超声下滑膜炎减轻对肿瘤坏死因子抑制剂治疗类风湿关节炎临床应答的影响研究

Effect of Ultrasound-detected Improvement in Synovitis in Evaluating Clinical Response to Tumor Necrosis Factor Inhibitor in Rheumatoid Arthritis Patients

背景探索影响肿瘤坏死因子(TNF)抑制剂治疗类风湿关节炎(RA)临床疗效的因素有助于制定个体化治疗策略,提高RA治疗效率。超声作为低成本、易操作的影像学检查手段,检测关节滑膜炎水平可以预测关节损伤程度。目的评估超声下滑膜炎减轻对接受TNF抑制剂治疗的RA患者临床应答的预测作用。方法连续纳入2015年1月-2017年6月南华大学附属第一医院就诊的活动性RA患者80例,给予TNF抑制剂(依那西普25 mg/次,2次/周,皮下注射)治疗24周。分别于基线期(W0)、治疗4周后(W4)、治疗12周后(W12)以及治疗24周后(W24)利用超声检查双侧肩关节、腕关节、肘关节、膝关节、第1~5掌指关节和第1~5近端指间关节,并记录滑膜炎关节数。采用基于红细胞沉降率(ESR)的28关节疾病活动度评分〔DAS28(ESR)〕评估临床应答率。结果W0超声下滑膜炎关节数与RA患者压痛关节数(TJC)(r=0.452,P<0.001)、肿胀关节数(SJC)(r=0.454,P<0.001)、DAS28(ESR)评分(r=0.451,P<0.001)呈正相关;W4、W12、W24超声下滑膜炎关节数与DAS28(ESR)评分均呈正相关(r=0.451,P<0.001;r=0.369,P=0.001;r=0.534,P<0.001)。不同时间点超声下滑膜炎关节数比较,差异有统计学意义(P<0.05);其中W4、W12、W24超声下滑膜炎关节数少于W0,W12、W24超声下滑膜炎关节数少于W4,W24超声下滑膜炎关节数少于W12(P<0.05)。W4、W12、W24,临床应答患者分别为23例(28.8%)、41例(51.2%)、54例(67.5%)。W24临床应答与无应答患者W0、W4、W12、W24超声下滑膜炎关节数比较,差异均无统计学意义(P>0.05)。W4超声下滑膜炎减轻患者W24临床应答率高于未减轻患者(P<0.05);W12、W24超声下滑膜炎减轻与未减轻患者W24临床应答率比较,差异均无统计学意义(P>0.05)。结论超声下滑膜炎与RA疾病活动度呈正相关,且其短期内(W4)减轻可能对接受TNF抑制剂治疗患者的临床应答率有影响。

Background Exploring the factors influencing the efficacy of tumor necrosis factor(TNF)inhibitors in the treatment of rheumatoid arthritis(RA)can help to develop individualized treatment strategies and improve the efficiency of RA treatment.Synovitis status detected by ultrasound,a low-cost and easy-to-operate imaging method,may evaluate the joint damage from RA.Objective This study aimed to evaluate the value of ultrasound-detected improvement in synovitis in predicting the clinical response to TNF inhibitor therapy in RA patients.Methods 80 active RA patients from the First Affiliated Hospital of University of South China were consecutively enrolled from January 2015 to June 2017,and received TNF inhibitor therapy(etanercept 25 mg administered twice a week by subcutaneous injection)for 24 weeks.28 joints(bilateral shoulder joints,wrist joints,elbow joints,knee joints,1-5 metacarpophalangeal joints and 1-5 proximal interphalangeal joints)of RA patients were examined by ultrasound at baseline,4,12,and 24 weeks after treatment,and the number of synovitis joints measured at each time was recorded.The clinical response was assessed at different time points after initiation of treatment by DAS28-ESR score.Results The number of ultrasound-detected synovitis joints was positively correlated with TJC(r=0.452,P<0.001),SJC(r=0.454,P<0.001),and DAS28-ESR score(r=0.451,P<0.001)at baseline.At the end of the 4th,12th,and 24th weeks of treatment,the number of ultrasound-detected synovitis joints was positively correlated with the DAS28-ESR score(r=0.451,P<0.001;r=0.369,P=0.001;r=0.534,P<0.001).The number of ultrasound-detected synovitis joints differed significantly across the measurement time points(P<0.05).To be specific,it showed a successive decrease over the 4 measurements(P<0.05).The cases with response to TNF inhibitor therapy at the end of 4th,12th and 24th weeks of treatment numbered 23(28.8%),41(51.2%),and 54(67.5%),respectively.During the 24-week treatment,the number of ultrasound-detected synovitis joints measured at the 4 time points showed no significant differences between those with responses and those without(P>0.05).The overall clinical response rate at the end of treatment was higher in those with ultrasounddetected improvement in synovitis at the end of 4 weeks of treatment than that of those without(P<0.05).But the overall clinical response rate was not associated with ultrasound-detected improvement in synovitis after 12 and 24 weeks of treatment(P>0.05).Conclusion Ultrasound-detected synovitis status is positively correlated with RA activity.And improvement in synovitis in short-term(4-week)treatment detected by ultrasound may have an impact clinical response in RA patients treated with TNF inhibitor.