重组人白细胞介素-1受体拮抗剂联合甲氨蝶呤对类风湿关节炎病情、影像学影响的临床评价

Clinical Evaluation of the Use of Recombinant Human Interleukin-1 Receptor Antagonist Combines with Methotrexate for the Control the Inflammation of Rheumatoid Arthritis

目的评价重组人白细胞介素-1受体拮抗剂(rhIL-1Ra)治疗活动性类风湿关节炎(RA)的24周疗效及对RA影像学的影响。方法采用多中心、随机、双盲、平行对照的临床试验研究,南方医院试验中心确诊的活动期RA受试者40例,依照方案以3:1比例,随机分为rhIL-1Ra组(治疗组)和MTX组(对照组),治疗组30例予rhIL-1Ra联合MTX治疗,对照组10例予MTX治疗,并进行随访观察,疗程均为24周。主要评价指标为12周和24周时较基线期达到RA疗效评价标准20(ACR20)的患者比例;次要评价指标包括随访12周及24周时较基线期达到RA疗效评价标准50、70(ACR50、ACR70)的患者比例、晨僵持续时间、关节肿胀和关节触痛计数、VAS评分、健康评估问卷(HAQ)、急性期反应物水平(ESR、CRP),并对患者治疗前后的双腕关节进行影像学Sharp评分。结果第12周时治疗组ACR20为73%、ACR50为37%、ACR70为13%,对照组ACR20为10%、ACR50为10%、ACR70为0%(P=0.000);第24周时治疗组ACR20为87%、ACR50为50%、ACR70为37%,对照组ACR20为50%、ACR50为10%、ACR70为0%(P=0.000);其他各项疗效指标也反映出相似的改善程度及趋势(P=0.000)。双腕关节Sharp评分:治疗组0周关节侵蚀评分平均值为2.33,治疗24周为2.23(P=0.795),0周关节狭窄评分的平均值为1.70,治疗24周为1.43(P=0.343);对照组0周关节侵蚀评分平均值为2.60,治疗24周为3.60(P=0.024),0周关节狭窄评分的平均值为1.70,治疗24周为2.50(P=0.019)。结论rhIL-1Ra联合MTX治疗RA24周的疗效明显优于单用MTX,能明显控制RA病程并提示rhIL-1Ra有可能阻止RA患者影像学的进展。

Objective To evaluate the efficacy of using rhIL-1Ra for the treatment of active RA. Methods The study was based on the use of multi-center, randomized, double-blind, parallel-controlled clinical trial research. 40 cases of active RA were obtained from Test Center of Nan-fang hospital. Based on the program 3 ： 1 ratio, the patients were randomly divided into rhIL-1Ra group （treatment group） and the MTX group （control group）. 30 cases of treatment group were treated with rhIL-1Ra combined with MTX; 10 cases of the control group were treated with MTX for 24 weeks. The main evaluation index was the comparison of the proportion of patients reached ACR20 after 12 weeks and 24 weeks to the baseline. The secondary evaluation was the comparison of the proportion of patients reached ACR50, ACR70 after 12 weeks and 24 weeks to the baseline. The index are duration of morning stiffness, joint swelling and joint tenderness count, VAS score, health assessment questionnaire （HAQ）, the level of acute phase reactants （ESR, CRP）, and the sharp score of dual wrist imaging at week 24. Results 30 cases of treatment group treated with rhIL-1Ra plus MTX, 10 cases of the control group to MTX treatment, and follow-up observation, treatment of After the first 12 weeks of treatment the treatment group ACR20 reached 73%, ACR50 37%, and ACR70 13%, while the control group ACR20 reached 10%, ACR50 10%, and ACR70 0% （P= 0.000）; after 24 weeks the treatment group ACR20 reached 87%, ACR50 50%, ACR70 37%, while for the control group ACR20 reached 50%, ACR50 10% and ACR70 0% （P=0.000）. The other indicators also reflects the effect of similar extent and trend of improvement （P= 0.000）. The sharp score of dual wrist joint for （1） the treatment group： the average joint erosion score at week 0 was 2.33 and at week 24 was 2.23 （P=0.795）; the average joint narrow score at week 0 was 1.70 and at 24 weeks was 1.43 （P=0.343）, （2） the control group： the average joint erosion score at week 0 was 2.60 and at 24 weeks was 3.60 （P= 0.024）; the average joints narrow score at week 0 was 1.70 and at 24 weeks was 2.50 （P=0.019）. Conclusion The efficacy of rhIL-1Ra combined with MTX was better than MTX alone. The treatment can significantly control the course of RA and prevent the progress of RA.