From *CAICI Instituto, Rosario, Santa Fe, Argentina; †IDEARG and ‡Saludcoop Clínica, Bogotá, Colombia; §Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; ∥BIOCEM and ¶Universidad Marista de Mérida, Mérida, Yucatán, Mexico; #Pfizer Inc and**Formerly of Pfizer Inc, Collegeville, PA.
J Clin Rheumatol. 2014 Jan;20(1):25-33. doi: 10.1097/RHU.0000000000000055.
Previous global studies examined etanercept (ETN) + methotrexate (MTX) for treatment of rheumatoid arthritis (RA), but included few subjects from Latin America.
The objective of this study was to compare the safety and efficacy of ETN + MTX versus a standard-of-care disease-modifying antirheumatic drug (DMARD) + MTX in Latin American subjects with moderate to severe active RA despite MTX therapy.
This open-label, active-comparator study (NCT00848354) randomized subjects 2:1 to ETN 50 mg/wk + MTX or investigator-selected DMARD (sulfasalazine or hydroxychloroquine) + MTX (ETN + MTX, n = 281; DMARD + MTX, n = 142). The primary end point was the proportion achieving American College of Rheumatology (ACR) 50 at week 24. Secondary end points included ACR20/70, disease activity score (DAS) 28 measures, and mean change in modified total Sharp score. Patient-reported outcomes were the Health Assessment Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale, Work Productivity and Activity Impairment: RA (WPAI:RA), and Caregiver Burden and Resource Utilization. Statistical analyses were stratified by country; χ test and analysis of covariance were used. Adverse events were monitored.
More subjects achieved ACR50 at week 24 with ETN + MTX versus DMARD + MTX (62% vs 23%, respectively), in addition to secondary end points (P < 0.0001 for all); mean change in modified total Sharp score was lower for the ETN + MTX group (0.4 vs 1.4, respectively; P = 0.0270). Improvements in patient-reported outcomes favored ETN + MTX for Health Assessment Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale for depression, WPAI:RA, and Caregiver Burden and Resource Utilization emergency department visits for RA (P < 0.01). Overall, adverse events were similar between the groups (69% vs 68%,); serious adverse events were also similar (4% vs 1%). The rate of overall infections was higher with ETN + MTX (38%) than DMARD + MTX (22%, P ≤ 0.001).
Consistent with published global data among RA patients with inadequate response to MTX, adding ETN to MTX demonstrated better efficacy than adding one other conventional DMARD to MTX. No new safety issues were observed. ETN + MTX provided favorable benefit-risk profile among RA patients from LA region.
先前的全球研究考察了依那西普（ETN）+甲氨蝶呤（MTX）治疗类风湿关节炎（RA）的效果，但纳入的来自拉丁美洲的受试者较少。
本研究旨在比较 ETN+MTX 与标准治疗的疾病修饰抗风湿药物（DMARD）+MTX 在接受 MTX 治疗但病情仍处于活动期的中重度 RA 拉丁美洲受试者中的安全性和疗效。
这是一项开放标签、活性对照研究（NCT00848354），将受试者按 2:1 的比例随机分配至 ETN 50mg/周+MTX 或研究者选择的 DMARD（柳氮磺胺吡啶或羟氯喹）+MTX（ETN+MTX 组，n=281；DMARD+MTX 组，n=142）。主要终点为第 24 周时达到美国风湿病学会（ACR）50 的比例。次要终点包括 ACR20/70、疾病活动评分（DAS）28 测量值和改良总 Sharp 评分的平均变化。患者报告的结果为健康评估问卷（HAQ）、36 项简短健康调查量表（SF-36）、医院焦虑和抑郁量表（HADS）、工作生产力和活动障碍：类风湿关节炎（WPAI:RA）以及照顾者负担和资源利用。统计分析按国家分层；χ检验和协方差分析。监测不良事件。
与 DMARD+MTX 相比，更多的 ETN+MTX 组受试者在第 24 周时达到 ACR50（分别为 62%和 23%），次要终点也如此（所有 P<0.0001）；ETN+MTX 组改良总 Sharp 评分的平均变化较低（分别为 0.4 和 1.4，P=0.0270）。在患者报告的结果中，HAQ、SF-36、HADS 抑郁部分、WPAI:RA 和照顾者负担和资源利用 RA 急诊就诊，ETN+MTX 组的改善情况均优于 DMARD+MTX 组（均 P<0.01）。总体而言，两组的不良事件发生率相似（分别为 69%和 68%）；严重不良事件也相似（分别为 4%和 1%）。ETN+MTX 组的总感染率（38%）高于 DMARD+MTX 组（22%，P≤0.001）。
与 MTX 治疗反应不足的 RA 全球数据一致，与 MTX 联合应用 ETN 比联合应用另一种常规 DMARD 更有效。未观察到新的安全性问题。ETN+MTX 为来自拉丁美洲地区的 RA 患者提供了有利的风险获益状况。
