Rheumatology B Department, Paris-Descartes University, Cochin Hospital, , Paris, France.
Ann Rheum Dis. 2014 May;73(5):803-9. doi: 10.1136/annrheumdis-2013-204761. Epub 2014 Jan 28.
To assess the 1-year efficacy and safety of a regimen of tocilizumab plus methotrexate or placebo, which was augmented by a treat-to-target strategy from week 24.
ACT-RAY was a double-blind, 3-year trial. Adults with active rheumatoid arthritis despite methotrexate were randomised to add tocilizumab to ongoing methotrexate (add-on strategy) or to switch to tocilizumab plus placebo (switch strategy). Tocilizumab 8 mg/kg was administered every 4 weeks. Conventional open-label disease-modifying antirheumatic drugs (DMARDs) other than methotrexate were added at week 24 or later in patients with DAS28>3.2.
556 patients were randomised; 85% completed 52 weeks. The proportion of patients receiving open-label DMARDs was comparable in the add-on (29%) and switch (33%) arms. Overall, week 24 results were maintained or further improved at week 52 in both arms. Some endpoints favoured the add-on strategy. Mean changes in Genant-modified Sharp scores were small; more add-on (92.8%) than switch patients (86.1%) had no radiographic progression. At week 52, comparable numbers of patients had antidrug antibodies (ADAs; 1.5% and 2.2% of add-on and switch patients, respectively) and neutralising ADAs (0.7% and 1.8%). Rates of serious adverse events and serious infections per 100 patient-year (PY) were 11.3 and 4.5 in add-on and 16.8 and 5.5 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3× upper limit of normal were observed in 11% of add-on and 3% of switch patients.
Despite a trend favouring the add-on strategy, these data suggest that both tocilizumab add-on and switch strategies led to meaningful clinical and radiographic responses.
评估托珠单抗联合甲氨蝶呤或安慰剂方案在第 24 周开始采用靶向治疗策略后的 1 年疗效和安全性。
ACT-RAY 是一项双盲、3 年的试验。尽管正在接受甲氨蝶呤治疗，但仍患有活动性类风湿关节炎的成年人被随机分配至加用托珠单抗联合正在使用的甲氨蝶呤（加用策略）或换用托珠单抗联合安慰剂（换用策略）。托珠单抗 8mg/kg 每 4 周给药 1 次。在 DAS28＞3.2 的患者中，于第 24 周或之后加用除甲氨蝶呤以外的常规开放性疾病修饰抗风湿药物（DMARDs）。
556 名患者被随机分组；85%的患者完成了 52 周的治疗。在加用组（29%）和换用组（33%）中，接受开放性 DMARDs 治疗的患者比例相当。总体而言，在这两个治疗组中，第 24 周的结果在第 52 周时得以维持或进一步改善。一些终点结果更有利于加用策略。改良 Genant Sharp 评分的平均变化较小；更多的加用（92.8%）患者而非换用（86.1%）患者没有影像学进展。在第 52 周时，分别有 1.5%和 2.2%的加用和换用患者出现抗药物抗体（ADA），分别有 0.7%和 1.8%的加用和换用患者出现中和性 ADA。每 100 患者-年（PY）的严重不良事件和严重感染发生率分别为加用组 11.3/100 PY 和 4.5/100 PY，换用组为 16.8/100 PY 和 5.5/100 PY。在基线时丙氨酸氨基转移酶正常的患者中，加用组有 11%和换用组有 3%的患者出现＞3×正常值上限的升高。
尽管加用策略有趋势更优，但这些数据表明，托珠单抗加用和换用策略都能带来有意义的临床和影像学反应。
