甲氨蝶呤联合托法替布/益赛普/来氟米特和柳氮磺吡啶对难治性类风湿关节炎患者的疗效比较

Evaluation of the efficacy of methotrexate combined with tofacitinib or etanercept or leflunomide plus sulfasalazine in the treatment of refractory rheumatoid arthritis

为比较甲氨蝶呤(methotrexate,MTX)联合托法替布(tofacitinib,TOF)/益赛普(etanercept,YSP)/来氟米特(leflunomide,LEF)及柳氮磺吡啶(sulfasalazine,SAZ)对难治性类风湿关节炎(refractory rheumatoid arthritis,RRA)患者的疗效,收集2019年3月至2020年9月于衡水市人民医院就诊的300例RRA患者作为研究对象,按照随机数字表法将患者分为TOF组、YSP组和LEF+SAZ组,每组各100例。所有患者常规给予MTX治疗,TOF组患者另给予TOF治疗,YSP组患者另给予YSP治疗,LEF+SAZ组患者另给予LEF+SAZ联合治疗。持续给药3组患者并观察6个月,比较他们接受治疗1、3、6个月后的临床疗效[美国风湿病学会(American College of Rheumatology,ACR)20、ACR50、ACR70]、疾病活动度评分(disease activity score 28,DAS28)、手腕部骨破坏评分(scoring radiographs in rheumatoid arthritis,SHARP)、炎性因子(IL-6和TNF-α)水平和不良反应发生情况。结果显示,治疗后3组患者的ACR20、ACR50和ACR70随治疗时间延长而逐渐升高,且治疗6个月后TOF组各项ACR应答率均显著高于YSP组和LEF+SAZ组(均P<0.05)。治疗后3组患者的DAS28、SHARP、IL-6和TNF-α水平均显著低于治疗前(均P<0.05),且治疗6个月后,TOF组上述指标(DAS28、SHARP、IL-6和TNF-α水平)均显著低于YSP组和LEF+SAZ组(均P<0.05)。治疗期间3组患者的不良反应发生率经对比差异无统计学意义(均P>0.05)。由此,MTX联合TOF可有效提高RRA患者的治疗效果,其在降低DAS28,提高临床疗效等方面显著优于MTX联合YSP或MTX联合LEF和SAZ,而三者安全性相当。

This study proposed to compare the therapeutic efficacy of methotrexate(MTX)combined respectively with tofacitinib(TOF),etanercept(YSP)or leflunomide(LEF)plus sulfasalazine(SAZ)in patients with refractory rheumatoid arthritis(RRA).A total of three hundred RRA patients were randomly divided into TOF group(one hundred cases),YSP group(one hundred cases),and LEF+SAZ group(one hundred cases).Patients in all three groups simultaneously received MTX treatment.Patients in the TOF,YSP,and LEF+SAZ groups were additionally given TOF,YSP,and LEF+SAZ treatment,respectively.All patients were treated and observed longitudinally for six months.The clinical efficacy([American College of Rheumatology,ACR]20,ACR50,ACR70),disease activity score 28(DAS28),scoring radiographs in rheumatoid arthritis(SHARP),levels of inflammatory factors(IL-6 and TNF-α)and the incidence of adverse reactions in all groups were observed after one,three and six months of treatment.The results showed that as the treatments progressed,the rate of ACR20,ACR50,and ACR70 in the three groups grew higher,and these above-mentioned indexes(ACR20,ACR50,ACR70)in the TOF group were significantly higher than those in the YSP group and the LEF+SAZ group after six months of treatments(all P<0.05).In addition,DAS28,SHARP,and the levels of IL-6 and TNF-αin the three post-therapy groups were lower than those before treatment,and in the TOF group these above-mentioned indexes(DAS28,SHARP,IL-6,TNF-α)were significantly lower than those in the YSP group and the LEF+SAZ group after six months of treatment(all P<0.05).There was no significant difference in the incidence of adverse reactions among the three groups during treatment(all P>0.05).In conclusion,MTX combined with TOF has effectively improved the symptoms of RRA patients.This medication is significantly better than MTX combined with YSP or MTX combined with LEF plus SAZ in reducing DAS28 and improving clinical efficacy,with all similar safety.