Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, FOT 802, 510 20th Street South, Birmingham, AL, 35294, USA.
Mylan, 1000 Mylan Blvd, Canonsburg, PA, 15317, USA.
Arthritis Res Ther. 2017 Sep 29;19(1):215. doi: 10.1186/s13075-017-1412-z.
Comorbidities may contribute to disease activity and treatment response in rheumatoid arthritis (RA) patients. We defined a somatization comorbidity phenotype (SCP) and examined its influence on response to certolizumab pegol (CZP) using data from the PREDICT trial.
Patients in PREDICT were randomized to the patient-reported Routine Assessment of Patient Index Data 3 (RAPID3) or physician-based Clinical Disease Activity Index (CDAI) for treatment response assessment. Post-hoc analyses identified patients with the SCP, which included diagnosis of depression, fibromyalgia/myalgias, and/or use of medications indicated for treatment of depression, anxiety, or neuropathic pain. The effect of the SCP on RAPID3 or CDAI response at week 12 and low disease activity (LDA; Disease Activity Score in 28 joints based on erythrocyte sedimentation rate ≤ 3.2) at week 52, in week-12 responders, was analyzed using non-parametric analysis of covariance (ANCOVA).
At baseline, 43% (313/733) of patients met the SCP classification. Patients with the SCP were 9% more likely to withdraw from the trial. American College of Rheumatology 20% (ACR20), ACR50, and ACR70 responses were 5-14% lower among those with the SCP, and 11% more patients reported adverse events (AEs). Patients without SCP in the CDAI arm were twice as likely to achieve LDA at week 52 compared with those with SCP (32% versus 16%). No differentiation by SCP was observed in the RAPID3 arm (pooled result 21.5%).
We operationalized a potentially important somatization comorbidity phenotype in a trial setting that was associated with a substantially lower likelihood of treatment response and a higher frequency of AEs. Including large numbers of patients with this phenotype in RA trials may reduce the measured clinical effectiveness of a new molecule.
ClinicalTrials.gov, NCT01255761 . Registered on 6 December 2010.
合并症可能导致类风湿关节炎 (RA) 患者的疾病活动和治疗反应。我们定义了一种躯体化合并症表型 (SCP)，并使用 PREDICT 试验的数据检查其对 certolizumab pegol (CZP) 反应的影响。
PREDICT 中的患者被随机分配到患者报告的常规评估患者指数数据 3 (RAPID3) 或医生为基础的临床疾病活动指数 (CDAI) 进行治疗反应评估。事后分析确定了具有 SCP 的患者，其包括抑郁症、纤维肌痛/肌痛和/或使用治疗抑郁、焦虑或神经病理性疼痛的药物的诊断。在第 12 周和第 52 周时，在第 12 周应答者中，使用非参数协方差分析 (ANCOVA) 分析 SCP 对 RAPID3 或 CDAI 应答的影响和低疾病活动 (LDA；基于红细胞沉降率的 28 个关节疾病活动评分≤3.2)。
在基线时，43%（313/733）的患者符合 SCP 分类。患有 SCP 的患者退出试验的可能性高 9%。在 SCP 患者中，美国风湿病学会 20%（ACR20）、ACR50 和 ACR70 反应低 5-14%，报告不良事件 (AE) 的患者多 11%。在 CDAI 组中没有 SCP 的患者在第 52 周达到 LDA 的可能性是 SCP 患者的两倍（32%对 16%）。在 RAPID3 组中未观察到 SCP 的差异（汇总结果 21.5%）。
我们在试验环境中操作了一种潜在重要的躯体化合并症表型，与治疗反应的可能性显著降低和 AE 频率增加相关。在 RA 试验中纳入大量具有这种表型的患者可能会降低新分子的测量临床效果。
ClinicalTrials.gov，NCT01255761。于 2010 年 12 月 6 日注册。
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