Huizinga T W J, Conaghan Philip G, Martin-Mola Emilio, Schett Georg, Amital Howard, Xavier Ricardo M, Troum Orrin, Aassi Maher, Bernasconi Corrado, Dougados Maxime
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Ann Rheum Dis. 2015 Jan;74(1):35-43. doi: 10.1136/annrheumdis-2014-205752. Epub 2014 Aug 28.
To assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission.
ACT-RAY was a double-blind 3-year trial. Patients with active rheumatoid arthritis despite MTX were randomised to add TCZ to ongoing MTX (add-on strategy) or switch to TCZ plus PBO (switch strategy). Using a treat-to-target approach, open-label conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), other than MTX, were added from week 24 if Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) >3.2. Between weeks 52 and 104, patients in sustained clinical remission (DAS28-ESR <2.6 at two consecutive visits 12 weeks apart) discontinued TCZ and were assessed every 4 weeks for 1 year. If sustained remission was maintained, added csDMARDs, then MTX/PBO, were discontinued.
Of the 556 randomised patients, 76% completed year 2. Of patients entering year 2, 50.4% discontinued TCZ after achieving sustained remission and 5.9% achieved drug-free remission. Most patients who discontinued TCZ (84.0%) had a subsequent flare, but responded well to TCZ reintroduction. Despite many patients temporarily stopping TCZ, radiographic progression was minimal, with differences favouring add-on treatment. Rates of serious adverse events and serious infections per 100 patient-years were 12.2 and 4.4 in add-on and 15.0 and 3.7 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3×upper limit of normal were more frequent in add-on (14.3%) versus switch patients (5.4%).
Treat-to-target strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for about 3 months, but most patients eventually flared. TCZ restart led to rapid improvement.
NCT00810199.
评估托珠单抗（TCZ）联合甲氨蝶呤/安慰剂（MTX/PBO）治疗2年的疗效和安全性，以及因持续缓解而停用TCZ的患者的疾病活动过程。
ACT-RAY是一项为期3年的双盲试验。尽管使用了MTX，但仍患有活动性类风湿性关节炎的患者被随机分为在持续使用MTX的基础上加用TCZ（加用策略）或改用TCZ加PBO（转换策略）。采用达标治疗方法，如果基于红细胞沉降率的28个关节疾病活动评分（DAS28-ESR）>3.2，则从第24周开始加用除MTX以外的开放标签传统合成改善病情抗风湿药（csDMARDs）。在第52周至104周之间，持续临床缓解（在相隔12周的两次连续就诊时DAS28-ESR<2.6）的患者停用TCZ，并在1年内每4周进行一次评估。如果维持持续缓解，则停用加用的csDMARDs，然后停用MTX/PBO。
在556名随机分组的患者中，76%完成了第2年的治疗。进入第2年的患者中，50.4%在实现持续缓解后停用了TCZ，5.9%实现了无药缓解。大多数停用TCZ的患者（84.0%）随后复发，但重新使用TCZ后反应良好。尽管许多患者暂时停用了TCZ，但影像学进展最小，加用治疗更具优势。每100患者年的严重不良事件和严重感染发生率在加用组分别为12.2和4.4，在转换组分别为15.0和3.7。在基线值正常的患者中，加用组丙氨酸转氨酶升高>正常上限3倍的情况（14.3%）比转换组患者（5.4%）更常见。
使用TCZ可以成功实施达标治疗策略以实现持续缓解，之后停用TCZ。无生物制剂缓解维持约3个月，但大多数患者最终复发。重新使用TCZ导致病情迅速改善。
NCT00810199。
