Kaeley Gurjit S, Evangelisto Amy M, Nishio Midori J, Goss Sandra L, Liu Shufang, Kalabic Jasmina, Kupper Hartmut
From the University of Florida College of Medicine, Jacksonville, Florida; Arthritis, Rheumatic and Back Disease Associates, Voorhees, New Jersey; Diablo Clinical Research, Walnut Creek, California; AbbVie Inc., North Chicago, Illinois, USA; AbbVie Deutschland GmbH and Co. KG., Ludwigshafen, Germany.G.S. Kaeley, MBBS, MRCP, University of Florida College of Medicine; A.M. Evangelisto, MD, Arthritis, Rheumatic and Back Disease Associates; M.J. Nishio, MD, Diablo Clinical Research; S.L. Goss, PhD, AbbVie Inc.; S. Liu, PhD, AbbVie Inc.; J. Kalabic, MD, AbbVie Inc.; H. Kupper, MD, AbbVie Deutschland GmbH and Co. KG.
J Rheumatol. 2016 Aug;43(8):1480-9. doi: 10.3899/jrheum.151009. Epub 2016 Jun 15.
To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA).
MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions.
Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar.
In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.
在甲氨蝶呤（MTX）治疗反应不足的中度至重度活动性类风湿关节炎（RA）患者中，研究在启动阿达木单抗（ADA）时降低MTX剂量的临床和超声（US）结果。
MUSICA（NCT01185288）是一项双盲、随机、平行组研究，309例RA患者在筛查前接受MTX≥15mg/周治疗≥12周。患者被随机分为高剂量（20mg/周）或低剂量（7.5mg/周）MTX组；所有患者每隔一周接受40mg开放标签的ADA治疗，共24周。主要终点是基于C反应蛋白的第24周28关节疾病活动评分（DAS28-CRP），以15%的界值检验低剂量MTX的非劣效性。使用包含OMERACT病理定义的10关节半定量系统对US图像进行评分，评估滑膜增生、血管形成和骨侵蚀。
两组在加用ADA后临床指标均迅速改善。比较低剂量（4.12，95%CI 3.88-4.34）与高剂量MTX（3.75，95%CI 3.52-3.97）时，平均DAS28-CRP的差异（0.37，95%CI 0.07-0.66）具有统计学意义，未达到非劣效性。大多数临床、功能和US结果未检测到统计学显著差异。药代动力学和安全性概况相似。
在MUSICA研究中，主要终点第24周平均DAS28-CRP未达到低剂量MTX组的非劣效性。尽管两个MTX剂量组之间的差异较小，但我们的研究结果不支持在启动ADA的MTX治疗反应不足的患者中常规降低MTX剂量。
