Emery Paul, Fleischmann Roy M, Hsia Elizabeth C, Xu Stephen, Zhou Yiying, Baker Daniel
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK,
Clin Rheumatol. 2014 Sep;33(9):1239-46. doi: 10.1007/s10067-014-2731-y. Epub 2014 Jul 9.
The purpose of this study was to assess the treatment benefit of golimumab + methotrexate (MTX) vs. MTX monotherapy in MTX-naïve patients with severe active rheumatoid arthritis (RA). This was a post hoc analysis of MTX-naïve RA patients in the GO-BEFORE trial who were randomized to receive placebo + MTX (n = 160), golimumab 50 mg + MTX (n = 159), or golimumab 100 mg + MTX (n = 159). Subsets of patients with severe disease were identified using these baseline criteria: C-reactive protein (CRP) ≥1.5 mg/dL, CRP ≥3.0 mg/dL, swollen joint count (SJC) ≥10 and tender joint count (TJC) ≥12, SJC ≥ 20/TJC ≥ 12, 28-joint count Disease Activity Score using CRP (DAS28-CRP) >5.1, and anti-cyclic citrullinated peptide antibody-positive status. The treatment effect of golimumab + MTX vs. MTX alone was evaluated for these outcomes: the proportions of patients achieving ≥20, 50, and 70 % improvement in the American College of Rheumatology criteria; DAS28-CRP European League Against Rheumatism response; DAS28-CRP <2.6, clinically meaningful improvement in physical function; and change in van der Heijde-Sharp score ≤0 at week 52. Clinical response was greater in the golimumab + MTX groups vs. placebo + MTX for all of the outcomes evaluated. Furthermore, the treatment effect of golimumab + MTX was consistently greater among patients in the severe disease subsets when compared with the overall GO-BEFORE trial population. The treatment benefit of golimumab + MTX vs. MTX monotherapy was most pronounced within the subsets of patients with CRP ≥3.0 mg/dL and SJC ≥ 20/TJC ≥ 12. Following treatment with golimumab + MTX, improvements in RA signs/symptoms and in progression of structural damage were evident for the overall GO-BEFORE population, with the treatment effect more pronounced among patients with severe active disease.
本研究的目的是评估戈利木单抗+甲氨蝶呤（MTX）与MTX单药治疗对初治的重症活动性类风湿关节炎（RA）患者的治疗效果。这是对GO-BEFORE试验中初治RA患者的一项事后分析，这些患者被随机分为接受安慰剂+MTX（n = 160）、戈利木单抗50 mg+MTX（n = 159）或戈利木单抗100 mg+MTX（n = 159）。使用以下基线标准确定重症疾病患者亚组：C反应蛋白（CRP）≥1.5 mg/dL、CRP≥3.0 mg/dL、肿胀关节计数（SJC）≥10且压痛关节计数（TJC）≥12、SJC≥20/TJC≥12、采用CRP的28关节计数疾病活动评分（DAS28-CRP）>5.1以及抗环瓜氨酸肽抗体阳性状态。针对以下结局评估戈利木单抗+MTX与单用MTX的治疗效果：达到美国风湿病学会标准改善≥20%、50%和70%的患者比例；DAS28-CRP欧洲抗风湿病联盟反应；DAS28-CRP<2.6、身体功能有临床意义的改善；以及在第52周时范德海伊德-夏普评分变化≤0。在所有评估的结局方面，戈利木单抗+MTX组的临床反应均优于安慰剂+MTX组。此外，与整个GO-BEFORE试验人群相比，戈利木单抗+MTX在重症疾病亚组患者中的治疗效果始终更佳。在CRP≥3.0 mg/dL和SJC≥20/TJC≥12的患者亚组中，戈利木单抗+MTX对比MTX单药治疗的治疗益处最为显著。在整个GO-BEFORE人群中，接受戈利木单抗+MTX治疗后，RA体征/症状及结构损伤进展均有改善，在重症活动性疾病患者中治疗效果更为显著。
