Bristol-Myers Squibb, Princeton, New Jersey.
Brigham and Women's Hospital, Boston, Massachusetts.
Arthritis Care Res (Hoboken). 2020 Feb;72(2):176-183. doi: 10.1002/acr.24071. Epub 2020 Jan 13.
Seropositivity for anti-citrullinated protein antibody (ACPA)/rheumatoid factor (RF) in rheumatoid arthritis (RA) is associated with increased overall mortality; however, the association between antibody titers and mortality is not well established. Investigating relationships between antibody titers and mortality may clarify their role in RA pathogenesis. This study was undertaken to evaluate the association of antibody titers with mortality and its modification by disease-modifying antirheumatic drugs (DMARDs).
Eligible patients with established RA were identified through administrative claims data linked to laboratory results (2005-2016). Patients were categorized by positivity status for ACPA, RF, or both. Patients were further divided into groups by autoantibody titers. DMARD-exposed patients were categorized into biologic DMARD (bDMARD) and conventional DMARD (cDMARD) subcohorts. Crude mortality rates/1,000 patient-years and Kaplan-Meier curves were compared between antibody categories. Adjusted Cox proportional hazards regression and sensitivity (propensity-matched patients) analyses were conducted.
Overall, 53,849 and 79,926 patients had evaluable ACPA and RF status, respectively. For both autoantibodies, mortality rates were significantly higher in seropositive versus seronegative patients (risk increase of 48.0% and 44.0% in ACPA- and RF-positive patients, respectively; P < 0.001 each). Mortality rates were greatest in patients with higher versus lower autoantibody titers (ACPA hazard ratio [HR] 1.60 [95% confidence interval (95% CI]) 1.45-1.76]; RF HR 1.78 [95% CI 1.66-1.91]). In cDMARD-exposed patients, HRs were higher in seropositive versus seronegative cohorts; in bDMARD-exposed patients, there was no difference in mortality by serostatus.
Elevated ACPA/RF titers were independently associated with increased mortality among patients with RA and persisted in patients treated with cDMARDs but not with bDMARDs.
抗瓜氨酸化蛋白抗体（ACPA）/类风湿因子（RF）在类风湿关节炎（RA）中的阳性与总死亡率增加相关；然而，抗体滴度与死亡率之间的关系尚未得到很好的确定。研究抗体滴度与死亡率之间的关系可能有助于阐明它们在 RA 发病机制中的作用。本研究旨在评估抗体滴度与死亡率的相关性及其与疾病修饰抗风湿药物（DMARDs）的相关性。
通过与实验室结果相关联的行政索赔数据，确定已确诊的 RA 患者（2005-2016 年）。根据 ACPA、RF 或两者的阳性状态对患者进行分类。根据自身抗体滴度，患者进一步分为组。暴露于 DMARD 的患者分为生物 DMARD（bDMARD）和常规 DMARD（cDMARD）亚组。比较抗体类别之间的粗死亡率/1000 患者年和 Kaplan-Meier 曲线。进行调整后的 Cox 比例风险回归和敏感性（倾向匹配患者）分析。
总体而言，分别有 53849 名和 79926 名患者具有可评估的 ACPA 和 RF 状态。对于两种自身抗体，阳性患者的死亡率明显高于阴性患者（ACPA 阳性患者的风险增加 48.0%和 44.0%；RF 阳性患者的风险增加 44.0%和 44.0%；P<0.001 ）。与较低抗体滴度相比，更高抗体滴度患者的死亡率更高（ACPA 风险比[HR]1.60[95%置信区间（95%CI）]1.45-1.76；RF HR 1.78[95%CI 1.66-1.91]）。在 cDMARD 暴露患者中，阳性患者的 HR 高于阴性患者；在 bDMARD 暴露患者中，血清状态与死亡率无差异。
升高的 ACPA/RF 滴度与 RA 患者的死亡率增加独立相关，并在接受 cDMARD 治疗的患者中持续存在，但在接受 bDMARD 治疗的患者中则无差异。
