Curtis Jeffrey R, Chen L, Luijtens K, Navarro-Millan I, Goel N, Gervitz L, Weinblatt M
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, FOT 805D, 510 20th Street South, Birmingham, Alabama 35294, USA.
Arthritis Rheum. 2011 Aug;63(8):2203-8. doi: 10.1002/art.30387.
To determine whether certolizumab pegol (CZP) dosage escalation from 200 mg to 400 mg every other week benefits some patients with rheumatoid arthritis (RA).
In the extension of the Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) study into an open-label study, all patients received CZP 400 mg every other week in combination with methotrexate (MTX). Before the open-label phase of the study, patients had received CZP 200 mg or 400 mg every other week, or placebo every other week, as add-on therapy to MTX. The open-label study included those who had completed the RAPID 1 study (to week 52) and also those who had been withdrawn from the study (at week 16, due to inadequate response). At 12 weeks and 48 weeks after enrollment in the open-label study, changes in the Disease Activity Score in 28 joints (DAS28) were compared in dose-escalation patients (200 mg increased to 400 mg every other week) versus stable-dosage patients (400 mg every other week), using cumulative probability plots of individual patient-level data.
In the group of patients who had completed the RAPID 1 study and had moderate or severe disease activity at entry into the open-label study, and in those who had been withdrawn early from the RAPID 1 study, the median DAS28 improvements 12 weeks after enrollment into the open-label study were similar in the dose-escalation and stable-dose groups. Individual patient-level data revealed no greater likelihood of response in the group of patients who received an increased dosage of CZP versus those in whom a stable dosage was maintained, whether they had completed the RAPID 1 study or had been withdrawn early.
Although patient heterogeneity in clinical settings is acknowledged, the present results indicate that increasing the dose of CZP from 200 mg to 400 mg offers little additional benefit in RA, even for selected patients.
确定每两周将赛妥珠单抗（CZP）剂量从200mg增至400mg是否能使部分类风湿关节炎（RA）患者获益。
在类风湿关节炎预防结构损伤1（RAPID 1）研究扩展为开放标签研究中，所有患者每两周接受400mg CZP联合甲氨蝶呤（MTX）治疗。在研究的开放标签阶段之前，患者每两周接受200mg或400mg CZP，或每两周接受安慰剂，作为MTX的附加治疗。开放标签研究纳入了完成RAPID 1研究（至第52周）的患者以及那些已退出研究的患者（在第16周，因反应不足）。在开放标签研究入组后12周和48周，使用个体患者水平数据的累积概率图，比较剂量递增患者（每两周从200mg增至400mg）与稳定剂量患者（每两周400mg）的28个关节疾病活动评分（DAS28）变化。
在完成RAPID 1研究且在进入开放标签研究时具有中度或重度疾病活动的患者组中，以及在早期退出RAPID 1研究的患者中，开放标签研究入组12周后，剂量递增组和稳定剂量组的DAS28改善中位数相似。个体患者水平数据显示，接受增加剂量CZP的患者组与维持稳定剂量的患者组相比，无论他们是完成了RAPID 1研究还是早期退出，均无更大的反应可能性。
尽管承认临床环境中患者存在异质性，但目前结果表明，将CZP剂量从200mg增至400mg对RA几乎没有额外益处，即使对于特定患者也是如此。
