Burmester Gerd-Rűdiger, Kivitz Alan J, Kupper Hartmut, Arulmani Udayasankar, Florentinus Stefan, Goss Sandra L, Rathmann Suchitrita S, Fleischmann Roy M
Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany.
Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA.
Ann Rheum Dis. 2015 Jun;74(6):1037-44. doi: 10.1136/annrheumdis-2013-204769. Epub 2014 Feb 18.
CONCERTO was a randomised, double-blind, parallel-armed study of methotrexate (MTX) in combination with adalimumab to assess whether an increasing trend of efficacy and decreased safety exists when increasing MTX dose in patients with early rheumatoid arthritis (RA).
Early, biologic and MTX-naive RA patients (N=395) were evenly randomised to open-label adalimumab (40 mg every other week) plus weekly blinded 2.5, 5, 10 or 20 mg MTX for 26 weeks. Clinical, radiographic and functional outcomes were analysed using two-sided linear trend tests or one-way analysis of covariance.
Statistically significant increasing trends were observed in the proportion of patients achieving the primary endpoint, 28-joint count disease activity score with C reactive protein (DAS28(CRP)) <3.2 (42.9%, 44.0%, 56.6% and 60.2% for 2.5, 5, 10 or 20 mg/week MTX, respectively), DAS28(CRP) <2.6 and American College of Rheumatology 50/70/90 responses with increasing doses of MTX in combination with adalimumab. No statistical differences in minimal clinically important differences in physical function were detected. Statistically significant trends for achieving low disease activity and remission were demonstrated with increasing MTX dose by validated clinical indices; differences comparing 10 and 20 mg MTX were minimal. Adalimumab serum concentrations increased with ascending dose up to 10 mg MTX. More patients experienced infectious adverse events with increasing MTX dose.
Increasing doses of MTX in combination with adalimumab demonstrated a statistically significant trend in improved clinical outcomes that mimicked the adalimumab pharmacokinetic profile. In early RA patients initiating adalimumab combination therapy, efficacy of 10 and 20 mg/week MTX appeared equivalent.
CONCERTO是一项关于甲氨蝶呤（MTX）联合阿达木单抗的随机、双盲、平行组研究，旨在评估早期类风湿关节炎（RA）患者增加MTX剂量时是否存在疗效增加而安全性降低的趋势。
早期、未使用过生物制剂和MTX的RA患者（N = 395）被均匀随机分为接受开放标签的阿达木单抗（每隔一周40mg）加每周盲法给予2.5、5、10或20mg MTX，共26周。使用双侧线性趋势检验或单向协方差分析对临床、影像学和功能结局进行分析。
在达到主要终点的患者比例方面观察到统计学上显著的增加趋势，即28个关节计数疾病活动评分加C反应蛋白（DAS28(CRP)）<3.2（每周2.5、5、10或20mg MTX的患者分别为42.9%、44.0%、56.6%和60.2%），DAS28(CRP)<2.6以及美国风湿病学会50/70/90反应，随着MTX与阿达木单抗联合剂量增加。在身体功能的最小临床重要差异方面未检测到统计学差异。通过经过验证的临床指标显示，随着MTX剂量增加，实现低疾病活动度和缓解的统计学显著趋势；比较10mg和20mg MTX的差异最小。阿达木单抗血清浓度随着MTX剂量增加至10mg而升高。随着MTX剂量增加，更多患者经历感染性不良事件。
MTX与阿达木单抗联合增加剂量显示出在改善临床结局方面有统计学显著趋势，这与阿达木单抗的药代动力学特征相似。在开始阿达木单抗联合治疗的早期RA患者中，每周10mg和20mg MTX的疗效似乎相当。
