对于尽管接受甲氨蝶呤治疗但仍患有活动性类风湿关节炎的患者，静脉注射戈利木单抗治疗的影像学益处及临床益处的维持：3期随机、多中心、双盲、安慰剂对照GO-FURTHER试验的1年结果
Radiographic benefit and maintenance of clinical benefit with intravenous golimumab therapy in patients with active rheumatoid arthritis despite methotrexate therapy: results up to 1 year of the phase 3, randomised, multicentre, double blind, placebo controlled GO-FURTHER trial.
作者信息
Weinblatt Michael E, Westhovens Rene, Mendelsohn Alan M, Kim Lilianne, Lo Kim Hung, Sheng Shihong, Noonan Lenore, Lu Jiandong, Xu Zhenhua, Leu Jocelyn, Baker Daniel, Bingham Clifton O
机构信息
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Department of Development and Regeneration KU Leuven, Skeletal Biology and Engineering Research Centre, Leuven, Belgium Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
出版信息
Ann Rheum Dis. 2014 Dec;73(12):2152-9. doi: 10.1136/annrheumdis-2013-203742. Epub 2013 Sep 3.
OBJECTIVE
Report on radiographic effects and maintenance of clinical benefit with intravenous golimumab 2 mg/kg+methotrexate (MTX) for up to week (wk) 52 in active rheumatoid arthritis (RA).
METHODS
Patients (n=592) with active RA (≥6/66 swollen, ≥6/68 tender joints, C reactive protein (CRP) ≥1.0 mg/dL and positive for rheumatoid factor and/or anticyclic citrullinated protein antibody at screening) despite MTX ≥3 months (stable dose of 15-25 mg/week for ≥4 weeks) participated in this multicentre, international, randomised, double blind, placebo controlled, phase 3 study. Patients were randomised (2:1) to receive intravenous golimumab 2 mg/kg or placebo infusions at weeks 0 and 4 and then every 8 weeks; patients continued their stable MTX regimen. Placebo patients started golimumab 2 mg/kg at wk16 (early escape; <10% improvement in tender and swollen joints) or wk24 (crossover by design). Week 24 and wk52 radiographic (van der Heijde-Sharp (vdH-S) scores), clinical efficacy and safety data up to 1 year are reported here.
RESULTS
Significant and rapid clinical improvement was observed up to wk24 of intravenous golimumab therapy. Golimumab+MTX treated patients demonstrated less radiographic progression than placebo treated patients at wk24 (vdH-S score mean change 0.03 vs 1.09; p<0.001) and wk52 (0.13 vs 1.22; p=0.001). Among patients with ≥20% improvement in the American College of Rheumatology response criteria or who achieved a 'good' or 'moderate' response according to the 28 joint Disease Activity Score employing CRP at wk24, approximately 80% maintained this response up until wk52. Through an average of 43.5 weeks of follow-up, 64.6% of patients receiving golimumab+MTX reported adverse events, most commonly non-serious infections.
CONCLUSIONS
In patients with active RA despite MTX, intravenous golimumab+MTX yielded significant inhibition of structural damage at wk24 and wk52, and sustained clinical improvement in signs and symptoms with no new safety signals up to 1 year.
CLINICALTRIALSGOV
NCT00973479, EudraCT 2008-006 064-11.
目的
报告静脉注射戈利木单抗2mg/kg联合甲氨蝶呤（MTX）治疗活动性类风湿关节炎（RA）长达52周的影像学效果及临床获益的维持情况。
方法
尽管使用MTX≥3个月（稳定剂量15 - 25mg/周，持续≥4周），但仍患有活动性RA（筛查时≥6/66个关节肿胀、≥6/68个关节压痛、C反应蛋白（CRP）≥1.0mg/dL且类风湿因子和/或抗环瓜氨酸化蛋白抗体呈阳性）的患者（n = 592）参与了这项多中心、国际、随机、双盲、安慰剂对照的3期研究。患者按2:1随机分组，在第0周和第4周接受静脉注射戈利木单抗2mg/kg或安慰剂输注，随后每8周一次；患者继续其稳定的MTX治疗方案。安慰剂组患者在第16周（早期退出；压痛和肿胀关节改善<10%）或第24周（按设计交叉）开始使用戈利木单抗2mg/kg。本文报告了第24周和第52周的影像学（范德海伊德 - 夏普（vdH - S）评分）、临床疗效以及长达1年的安全性数据。
结果
在静脉注射戈利木单抗治疗的第24周前观察到显著且快速的临床改善。在第24周（vdH - S评分平均变化0.03对1.09；p<0.001）和第52周（0.13对1.22；p = 0.001），戈利木单抗 + MTX治疗的患者比安慰剂治疗的患者影像学进展更少。在第24周根据美国风湿病学会反应标准改善≥20%或根据采用CRP的28个关节疾病活动评分达到“良好”或“中等”反应的患者中，约80%在第52周前维持了该反应。经过平均43.5周的随访，接受戈利木单抗 + MTX治疗的患者中有64.6%报告了不良事件，最常见的是非严重感染。
结论
在尽管使用MTX但仍患有活动性RA的患者中，静脉注射戈利木单抗 + MTX在第24周和第52周显著抑制了结构损伤，并持续改善了体征和症状，长达1年未出现新的安全信号。
临床试验注册
ClinicalTrials.gov：NCT00973479，EudraCT 2008 - 006 064 - 11。
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