甲氨蝶呤联合小剂量泼尼松治疗类风湿关节炎的短期疗效与安全性

The short-term efficacy and safety of methotrexate plus low dose prednisone in patients with rheumatoid arthritis

目的从“目标治疗”的角度，初步评价甲氨蝶呤联合小剂量糖皮质激素（简称激素）治疗类风湿关节炎（RA）的疗效与安全性。方法入组患者均符合2010年美国风湿病学会（ACR）和欧洲抗风湿病联盟（EULAR）制定的RA分类标准，所有患者均口服甲氨蝶呤15mg／周、叶酸5mg／周和泼尼松（≤10mg／d），于第0、4、12周记录患者疾病活动度和疗效，主要评价指标：基于C反应蛋白（CRP）计算的28个关节疾病活动指数（DAS28）；次要评价指标：EULAR疗效标准，达到ACR制定的RA疗效缓解20％（ACR20）、RA疗效缓解50％（ACR50）、RA疗效缓解70％（ACR70）的比例，简化疾病活动指数（SDAI）和临床疾病活动指数（CDAI）。于治疗第4、12周记录甲氨蝶呤相关不良反应，第12周记录泼尼松相关不良反应。结果共入选RA患者76例，完成4周、12周治疗者分别有68例、65例。治疗第12周时，达到DAS28缓解、低疾病活动度和中高疾病活动度者分别为30例（46．2％）、9例（13．8％）、26例（40．0％）。治疗后达到低疾病活动度的9例患者中3例为早期RA或中病程患者（病程≤2年），未达目标治疗要求，36例（55．4％）患者治疗达标；达到EULAR较好疗效标准及ACR20、ACR50、ACR70的比例分别为29．2％、75．4％、69．2％、64．6％；SDAI、CDAI达标比例分别为76．9％、58．5％。治疗第4周甲氨蝶呤相关不良反应发生率：肝功能异常11．8％、腹痛4．4％、腹胀反酸4．4％、恶心2．9％；第12周甲氨蝶呤相关不良反应发生率：腹胀反酸4．6％，腹痛、恶心、脱发、带状疱疹病毒感染、肺部感染均为1．5％；未见严重不良反应。结论基于“目标治疗”的理念及药物疗效和安全性的考虑，甲氨蝶呤联合小剂量泼尼松仍不失为当前治疗RA的有效手段之一。

Objective To evaluate the clinical efficacy and safety of methotrexate （MTX）plus low dose glucoeorticoid in the treatment of rheumatoid arthritis （RA） from the ＂ target control＂ point of view. Methods Patients diagnosed as RA according to American College of Rheumatology （ACR）/European League against Rheumatism （EULAR） 2010 classification criteria were enrolled. All of the patients were prescribed with 15 mg/week MTX, 5 mg/week folic acid and prednisone （not exceeding 10 mg/day） orally. At week 0, 4, 12, disease activity and clinical efficacy were recorded. Co-primary assessment criterion was disease activityscore （DAS28）-based on C-reactive protein （CRP）. Secondary assessment criteria included EULAR response criteria, ACR response criteria, simplified disease activity index（SDAI） , clinical disease activity index（CDAI）. The tolerability and toxicity of MTX was recorded at week 4, 12. All patients were evaluated for the occurrence of adverse drug reactions associated with prednisone at week 12. Results A total of 76 patients were enrolled in the study. At week 4 and 12, 68 and 65 patients completed regular follow-up respectively. At week 12, there were 30（46. 2% ）, 9（ 13.8% ）, 26（40. 0% ） patients who met DAS28-CRP remission, low disease activity, middle and high disease activity criterion respectively. Three of nine patients who grouped in low disease activity after therapy were early or intermediate patients and didn＇t reach the target. Thus 36 （55.4%） patients met the standard of target control. The percentage of patients who met the criteria of EULAR good response, the ACR criteria for 20% improvement （ACR20） , the ACR criteria for 50% improvement （ACR50） , the ACR criteria for 70% improvement （ACR70） were 29. 2% , 75. 4%, 69. 2%, 64. 6%, respectively. The proportion of patients meeting the standard of treat to target using SDAI and CDAI were 76. 9%, 58.5% respectively. The rate of liver injury, abdominal pain, abdominal distention and acid reflux, nausea were 11.8%, 4. 4% , 4. 4% , 2. 9% respectively at week 4. At week 12, 4. 6% of patients reported abdominal distention. There was only one patient （ 1.5% ） each who complained of abdominal pain, nausea, loss of hair, variceUa zoster virus infection and pulmonary infection at week 12. No serious adverse event was observed during the study. Conclusions Based on the view of ＂target control, drug efficacy and safety, MTX plus low dose prednisone is still a useful therapeutic regimen for RA at present.