甲氨蝶呤周期联合小剂量环磷酰胺治疗类风湿关节炎的疗效及安全性评估

摘要

目的：评价甲氨蝶呤（MTX）周期联合小剂量环磷酰胺（CTX）治疗类风湿关节炎（RA）患者的疗效及安全性。方法将所纳入的RA患者采用随机数字表法分为单用MTX组、单用CTX组及MTX联合CTX治疗组。在基线和24周时对患者进行疗效及安全性评估。以美国风湿病学会（ACR）疗效评价指标ACR20为主要疗效指标，ACR50、ACR70、欧洲抗风湿联盟（EULAR）疗效指标、DAS28评分、疼痛目视模拟测试表（VAS）评分、患者对自身健康状况的总体评估（PGA）、医生总体评价、压痛关节数（TJC）、压痛关节指数（TJI）、肿胀关节数（SJC）、肿胀关节指数（SJI）、健康评估问卷（HAQ）为次要疗效指标。结果治疗24周后，MTX＋CTX组达ACR20改善的患者比例（81％）高于MTX组（56％）及CTX组（35％），差异有统计学意义（P＜0．05或P＜0．01）。24周时MTX＋CTX组达ACR50改善的患者比例高于CTX组（P＜0．05），与MTX组之间差异未达到统计学意义（P＞0．05）。在第24周，MTX＋CTX组达到EULAR有效的患者比例（77％）高于MTX组（48％）及CTX组（35％），差异有统计学意义（P＜0．05或P＜0．01）。各组DAS28分数均较基线下降（P＜0．05），24周时MTX＋CTX组DAS28分数低于MTX组和CTX组（P＜0．05）。24周时MTX＋CTX组在压痛关节数/指数、疼痛VAS评分、ESR的改善程度高于MTX组（P＜0．05），在压痛关节数/指数、肿胀关节数/指数、疼痛VAS评分、PGA、医生总体评价、HAQ、ESR的改善程度高于CTX组（P＜0．05）。3组之间不良反应发生率差异无统计学意义。结论 MTX联合CTX治疗能显著改善RA患者的症状、体征和实验室炎性指标，疗效优于单用MTX及单用CTX，两者联合治疗安全耐受性好，与单用MTX及单用CTX相比，并不增加不良反应的发生率。%Objective To evaluate the effect and safety of methotrexate (MTX) and low-dose cyclophosphamide (CTX) in patients with rheumatoid arthritis (RA). Methods All included RA patients were randomly divided into the MTX alone, CTX alone, and MTX plus CTX treatment groups. The effect and safety of MTX alone, CTX alone, and MTX plus CTX at the baseline and 24 weeks in all patients were evaluated. The primary parameter was based on the American College of Rheumatology 20 (ACR20) criteria. The secondary parameters were based on the ACR50, ACR70 and the European League against Rheumatism (EULAR) criteria, DAS28 score, pain visual analogue scale (VAS) score, self-assessment of general health for patients, general assessment by physicians, tender joint count (TJC), joint tenderness index (TJI), swollen joint count (SJC), swollen joints index (SJI), and health assessment questionnaire (HAQ). Results At 24 weeks after the treatment, the proportion of patients reached to ACR20 improvement in the MTX+CTX group (81%) was higher than that in the MTX group (56%) and CTX group (35%), and the difference was statistically significant (P0.05). At 24 weeks, the proportion of patients reached to effec-tive EULAR criteria in the MTX+CTX group (77%) was higher than that in the MTX group (48%) and CTX group (35%), and the difference was statistically significant (P<0.05 or P<0.01). The DAS28 score in each group was de-creased compared with that at the baseline (P<0.05). At 24 weeks, the DAS28 score in the MTX+CTX group was low-er than that in the MTX group and CTX group (P<0.05). At 24 weeks, the improvement of TJC/TJI, pain VAS score and ESR in the MTX+CTX group was higher than that in the MTX group (P<0.05); and the improvement of TJC/TJI, SJC/SJI, pain VAS score, self-assessment of general health for patients, general assessment by physicians, HAQ and ESR in the MTX+CTX group was higher than that in the MTX group (P<0.05). There was no statistically significant difference in the incidence of adverse reactions among the three groups. Conclusion MTX and CTX can significantly improve the symptoms, signs and laboratory inflammatory markers in RA patients. The effect of MTX and CTX is bet-ter than that of using MTX or CTX alone, which is safe, well tolerated, without increasing the inicidence of adverse re-actions.