MD=-2.16,95%CI(-2.98,-1.34),P<0.001],提高Schirmeri试验数值[MD=2.09,95%CI(1.62,2.56),P<0.001],提高唾液流率[MD=0.39,95%CI(0.29,0.49),P<0.001]方面优于羟氯喹联合甲泼尼龙。2.实验室指标:Meta分析结果显示:与羟氯喹联合甲泼尼龙相比,艾拉莫德联合甲泼尼龙治疗p SS能更有效的降低Ig G[MD=-2.96,95%CI(-3.55,-2.37),P<0.001],降低ESR[MD=-5.67,95%CI(-8.02,-3.33),P<0.001],降低RF[MD=-4.53,95%CI(-5.80,-3.25),P<0.001],升高PLT[MD=11.29,95%CI(7.53,15.06),P<0.001],降低CD19~+CD27~+B细胞百分率[MD=-0.04,95%CI(-0.06,-0.02),P<0.001],降低ACL[MD=-0.33,95%CI(-0.50,-0.16),P<0.001]。3.安全性评价:艾拉莫德联合甲泼尼龙与羟氯喹联合甲泼尼龙治疗p SS的不良反应总发生率差异无统计学意义[RR=0.69,95%CI(0.47,1.00),P=0.05],二者安全性相当。结论:1.艾拉莫德联合甲泼尼龙治疗p SS在缓解患者临床症状方面优于羟氯喹联合甲泼尼龙。2.与羟氯喹联合甲泼尼龙相比,艾拉莫德联合甲泼尼龙能更有效的改善p SS患者实验室指标,如降低Ig G、RF、ESR水平,升高PLT水平。3.艾拉莫德联合甲泼尼龙与羟氯喹联合甲泼尼龙治疗p SS的安全性相当,无严重不良反应。更多还原

【Abstract】 Background and objective:Primary Sjogren’s syndrome(p SS)is a chronic inflammatory autoimmune disease characterized by lymphocyte infiltration and inflammation of the exocrine glands.Hydroxychloroquine,methotrexate,and Iguratimod are commonly used to prevent disease progression in Patients.There is a lack of data on the efficacy and safety of direct comparison of p SS between different immunosuppressants.Therefore,this study systematically evaluated the efficacy and safety of Iguratimod and hydroxychloroquine in the treatment of p SS in order to provide a theoretical basis for the choice of clinical treatment options.Methods:Pub Med,The Cochrane Library,Embase,Web of Science,CBM,VIP,CNKI and Wan Fang Data databases were electronically searched to gather randomized controlled trials(RCTs)on the effectiveness and safety of Iguratimod and hydroxy-chloroquine in the treatment of p SS from the establishment of the database to December 2021.According to the included and exclusion criteria,two researchers screened literatures that meet the criteria,used methodological quality evaluation standards to evaluate the quality of the literature,and extracted information from the included studies.Rev Man 5.4 software was used to perform Meta analysis.Results:A total of 12 RCTs involving 1004 patients were enrolled.This study evaluated the clinical efficacy,laboratory indicators and safety of Iguratimod in the treatment of p SS.1.Clinical efficacy:Meta-analysis results showed that:Iguratimod combined with methylprednisolone increased total treaement efficicency[RR=1.23,95%CI(1.16,1.31),P<0.001],decreased ESSDAI score[MD=-1.94,95%CI(-2.55,-1.33),P<0.001],decreased ESSPRI score[MD=-2.16,95%CI(-2.98,-1.34),P<0.001],increased Schirmeri test value[MD=2.09,95%CI(1.62,2.56),P<0.001],increased saliva flow rate[MD=0.39,95%CI(0.29,0.49),P<0.001]better than hydroxy-chloroquine combined with methylprednisolone in the treatment of p SS.2.laboratory indicators:Meta-analysis results showed that:Compared with the hydroxychloroquine group,the treatment of p SS in the Iguratimod group was more effective in reducing Ig G[MD=-2.96,95%CI(-3.55,-2.37),P<0.001],ESR[MD=-5.67,95%CI(-8.02,-3.33),P<0.001]and RF[MD=-4.53,95%CI(-5.80,-3.25),P<0.001],increasing PLT[MD=11.29,95%CI(7.53,15.06),P<0.001],decreasing the percentage of CD19~+CD27~+B cells[MD=-0.04,95%CI(-0.06,-0.02),P<0.001),and ACL[MD=-0.33,95%CI(-0.50,-0.16),P<0.001].3.Safety evaluation:There were no significant differences in the total incidence of adverse reactions in the treatment of p SS between the Iguratimod group and the hydroxychloroquine group[RR=0.69,95%CI(0.47,1.00),P=0.05].The safety of two groups was similar.Conclusion:1.The Iguratimod combined with methylprednisolone was superior to hydroxy-chloroquine combined with methylprednisolone in alleviating clinical symptoms of p SS.2.Compared with hydroxychloroquine group,Iguratimod group can improve laboratory indicators of p SS patients more effectively,such as reducing Ig G,RF,ESR levels and increasing PLT levels.3.There were no serious adverse reactions in the treatment of p SS with Iguratimod combined with methylprednisolone,and the safety was similar to hydroxychloroquine combined with methylprednisolone.更多还原