罗浮山风湿膏药治疗类风湿关节炎腕关节炎的多中心随机双盲对照临床研究

Rheumatoid arthritis combined with wrist inflammation treated with Luofushan Rheumatism Plaster:a randomized,double⁃blind,placebo⁃controlled,multicenter clinical trial

目的评价罗浮山风湿膏药治疗类风湿关节炎(rheumatoid arthritis,RA)腕关节炎的临床疗效和安全性。方法采用多中心、区组随机、双盲、安慰剂对照临床试验方法,收集8家医院RA合并腕关节腱鞘炎和(或)滑膜炎患者180例,按照1∶1比例区组随机法分为罗浮山组90例、对照组90例。两组均给予改善病情抗风湿药物(DMARDs)等基础治疗,罗浮山组予罗浮山风湿膏药,对照组予罗浮山风湿膏药模拟剂,核心试验疗程4周,继而于其中3家医院进行扩展试验(受试者自愿选择继续接受罗浮山风湿膏药治疗4周)。于治疗前和治疗4、8周后进行评价,腕关节局部症状评价包括疼痛视觉模拟评分(VAS)、腕关节肿胀程度、晨僵持续时间,双腕关节半定量超声评价包括腱鞘炎、滑膜炎、滑膜增生,疾病整体评价包括28处关节活动度评估(DAS28)-C反应蛋白(CRP)评分、健康评定问卷残疾指数(HAQ-DI)、中国类风湿关节炎患者报告的疾病活动度指数(CPRI-RA)、炎性指标红细胞沉降率(ESR)水平,记录试验期间皮肤刺激性评价及不良事件发生情况。有效性评价采用符合方案数据集(PPS)、安全性指标以安全性分析数据集(SS)进行分析。结果在DMARDs等常规用药基础上联合罗浮山风湿膏药治疗4周可改善RA患者VAS评分(P<0.05)、肿胀程度(P<0.05)、晨僵持续时间(P<0.05),超声下腕关节腱鞘炎(P<0.05)、滑膜炎(P<0.05),DAS28-CRP(P<0.05)、HAQ-DI(P<0.05)及CPRI-RA(P<0.05),但与对照组的差异无统计学意义(P>0.05)。治疗8周后,罗浮山组降低VAS评分优于对照组,差异具有统计学意义(P<0.05);可改善超声下腕关节滑膜增生(P<0.05)及ESR水平(P<0.05),但与对照组的差异无统计学意义(P>0.05);两组皮肤刺激性及不良事件发生率的差异无统计学意义(P>0.05)。结论罗浮山风湿膏药治疗RA腕关节炎,止痛效果确切,对超声影像学评价、关节肿胀程度及ESR的改善有优效趋势,安全性高,具有临床长期使用价值。

Objective We aimed to evaluate the clinical efficacy and safety of Luofushan Rheumatic Plaster in the treatment of rheumatoid arthritis(RA)combined with wrist inflammation.Methods A multicenter,block⁃randomized,double⁃blind,placebo⁃controlled clinical trial was conducted including 180 patients with RA combined with wrist tenosynovitis and/or synovitis from eight hospitals who were randomly divided into the Luofushan group(90 cases)and the control group(90 cases).Patients in both groups were given basic treatment such as disease⁃modifying antirheumatic drugs(DMARDs).Patients in the Luofushan group were given Luofushan Rheumatic Plaster,while patients in the control group were given Luofushan Rheumatic Plaster simulant.The core trial duration was 4 weeks,and the extended trial was conducted in three centers(participants could voluntarily choose to continue to receive Luofushan Rheumatic Plaster for an additional 4 weeks).Follow⁃up of local symptoms of the wrist joint(VAS score,swelling degree,duration of morning stiffness),bilateral wrist joint ultrasound(tenosynovitis,synovitis,synovial hyperplasia),overall evaluation of disease(DAS28⁃CRP score,Health Assessment Questionnaire Disability Index[HAQ⁃DI],and Chinese Patient⁃Reported Activity Index with Rheumatoid Arthritis[CPRI⁃RA]),and erythrocyte sedimentation rate(ESR)was conducted one or two times,and skin irritation and adverse events during the experiment were recorded.Effectiveness was analyzed using the per⁃protocol set,and the safety indicators were analyzed using the safety set.Results Compared to pre⁃treatment,adjuvant therapy with Luofushan Rheumatic Plaster for 4 weeks can improve the VAS score(P<0.05),the degree of swelling(P<0.05),morning stiffness duration(P<0.05),wrist tenosynovitis(P<0.05),synovitis(P<0.05),DAS28-CRP(P<0.05),HAQ⁃DI(P<0.05),and CPRI⁃RA(P<0.05),but there were no statistically significant difference compared to the control group.Compared to the control group,pain was alleviated in the Luofushan group after 8 weeks of treatment(P<0.05).Compared to pre⁃treatment adjuvant therapy for 8 weeks can provide additional improvement in the synovial hyperplasia of the wrist joint(P<0.05),and the ESR level(P<0.05),but there were no statistically significant difference compared to the control group.There was no increase in the incidence of skin irritation and adverse events between the two groups(P>0.05).Conclusion Luofushan Rheumatic Plaster has a definite analgesic effect in the treatment of wrist rheumatoid arthritis,and it improves ultrasound imaging result,the degree of joint swelling,and ESR.Moreover,it is safe and suitable for long⁃term clinical use.