UCSD, UCSD, Rheumatology, Allergy, Immunology, La Jolla, CA, USA.
Ann Rheum Dis. 2013 Jan;72(1):64-71. doi: 10.1136/annrheumdis-2011-201247. Epub 2012 May 5.
To assess the efficacy and safety of adalimumab plus methotrexate (ADA+MTX) compared with methotrexate monotherapy in achieving stable low disease activity (LDA; disease activity score (DAS28(CRP)) <3.2 at weeks 22 and 26) and clinical, radiographic and functional outcomes in methotrexate-naive patients with early rheumatoid arthritis (RA).
1032 patients with active RA were randomly assigned 1:1 to ADA+MTX or placebo plus methotrexate (PBO+MTX) for 26 weeks. Treatment modifications were to be made in a subsequent study period based on the achievement of DAS28(CRP) <3.2 at weeks 22 and 26. Post-hoc analyses compared patients achieving stable remission using DAS28 and 2010 ACR/EULAR criteria with those achieving LDA but not remission.
Among patients completing 6 months, 44% (207/466) ADA+MTX versus 24% (112/460) PBO+MTX patients achieved stable LDA at weeks 22 and 26 (p<0.001). Combination therapy was statistically superior to methotrexate in obtaining higher ACR20/50/70 responses, more clinical remissions, greater mean reductions in DAS28(CRP), no radiographic progression, and normal functional status at week 26 (p<0.001 for all). The only factor predicting stable LDA was disease activity at week 12. Patients achieving ACR/EULAR remission, particularly in the PBO+MTX group, had some advantage in radiographic outcomes compared with patients who only achieved LDA (but not remission). The overall frequency of adverse events was comparable between groups. There were more serious infections and deaths in the ADA+MTX group, with a possible age effect.
Treatment with ADA+MTX was significantly superior to methotrexate alone with respect to clinical, radiographic and functional outcomes in patients with early active RA. Before initiating treatment with adalimumab, individual patient evaluation of the benefit/risk ratio should be carefully considered.
评估阿达木单抗联合甲氨蝶呤（ADA+MTX）与甲氨蝶呤单药治疗在实现早期类风湿关节炎（RA）患者病情稳定的低疾病活动度（LDA；第 22 周和第 26 周时疾病活动评分（DAS28（CRP））<3.2）以及临床、放射学和功能结局方面的疗效和安全性，这些患者此前未曾接受过甲氨蝶呤治疗。
1032 例活动性 RA 患者以 1:1 的比例随机分配至 ADA+MTX 或安慰剂联合甲氨蝶呤（PBO+MTX）组，治疗 26 周。根据第 22 周和第 26 周时 DAS28（CRP）<3.2 的达标情况，在后续研究期间对治疗方案进行调整。事后分析比较了根据 DAS28 和 2010 ACR/EULAR 标准达到缓解的患者与达到 LDA 但未缓解的患者。
在完成 6 个月治疗的患者中，ADA+MTX 组有 44%（207/466）达到了第 22 周和第 26 周的稳定 LDA，而 PBO+MTX 组为 24%（112/460）（p<0.001）。与甲氨蝶呤相比，联合治疗在获得更高的 ACR20/50/70 反应、更多的临床缓解、DAS28（CRP）更大的平均降低、无放射学进展以及第 26 周时正常的功能状态方面具有统计学优势（所有 p<0.001）。唯一能预测稳定 LDA 的因素是第 12 周时的疾病活动度。与仅达到 LDA（而非缓解）的患者相比，达到 ACR/EULAR 缓解的患者（尤其是在 PBO+MTX 组）在放射学结局方面具有一定优势。两组之间不良事件的总体发生率相当。ADA+MTX 组的严重感染和死亡事件更多，可能存在年龄效应。
与甲氨蝶呤单药治疗相比，ADA+MTX 治疗在早期活动性 RA 患者的临床、放射学和功能结局方面具有显著优势。在开始使用阿达木单抗治疗之前，应仔细考虑患者个体的获益/风险比。
