A Phase III Study Evaluating Continuation, Tapering, and Withdrawal of Certolizumab Pegol After One Year of Therapy in Patients With Early Rheumatoid Arthritis.
A Phase III Study Evaluating Continuation, Tapering, and Withdrawal of Certolizumab Pegol After One Year of Therapy in Patients With Early Rheumatoid Arthritis.
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DOI：
10.1002/art.40196
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Emery P
中科院分区：
文献类型：
--
作者：
Weinblatt ME;Bingham CO 3rd;Burmester GR;Bykerk VP;Furst DE;Mariette X;van der Heijde D;van Vollenhoven R;VanLunen B;Ecoffet C;Cioffi C;Emery P
在接受缓解疾病抗风湿药物治疗的早期类风湿性关节炎 (RA) 患者中，使用标准剂量的聚乙二醇赛妥珠单抗 (CZP)（每 2 周 200 mg 加优化甲氨蝶呤）治疗 1 年后，疾病活动度持续较低（第 40 周和第 52 周红细胞沉降率均≤3.2，28 个关节的疾病活动评分） [MTX]），我们评估了以标准剂量或降低频率（每 4 周 200 mg 加 MTX）继续 CZP 治疗在维持低疾病活动度额外一年方面是否优于停止 CZP（安慰剂加 MTX）。我们研究第 1 期的总共 293 名患者在第 2 期按 2:3:2 重新随机分配至标准剂量 CZP (n = 84)、降低频率的 CZP (n = 127) 或安慰剂加 MTX（CZP 停止）(n = 82)。主要终点是在第 52-104 周内保持低疾病活动度且没有发作的患者百分比。我们使用了分层测试方案，将标准剂量的 CZP 与停止使用的 CZP 进行比较。如果达到 P < 0.05，则将频率降低的 CZP 与停止的 CZP 进行比较（无应答者插补）。第 1 期的 293 名患者比预计的患者少 36%，符合第 2 期的患者数量较少。与停止 CZP 的患者相比，接受标准治疗和减少频率治疗方案治疗的患者保持较低疾病活动度的比例较高（分别为 48.8% 和 53.2%，对比 39.2% [分别为 P = 0.112 和 P = 0.041；名义 P 值，第一个层次测试不 重要的]）。放射学无进展（改良 Sharp/van der Heijde 评分相对基线变化≤0.5；分别为 79.2% 和 77.9% 的患者，对比 70.3%）和正常身体功能（健康评估问卷残疾指数评分≤0.5；分别为 71.4% 和 70.6% 的患者，对比 57.0%）观察到类似的趋势。所有组之间的安全性相似，持续 CZP 至 104 周没有发现新的安全信号。没有死亡报告。该研究未能达到其主要终点。然而，CZP 加 MTX 的标准剂量和降低频率剂量之间没有临床意义的差异；两者都比停止 CZP 更有效地控制 RA。
In disease‐modifying antirheumatic drug–naive patients with early rheumatoid arthritis (RA) who had achieved sustained low disease activity (a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate of ≤3.2 at both week 40 and week 52) after 1 year of treatment with certolizumab pegol (CZP) at a standard dose (200 mg every 2 weeks plus optimized methotrexate [MTX]), we evaluated whether continuation of CZP treatment at a standard dose or at a reduced frequency (200 mg every 4 weeks plus MTX) was superior to stopping CZP (placebo plus MTX) in maintaining low disease activity for 1 additional year. A total of 293 patients from period 1 of our study were re‐randomized 2:3:2 in period 2 to CZP at a standard dose (n = 84), CZP at a reduced frequency (n = 127), or placebo plus MTX (CZP stopped) (n = 82). The primary end point was the percentage of patients who maintained low disease activity throughout weeks 52–104 without flares. We used a hierarchical testing scheme, comparing CZP at a standard dose with CZP stopped. If P < 0.05 was achieved, then CZP at a reduced frequency was compared with CZP stopped (nonresponder imputation). The 293 patients from period 1 represented 36% fewer patients than projected, yielding a smaller number of patients eligible for period 2. Higher proportions of patients treated with the standard and reduced frequency regimens maintained low disease activity than those who had stopped CZP (48.8% and 53.2%, respectively, versus 39.2% [P = 0.112 and P = 0.041, respectively; nominal P value, first hierarchical test not significant]). Similar trends were observed for radiographic nonprogression (change from baseline of ≤0.5 in modified Sharp/van der Heijde score; 79.2% and 77.9% of patients, respectively, versus 70.3%) and normative physical function (Health Assessment Questionnaire disability index score of ≤0.5; 71.4% and 70.6% of patients, respectively, versus 57.0%). Safety profiles were similar between all groups, with no new safety signals identified for continuing CZP to week 104. No deaths were reported. The study failed to meet its primary end point. However, there were no clinically meaningful differences between the standard and reduced frequency doses of CZP plus MTX; both controlled RA more effectively than stopping CZP.
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影响因子：
27.4
作者：
Atsumi T;Yamamoto K;Takeuchi T;Yamanaka H;Ishiguro N;Tanaka Y;Eguchi K;Watanabe A;Origasa H;Yasuda S;Yamanishi Y;Kita Y;Matsubara T;Iwamoto M;Shoji T;Okada T;van der Heijde D;Miyasaka N;Koike T
通讯作者：
Koike T
影响因子：
27.4
作者：
Emery, P.;Bingham, C. O., III;Weinblatt, M. E.
通讯作者：
Weinblatt, M. E.
影响因子：
4.9
作者：
Nagy G;van Vollenhoven RF
通讯作者：
van Vollenhoven RF
影响因子：
6.2
作者：
Emamikia, Sharzad;Arkema, Elizabeth V.;van Vollenhoven, Ronald
通讯作者：
van Vollenhoven, Ronald
影响因子：
27.4
作者：
Detert, Jacqueline;Bastian, Hans;Burmester, Gerd-R
通讯作者：
Burmester, Gerd-R