l'Ami Merel J, Kneepkens Eva L, Nurmohamed Michael T, Krieckaert Charlotte L M, Visman Ingrid M, Wolbink Gert-Jan
Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands.
Amsterdam Rheumatology and Immunology Center, Reade; and Amsterdam Rheumatology and immunology Center, VU University Medical Center, Amsterdam, The Netherlands.
Clin Exp Rheumatol. 2017 May-Jun;35(3):431-437. Epub 2017 Jan 5.
To observe long-term clinical response and drug survival in a prospective two-year cohort study in rheumatoid arthritis (RA) patients starting adalimumab or etanercept treatment, with or without methotrexate (MTX), after failure of conventional DMARD therapy, including MTX.
Disease activity score of 28 joints (DAS28) and Health Assessment Questionnaire (HAQ) were collected of 873 consecutive RA patients, treated with adalimumab or etanercept, prospectively at baseline, 4, 16, 28, 40, 52, 78 and 104 weeks of biological therapy. Sustained minimal disease activity (MDA), DAS28 <2.6 for at least 24 consecutive weeks, biological discontinuation, ΔHAQ and ΔDAS28 were compared between patients treated with or without concomitant MTX for etanercept and adalimumab separately.
More patients treated with adalimumab and MTX (42%) achieved sustained MDA than patients without MTX (18%). The hazard ratio (HR) was 2.3 [1.4-3.9]. No significant difference was found in etanercept treatment (with MTX 33% vs. 28% without MTX), HR 1.1 [0.8-1.6]. More patients treated without MTX discontinued treatment than patients with MTX co-treatment in adalimumab (HR 2.1 [1.5-3.0]) and etanercept (HR 1.9 [1.0-3.4]). The mean decrease in DAS28 over time was higher for patients treated with MTX in adalimumab (regression coefficient (RC): 0.57, p<0.001), but was not significantly different in etanercept treatment (RC 0.05, p=0.427). No significant differences were found in ΔHAQ.
Treatment discontinuation is lower in patients treated with MTX in both adalimumab and etanercept treatment. However, considering good clinical response, in contrast to etanercept, a synergetic effect of MTX is observed only in adalimumab treatment.
在一项前瞻性为期两年的队列研究中，观察类风湿关节炎（RA）患者在包括甲氨蝶呤（MTX）在内的传统改善病情抗风湿药（DMARD）治疗失败后，开始使用阿达木单抗或依那西普治疗（联合或不联合MTX）的长期临床反应和药物生存期。
前瞻性收集了873例连续接受阿达木单抗或依那西普治疗的RA患者在生物治疗基线、第4、16、28、40、52、78和104周时的28个关节疾病活动评分（DAS28）和健康评估问卷（HAQ）。分别比较了依那西普和阿达木单抗治疗中联合或不联合MTX患者的持续最小疾病活动度（MDA，DAS28连续至少24周<2.6）、生物制剂停药情况、ΔHAQ和ΔDAS28。
与未使用MTX的患者（18%）相比，更多接受阿达木单抗联合MTX治疗的患者（42%）达到了持续MDA。风险比（HR）为2.3[1.4 - 3.9]。依那西普治疗组未发现显著差异（联合MTX为33%，未联合MTX为28%），HR为1.1[0.8 - 1.6]。在阿达木单抗（HR 2.1[1.5 - 3.0]）和依那西普（HR 1.9[1.0 - 3.4]）治疗中，未使用MTX的患者比联合MTX治疗的患者停药更多。在阿达木单抗治疗中，联合MTX患者随时间的DAS28平均下降幅度更大（回归系数（RC）：0.57，p<0.001），但在依那西普治疗中无显著差异（RC 0.05，p = 0.427）。ΔHAQ未发现显著差异。
在阿达木单抗和依那西普治疗中，联合MTX治疗的患者停药率较低。然而，考虑到良好的临床反应，与依那西普不同，仅在阿达木单抗治疗中观察到MTX的协同作用。
