Keystone Edward, Heijde Désireé van der, Mason David, Landewé Robert, Vollenhoven Ronald Van, Combe Bernard, Emery Paul, Strand Vibeke, Mease Philip, Desai Chintu, Pavelka Karel
University of Toronto, Toronto, Ontario, Canada.
Arthritis Rheum. 2008 Nov;58(11):3319-29. doi: 10.1002/art.23964.
To evaluate the efficacy and safety of 2 dosage regimens of lyophilized certolizumab pegol (a novel PEGylated anti-tumor necrosis factor agent) as adjunctive therapy to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) with an inadequate response to MTX therapy alone.
In this 52-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 982 patients were randomized 2:2:1 to receive treatment with subcutaneous certolizumab pegol at an initial dosage of 400 mg given at weeks 0, 2, and 4, with a subsequent dosage of 200 mg or 400 mg given every 2 weeks, plus MTX, or placebo plus MTX. Co-primary end points were the response rate at week 24 according to the American College of Rheumatology 20% criteria for improvement (ACR20) and the mean change from baseline in the modified total Sharp score at week 52.
At week 24, ACR20 response rates using nonresponder imputation for the certolizumab pegol 200-mg and 400-mg groups were 58.8% and 60.8%, respectively, as compared with 13.6% for the placebo group. Differences in ACR20 response rates versus placebo were significant at week 1 and were sustained to week 52 (P < 0.001). At week 52, mean radiographic progression from baseline was reduced in patients treated with certolizumab pegol 200 mg (0.4 Sharp units) or 400 mg (0.2 Sharp units) as compared with that in placebo-treated patients (2.8 Sharp units) (P < 0.001 by rank analysis). Improvements in all ACR core set of disease activity measures, including physical function, were observed by week 1 with both certolizumab pegol dosage regimens. Most adverse events were mild or moderate.
Treatment with certolizumab pegol 200 or 400 mg plus MTX resulted in a rapid and sustained reduction in RA signs and symptoms, inhibited the progression of structural joint damage, and improved physical function as compared with placebo plus MTX treatment in RA patients with an incomplete response to MTX.
评估两种剂量方案的聚乙二醇化赛妥珠单抗（一种新型聚乙二醇化抗肿瘤坏死因子药物）作为甲氨蝶呤（MTX）辅助治疗对甲氨蝶呤单药治疗反应不足的活动性类风湿关节炎（RA）患者的疗效和安全性。
在这项为期52周的III期多中心随机双盲安慰剂对照平行组试验中，982例患者按2:2:1随机分组，分别接受皮下注射聚乙二醇化赛妥珠单抗治疗，初始剂量为400mg，于第0、2和4周给药，随后每2周给药200mg或400mg，加用MTX，或接受安慰剂加MTX治疗。共同主要终点为根据美国风湿病学会20%改善标准（ACR20）在第24周时的缓解率，以及在第52周时改良总Sharp评分相对于基线的平均变化。
在第24周时，采用无反应者推算法，聚乙二醇化赛妥珠单抗200mg组和400mg组的ACR20缓解率分别为58.8%和60.8%，而安慰剂组为13.6%。与安慰剂相比，ACR20缓解率在第1周时的差异具有显著性，并持续至第52周（P<0.001）。在第52周时，与接受安慰剂治疗的患者（2.8个Sharp单位）相比，接受200mg（0.4个Sharp单位）或400mg（0.2个Sharp单位）聚乙二醇化赛妥珠单抗治疗的患者从基线开始的平均影像学进展有所降低（秩分析，P<0.001）。在第1周时，两种聚乙二醇化赛妥珠单抗剂量方案均观察到包括身体功能在内的所有ACR核心疾病活动指标有所改善。大多数不良事件为轻度或中度。
与接受安慰剂加MTX治疗的对MTX反应不完全的RA患者相比，接受200mg或400mg聚乙二醇化赛妥珠单抗加MTX治疗可使RA体征和症状迅速且持续减轻，抑制关节结构损伤的进展，并改善身体功能。
