Vashisht Priyanka, Sayles Harlan, Cannella Amy C, Mikuls Ted R, Michaud Kaleb
Priyanka Vashisht, MD, Harlan Sayles, MS, Amy C. Cannella, MD, MS, Ted R. Mikuls, MD, MSPH: VA Nebraska-Western Iowa Health Care System and Nebraska Arthritis Outcomes Research Center, University of Nebraska Medical Center, Omaha, Nebraska.
Kaleb Michaud, PhD: VA Nebraska-Western Iowa Health Care System and Nebraska Arthritis Outcomes Research Center, University of Nebraska Medical Center, Omaha, Nebraska, and the National Bank for Rheumatic Diseases, Wichita, Kansas.
Arthritis Care Res (Hoboken). 2016 Oct;68(10):1478-88. doi: 10.1002/acr.22860. Epub 2016 Sep 16.
Randomized controlled trials (RCTs) have consistently demonstrated the efficacy of biologic agents in treating patients with rheumatoid arthritis (RA) who satisfy strict eligibility criteria, yet studies report that a majority of RA patients in the US have had biologic treatment exposure. We identified the proportion of RA patients in clinical practice satisfying entry criteria for biologic agent RCTs.
Eligibility criteria of 30 RCTs of 10 Food and Drug Administration-approved biologic agents to treat RA were reviewed, summarized, and applied to 2 observational clinical cohorts: the Veterans Affairs Rheumatoid Arthritis registry (VARA; n = 1,523) and the Rheumatology and Arthritis Investigational Network Database (RAIN-DB; n = 1,548). Patients at a single clinical encounter were assessed for overall trial eligibility as well as eligibility across 3 domains: demographics, disease activity, and medication exposure.
The mean percentage of patients that satisfied eligibility criteria was 3.7% (interquartile range [IQR] 1.5-3.1) in VARA and 7.1% (IQR 4.4-7.7) in RAIN-DB. Ineligibility was most often due to low disease activity, specifically low joint counts. The mean Disease Activity Score in 28 joints at enrollment was 6.59 (range 6.1-7.1) across RCTs versus 3.87 (0.07-8.69) in VARA and 3.65 (0.49-7.21) in RAIN-DB. RCTs for non-tumor necrosis factor (TNF) inhibitor biologic agents were more restrictive than RCTs for TNF inhibitors. There was no trend in eligibility by RCT study publication or drug approval date.
The vast majority of RA patients from our clinical cohorts did not satisfy criteria for participation in biologic agent RCTs. These findings underscore the need for caution in extrapolating trial results to day-to-day management of RA patients and may provide insight into the differential responses to biologic agents reported in prior observational studies.
随机对照试验（RCT）一直证明生物制剂在治疗符合严格入选标准的类风湿关节炎（RA）患者方面的疗效，但研究报告称美国大多数RA患者曾接受过生物治疗。我们确定了临床实践中符合生物制剂RCT入选标准的RA患者比例。
回顾、总结了美国食品药品监督管理局批准的10种治疗RA的生物制剂的30项RCT的入选标准，并将其应用于2个观察性临床队列：退伍军人事务部类风湿关节炎登记处（VARA；n = 1523）和风湿病与关节炎研究网络数据库（RAIN-DB；n = 1548）。对单次临床就诊的患者进行整体试验入选资格评估以及3个领域的入选资格评估：人口统计学、疾病活动度和药物暴露情况。
VARA队列中符合入选标准的患者平均百分比为3.7%（四分位间距[IQR] 1.5 - 3.1），RAIN-DB队列中为7.1%（IQR 4.4 - 7.7）。不符合入选标准最常见的原因是疾病活动度低，尤其是关节计数低。RCT中入组时28个关节的平均疾病活动评分是6.59（范围6.1 - 7.1），而VARA队列中为3.87（0.07 - 8.69），RAIN-DB队列中为3.65（0.49 - 7.21）。非肿瘤坏死因子（TNF）抑制剂生物制剂的RCT比TNF抑制剂的RCT限制更严格。入选资格与RCT研究发表时间或药物批准日期之间没有趋势关系。
我们临床队列中的绝大多数RA患者不符合参与生物制剂RCT的标准。这些发现强调在将试验结果外推至RA患者日常管理时需谨慎，并可能为先前观察性研究中报道的生物制剂差异反应提供见解。
