From the University of Toronto, Toronto, Ontario; the University of Montreal, Montreal, Quebec, Canada; AbbVie Inc., North Chicago, Illinois; and the University of California San Diego, La Jolla, California, USA.
J Rheumatol. 2014 Feb;41(2):235-43. doi: 10.3899/jrheum.121468. Epub 2013 Dec 1.
Rheumatoid arthritis (RA) treatment recommendations suggest target attainment within the first 3 months of therapy, yet delayed clinical responses can occur. This analysis assessed the longterm clinical, functional, and radiographic outcomes associated with delayed responses to methotrexate (MTX) monotherapy or to the combination of adalimumab (ADA) + MTX.
In this posthoc analysis, patients with early RA who received MTX monotherapy or ADA + MTX in the PREMIER study were categorized based on clinical responses at 3 and 6 months [American College of Rheumatology response, 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP) improvement and targets]. "Month 3" responders met the clinical measure at both months 3 and 6, and "Month 6" responders met the clinical measure only at Month 6. The odds of achieving longterm outcomes [remission (DAS28-CRP < 2.6), normal function (Health Assessment Questionnaire-Disability Index < 0.5), or rapid radiographic progression (Δ modified total Sharp score > 3 U/yr)] were modeled using logistic regression, including treatment, response, and interaction.
A delayed or low-level response was associated with poorer longterm outcomes. Generally, MTX Month 6 responders demonstrated worse clinical, functional, and radiographic outcomes than Month 3 MTX and Month 3 or 6 ADA + MTX responders. Although similar longterm benefit was observed for ADA + MTX responders, delayed (Month 6) responders exhibited downward trends in clinical, functional, and radiographic outcomes that were comparable with those experienced by Month 3 MTX responders.
Response speed and magnitude predict longterm outcomes in patients with early RA treated with MTX or ADA + MTX. MTX-treated patients failing to demonstrate a Month 3 clinical response have less-favorable outcomes than other groups, while outcomes in ADA + MTX Month 3 and Month 6 responders tended to be comparable.
类风湿关节炎（RA）治疗建议表明，在治疗的前 3 个月内应达到治疗目标，但可能出现延迟的临床应答。本分析评估了与甲氨蝶呤（MTX）单药治疗或阿达木单抗（ADA）+MTX 联合治疗的延迟应答相关的长期临床、功能和放射学结局。
在这项事后分析中，根据 PREMIER 研究中接受 MTX 单药或 ADA+MTX 治疗的早期 RA 患者在 3 个月和 6 个月时的临床应答情况进行分类[美国风湿病学会应答，28 关节疾病活动评分（DAS28）-C 反应蛋白（CRP）改善和目标]。“第 3 个月”应答者在第 3 个月和第 6 个月均符合临床指标，“第 6 个月”应答者仅在第 6 个月符合临床指标。使用逻辑回归模型对长期结局[缓解（DAS28-CRP<2.6）、正常功能（健康评估问卷残疾指数<0.5）或快速放射学进展（Δ改良总Sharp 评分>3 个单位/年）]的可能性进行建模，包括治疗、应答和相互作用。
延迟或低水平应答与较差的长期结局相关。通常，MTX 第 6 个月应答者的临床、功能和放射学结局较 MTX 第 3 个月和第 3 个月或第 6 个月 ADA+MTX 应答者差。尽管 ADA+MTX 应答者观察到相似的长期获益，但延迟（第 6 个月）应答者的临床、功能和放射学结局呈下降趋势，与 MTX 第 3 个月应答者的相似。
在接受 MTX 或 ADA+MTX 治疗的早期 RA 患者中，应答速度和幅度可预测长期结局。未能在第 3 个月显示临床应答的 MTX 治疗患者的结局较其他组差，而 ADA+MTX 第 3 个月和第 6 个月应答者的结局趋于相似。
