Fleischmann Roy, van Vollenhoven Ronald F, Vencovský Jiri, Alten Rieke, Davies Owen, Mountian Irina, de Longueville Marc, Carter David, Choy Ernest
Metroplex Clinical Research Center, University of Texas SW Medical Center, Dallas, USA.
Karolinska Institute, Stockholm, Sweden.
Rheumatol Ther. 2017 Jun;4(1):57-69. doi: 10.1007/s40744-017-0060-8. Epub 2017 Mar 28.
The safety and efficacy of certolizumab pegol (CZP) 400 mg every 4 weeks (Q4W) monotherapy (FAST4WARD/NCT00548834) and in combination with methotrexate (MTX) (014/NCT00544154) in active rheumatoid arthritis (RA) has been published previously. This report outlines final long-term outcomes from the open-label extension (OLE) study (015/NCT00160693), which enrolled patients from these randomized controlled trials (RCTs).
Patients who withdrew from or completed the 24-week 014/FAST4WARD RCTs were enrolled and received CZP 400 mg Q4W with/without MTX. Exposure-adjusted event rates (ER) per 100 patient-years (PYs) of adverse events (AEs) and serious AEs (SAEs) were reported for all patients receiving ≥1 dose of CZP in RCTs or OLE (N = 427) between first CZP dose and up to 24 weeks after last CZP dose or study withdrawal. Efficacy assessments included clinical (ACR20/50/70 response rates, TJC, SJC) and patient-reported outcomes (HAQ-DI, PtGADA, pain, fatigue) to week 304 (5.8 years) in the CZP intent-to-treat population. SDAI and CDAI outcomes were analyzed post hoc. Outcomes for CZP monotherapy and CZP+MTX combination-therapy were compared.
Globally, ERs of AEs and SAEs were 408.1 and 25.2 per 100 PY, respectively. Eleven patients had AEs leading to death (ER 0.6). Improvements in clinical and patient-reported outcomes during the 24-week RCTs were maintained to week 304, and were similar between all subpopulations.
The longest exposure duration to date with CZP 400 mg Q4W treatment confirmed the safety profile observed in previous studies. Initial improvements in signs and symptoms of RA, including PROs, were maintained in both CZP monotherapy and CZP + MTX combination-therapy patients.
ClinicalTrials.gov identifier, NCT00160693.
UCB Pharma.
赛妥珠单抗聚乙二醇化（CZP）每4周400mg单药治疗（FAST4WARD/NCT00548834）以及与甲氨蝶呤（MTX）联合使用（014/NCT00544154）在活动性类风湿关节炎（RA）中的安全性和有效性此前已有报道。本报告概述了开放标签扩展（OLE）研究（015/NCT00160693）的最终长期结果，该研究纳入了来自这些随机对照试验（RCT）的患者。
退出或完成24周014/FAST4WARD RCT的患者被纳入研究，并接受每4周400mg CZP，可联合或不联合MTX。报告了在RCT或OLE中接受≥1剂CZP的所有患者（N = 427）在首次CZP给药至最后一剂CZP给药后24周或研究退出期间，每100患者年（PY）的不良事件（AE）和严重不良事件（SAE）的暴露调整事件率（ER）。疗效评估包括在CZP意向性治疗人群中至第304周（5.8年）的临床（美国风湿病学会20/50/70反应率、关节压痛计数、关节肿胀计数）和患者报告结局（健康评估问卷残疾指数、患者全球评估疾病活动度、疼痛、疲劳）。对简化疾病活动指数（SDAI）和临床疾病活动指数（CDAI）结局进行事后分析。比较了CZP单药治疗和CZP + MTX联合治疗的结局。
总体而言，AE和SAE的ER分别为每100 PY 408.1和25.2。11名患者发生导致死亡的AE（ER 0.6）。24周RCT期间临床和患者报告结局的改善维持至第304周，且在所有亚组中相似。
迄今为止，每4周400mg CZP治疗的最长暴露持续时间证实了先前研究中观察到的安全性。在CZP单药治疗和CZP + MTX联合治疗的患者中，RA体征和症状（包括患者报告结局）的初始改善均得以维持。
ClinicalTrials.gov标识符，NCT00160693。
优时比制药公司。
