Division of Immunology/Rheumatology, Stanford University School of Medicine, 306 Ramona Road, Palo Alto, CA, 94028, USA.
Arthritis Res Ther. 2009;11(6):R170. doi: 10.1186/ar2859. Epub 2009 Nov 12.
The objective of this study was to assess the impact of certolizumab pegol (CZP) treatment on health-related quality of life (HRQoL), fatigue and other patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA).
Patients with active RA (N = 982) were randomized 2:2:1 to subcutaneous CZP (400 mg at weeks 0, 2 and 4; followed by CZP 200 mg or 400 mg) plus methotrexate (MTX) every other week, or placebo (PBO) plus MTX. PRO assessments included HRQoL, fatigue, physical function, arthritis pain and disease activity. Adjusted mean changes from baseline in all PROs were obtained using analysis of covariance (ANCOVA) applying last observation carried forward (LOCF) imputation. The proportion of patients achieving clinically meaningful improvements in each PRO was obtained using logistic regression and by applying non-responder imputation to missing values after rescue medication or withdrawal. The correlations between PRO responses and clinical responses were also assessed by tetrachoric correlation using non-responder imputation.
Patients treated with CZP plus MTX reported significant (P < 0.001), clinically meaningful improvements in HRQoL at the first assessment (week 12); reductions in fatigue, disease activity and pain and improvements in physical function were reported at week 1. In particular, CZP-treated patients reported improvements in mental health. Mean changes from baseline in the SF-36 Mental Component Summary (MCS) at week 52 for CZP 200 mg and 400 mg plus MTX, and PBO plus MTX were 6.4, 6.4 and 2.1, respectively (P < 0.001). In addition, mental health and vitality scores in CZP-treated patients approached age- and gender-adjusted US population norms. Improvements in all PROs were sustained. Similar benefits were reported with both CZP doses. Changes in SF-36 MCS scores had the lowest correlation with disease activity scores (DAS28) and American College of Rheumatology 20% improvement (ACR20) response rates, while improvements in pain showed the highest correlation.
Treatment with CZP plus MTX resulted in rapid and sustained improvements in all PROs, indicating that the benefits of CZP extend beyond clinical efficacy endpoints into areas that are more relevant and meaningful for patients on a daily basis.
ClinicalTrials.gov NCT00152386.
本研究旨在评估培塞利珠单抗（CZP）治疗对类风湿关节炎（RA）患者健康相关生活质量（HRQoL）、疲劳和其他患者报告结局（PRO）的影响。
982 例活动性 RA 患者随机 2:2:1 接受皮下注射 CZP（第 0、2 和 4 周 400mg，随后 CZP 200mg 或 400mg 每两周 1 次）联合甲氨蝶呤（MTX），或安慰剂（PBO）联合 MTX。PRO 评估包括 HRQoL、疲劳、身体功能、关节炎疼痛和疾病活动度。采用协方差分析（ANCOVA），应用末次观测值结转（LOCF）填补缺失值，对所有 PRO 的基线调整后的平均变化进行分析。采用逻辑回归和在接受救援药物或退出后缺失值采用非应答者填补，获得每个 PRO 中达到临床显著改善的患者比例。采用非应答者填补，通过四分相关系数评估 PRO 反应与临床反应之间的相关性。
接受 CZP 联合 MTX 治疗的患者报告 HRQoL 在第 12 周（第 1 次评估）时出现有统计学意义（P<0.001）、具有临床意义的改善；疲劳、疾病活动度和疼痛减轻，身体功能改善则在第 1 周出现。特别是，接受 CZP 治疗的患者报告心理健康得到改善。在第 52 周，接受 CZP 200mg 和 400mg 联合 MTX 治疗和 PBO 联合 MTX 治疗的 SF-36 心理成分综合评分（MCS）的平均变化分别为 6.4、6.4 和 2.1（P<0.001）。此外，接受 CZP 治疗的患者心理健康和活力评分接近美国年龄和性别调整后的人群正常值。所有 PRO 的改善均持续存在。两种 CZP 剂量均报告了相似的获益。SF-36 MCS 评分的变化与疾病活动评分（DAS28）和美国风湿病学会 20%改善（ACR20）反应率的相关性最低，而疼痛的改善与这些指标的相关性最高。
CZP 联合 MTX 治疗可迅速且持续改善所有 PRO，表明 CZP 的益处不仅限于临床疗效终点，还涵盖了患者日常更相关、更有意义的领域。
ClinicalTrials.gov NCT00152386。
