来源：风湿病与关节炎,2019,8（2）:21-26.

甲氨蝶呤治疗类风湿关节炎的时间治疗学临床研究（临床研究）

王志强，张晓刚，马　旭，张明明，刘彦卿，李振彬

　　【摘　要】目的：通过观察甲氨蝶呤不同时间给药对类风湿关节炎临床疗效的影响，确定甲氨蝶呤的最佳用药时间，为临床治疗提供依据。方法：将62例类风湿关节炎患者随机分为甲氨蝶呤8∶00组和甲氨蝶呤20∶00组，每组31例。2组患者分别于相应时间给予甲氨蝶呤治疗，其他治疗相同，均连续治疗12周。分别于治疗4，8，12周访视，对临床和实验室指标进行评价。记录治疗过程中出现的所有不良反应。结果：2组各30例完成研究。2组治疗8，12周的DAS28-ESR均较各组基线明显降低，差异有统计学意义（P < 0.01）。甲氨蝶呤20∶00组治疗12周的DAS28-ESR明显低于甲氨蝶呤8∶00组，差异有统计学意义（P < 0.05）。治疗4，8，12周时甲氨蝶呤20∶00组达到ACR20、ACR50、ACR70的患者比例均高于同期甲氨蝶呤8∶00组，但仅12周达到ACR50的患者比较，差异有统计学意义（P < 0.05）。2组各项临床和实验室指标随时间延长均有改善，但各时间点2组间比较，差异均无统计学意义（P > 0.05）。2组均未发生严重不良事件，不良事件总体发生率比较，差异无统计学意义（P > 0.05）；但甲氨蝶呤20∶00组胃肠道反应发生率显著低于甲氨蝶呤8∶00组（P < 0.05）。结论：甲氨蝶呤不同时间给药治疗类风湿关节炎疗效存在差异，20∶00给药可能更有效控制类风湿关节炎患者疾病活动，需进一步研究确认。

　　【关键词】　关节炎，类风湿；甲氨蝶呤；时间治疗学；临床研究

Clinical Research on Methotrexate Chronotherapy in Rheumatoid Arthritis

WANG Zhi-qiang,ZHANG Xiao-gang,MA Xu,ZHANG Ming-ming,LIU Yan-qing,LI Zhen-bin

　　【ABSTRACT】Objective:To investigate the effect of methotrexate by different administration times on the outcomes of rheumatoid arthritis,and to determine the best time to use methotrexate in order to provide the basis for clinical treatment.Methods:Sixty-two patients with rheumatoid arthritis were randomly divided into methotrexate 8∶00 group and methotrexate 20∶00 group,31 cases in each group.Two groups of patients were given methotrexate treatment at the corresponding time point,the other treatments were the same,both of them for 12 weeks.Clinical evaluations and laboratory index detection were performed at 4,8,12 weeks of treatment.Adverse events were recorded during therapy.Results:There were 30 cases to complete the study in each group separately.The DAS28-ESR of 8,12 weeks of treatment was significantly lower than that of baseline in both groups（P < 0.01）.The difference of the DAS28-ESR between two groups was remarkable after 12 weeks treatment.At 4,8,12 weeks of treatment,the numbers of patients reaching ACR20,ACR50 and ACR70 in methotrexate 20∶00 group were higher than those in methotrexate 8∶00 group at the same times,but only statistically significant difference of ACR50 at 12 weeks was found（P < 0.05）.The clinical and laboratory indexes of the two groups were improved with the extension of time,but there was no significant difference between the two groups at each time point（P < 0.05）.The adverse events were mild in both groups,the incidence of gastrointestinal discomfort in the methotrexate 20∶00 group was significantly lower than that in the methotrexate 8∶00 group（P < 0.05）.Conclusion:The efficacy of methotrexate administration at different times in the treatment of rheumatoid arthritis is different.Methotrexate administration at 20∶00 may be more effective in controlling disease activity in patients with rheumatoid arthritis,which needs further study to confirm.

　　【Keywords】 arthritis,rheumatoid;methotrexate;chronotherapy;clinical study