Alfaro-Lara Roberto, Espinosa-Ortega Hector Fabricio, Arce-Salinas César Alejandro
Staff member, Hospital Central Sur Pemex, Mexico.
Assistant professor, Rheumatology consultant, Staff member, Hospital Central Sur Pemex, Mexico.
Reumatol Clin (Engl Ed). 2019 May-Jun;15(3):133-139. doi: 10.1016/j.reuma.2017.07.020. Epub 2017 Sep 1.
To assess the efficacy and side effects of methotrexate and leflunomide in patients with rheumatoid arthritis (RA) as the first disease-modifying antirheumatic drug (DMARD).
We performed a systematic review and meta-analysis of clinical studies that included patients who took methotrexate, leflunomide, placebo or another DMARD for RA treatment. A systematic review yielded 1971 articles from databases; once completely reviewed, 73 trials that completed inclusion criteria were selected. In structured workshops for discussion and assessment of each article, 6 could be meta-analyzed for the primary and secondary outcomes: achievement of American College of Rheumatology (ACR) 20 and its core set components; and change of serum C-reactive protein (CRP) levels, Health Assessment Questionnaire Disability Index (HAQ-Di), liver enzyme aspartate transaminase/alanine transaminase ratio, new gastrointestinal (GI) side effects and infections.
A total of 1984 patients were included: 986 took leflunomide and 998 methotrexate. The probability of achieving ACR 20 had an odds ratio (OR) of 0.88 (95% confidence interval [CI] 0.74, 1.06) with a trend toward favoring methotrexate; reduction of the swollen joint count was greater for methotrexate: mean difference=0.82 (95%CI 0.24, 1.39); tender joint count, physician global assessment, HAQ-Di, and serum CRP levels revealed no significant difference between groups. Increased liver enzymes were more frequent in the leflunomide group, OR=0.38 (95%CI 0.27, 0.53), and new GI complaints were more common with methotrexate (OR=1.44; 95%CI 1.17, 1.79). There was no difference in the incidence of non-severe infections.
Leflunomide used as the first DMARD in RA seemed to be as efficacious as methotrexate; only the reduction of swollen joint count was more marked for methotrexate. Leflunomide was linked to a greater increase in liver enzymes, but there were fewer GI complaints.
评估甲氨蝶呤和来氟米特作为类风湿关节炎（RA）患者的首种改善病情抗风湿药（DMARD）的疗效及副作用。
我们对临床研究进行了系统评价和荟萃分析，这些研究纳入了接受甲氨蝶呤、来氟米特、安慰剂或其他DMARD治疗RA的患者。系统评价从数据库中检索到1971篇文章；经全面审查后，选择了73项符合纳入标准的试验。在用于讨论和评估每篇文章的结构化研讨会上，6项试验可针对主要和次要结局进行荟萃分析：达到美国风湿病学会（ACR）20及其核心指标；血清C反应蛋白（CRP）水平、健康评估问卷残疾指数（HAQ-Di）、肝酶天冬氨酸转氨酶/丙氨酸转氨酶比值的变化、新出现的胃肠道（GI）副作用和感染情况。
共纳入1984例患者：986例服用来氟米特，998例服用甲氨蝶呤。达到ACR 20的概率的比值比（OR）为0.88（95%置信区间[CI] 0.74，1.06），有倾向于甲氨蝶呤的趋势；甲氨蝶呤使肿胀关节计数减少更明显：平均差值=0.82（95%CI 0.24，1.39）；压痛关节计数、医生整体评估、HAQ-Di和血清CRP水平在两组间无显著差异。来氟米特组肝酶升高更常见，OR=0.38（95%CI 0.27，0.53），而甲氨蝶呤导致的新的胃肠道不适更常见（OR=1.44；95%CI 1.17，1.79）。非严重感染的发生率无差异。
来氟米特作为RA患者的首种DMARD似乎与甲氨蝶呤疗效相当；仅甲氨蝶呤使肿胀关节计数减少更显著。来氟米特与肝酶升高幅度更大有关，但胃肠道不适较少。
