Department of Rheumatology, Instituto de Investigación Hospital 12 de Octubre, Universidad Complutense de Madrid, Spain.
Department of Rheumatology, Hospital Universitario Virgen Macarena, Sevilla, Spain.
Clin Exp Rheumatol. 2019 May-Jun;37(3):437-444. Epub 2018 Sep 17.
The aim of the JUST-ACT study was to assess whether the add-on effect of tocilizumab (TCZ) to background methotrexate (MTX) observed in MTX-inadequate responders with active rheumatoid arthritis (RA), would be sustained when MTX is withdrawn.
A double-blind, parallel-group, phase 3 study in biologic-naïve RA patients with a disease activity score 28 (DAS28)>3.2 despite MTX which were treated with TCZ+MTX for an initial 16-week period. Patients who at week 16 achieved low disease activity (LDA) (DAS28≤3.2) were randomised to continue with TCZ+MTX or switch to TCZ + placebo (PBO) for an additional 12 weeks. The primary endpoint was the change in DAS28-ESR from the randomisation at week 16 to week 28. Non-inferiority was confirmed if the upper limit of the two-sided 95%CI for the treatment difference between TCZ+MTX and TCZ monotherapy groups was lower than the selected non-inferiority margin of 0.6.
261 patients completed the first 16 weeks of TCZ+MTX treatment and 165 were randomised (83 to TCZ+MTX and 82 to TCZ+PBO). For the primary endpoint, the adjusted treatment difference (95% CI) in mean change of DAS28-ESR was -0.06 (-0.40 to 0.27), and therefore the non-inferiority of switching to TCZ monotherapy versus continuing with TCZ+MTX was demonstrated. In both treatment groups, the percentage of patients in clinical remission from 16 to 28 weeks was similar as were the improvements in disease activity, functional disability and quality of life.
In MTX non-responder patients achieving LDA with TCZ+MTX, switching to TCZ monotherapy is non-inferior to continuing the combination.
JUST-ACT 研究的目的是评估在接受甲氨蝶呤（MTX）治疗但应答不足的活动期类风湿关节炎（RA）患者中，托珠单抗（TCZ）添加到 MTX 后的附加疗效是否可持续，当 MTX 被停用后。
这项在生物初治的 RA 患者中开展的、双盲、平行分组、3 期研究中，患者的疾病活动评分 28（DAS28）＞3.2，且 MTX 应答不足，他们接受 TCZ+MTX 治疗 16 周的初始治疗期。在第 16 周时达到低疾病活动（LDA）（DAS28≤3.2）的患者被随机分为继续 TCZ+MTX 治疗或转为 TCZ+安慰剂（PBO）治疗 12 周。主要终点是从第 16 周随机分组到第 28 周时的 DAS28-ESR 变化。如果 TCZ+MTX 组与 TCZ 单药组之间治疗差异的双侧 95%CI 的上限低于选择的 0.6 非劣效性边界，则确认非劣效性。
261 例患者完成了 TCZ+MTX 治疗的前 16 周，其中 165 例患者被随机分组（83 例接受 TCZ+MTX，82 例接受 TCZ+PBO）。对于主要终点，DAS28-ESR 均值变化的调整治疗差异（95%CI）为-0.06（-0.40 至 0.27），因此证实了转换为 TCZ 单药治疗与继续 TCZ+MTX 治疗的非劣效性。在这两个治疗组中，从第 16 周到第 28 周时达到临床缓解的患者比例相似，疾病活动度、功能残疾和生活质量的改善也相似。
在接受 TCZ+MTX 治疗后达到 LDA 的 MTX 应答不足的患者中，转换为 TCZ 单药治疗与继续联合治疗相比是非劣效的。
