Pawar Ajinkya, Desai Rishi J, He Mengdong, Bessette Lily, Kim Seoyoung C
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
ACR Open Rheumatol. 2021 Aug;3(8):531-539. doi: 10.1002/acr2.11292. Epub 2021 Jul 1.
The objective of this study was to compare the incidence rate of nonvertebral osteoporotic fractures (NVFs) in patients with rheumatoid arthritis (RA) initiating one of the nine biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).
We analyzed claims data from Optum (2008 to March 2019), Medicare, and MarketScan (2008-2017) to identify adults with RA who newly initiated b/tsDMARDs. Adalimumab was the most frequently used and was thus selected as a reference. The primary outcome was a composite of incident NVFs, including hip, humerus, pelvis, and wrist fractures, based on validated algorithms. We adjusted for greater than 70 potential confounders in each database through propensity score-based inverse probability treatment weighting. Follow-up time started the day after cohort entry until the first occurrence of one of the following: outcome, treatment discontinuation, switching, nursing home admission, death, disenrollment, or end of study period. For each drug comparison, weighted Cox proportional hazards models estimated the hazard ratios (HRs) and 95% confidence intervals (CIs). Secondary analyses were conducted in patients switching from a tumor necrosis factor inhibitor to a different b/tsDMARD.
A total of 134,693 b/tsDMARD initiators were identified across three databases. The adjusted HRs showed similar risk of composite NVFs in all b/tsDMARD exposures compared with adalimumab: abatacept, HR 1.03 (95% CI 0.82-1.30); certolizumab, HR 1.08 (95% CI 0.79-1.49); etanercept, HR 1.12 (95% CI 0.89-1.40); golimumab, HR 0.91 (95% CI 0.59-1.39); infliximab, HR 1.03 (95% CI 0.84-1.28); rituximab, HR 1.07 (95% CI 0.74-1.55); tocilizumab, HR 1.24 (95% CI 0.71-2.17); and tofacitinib, HR 1.07 (95% CI 0.69-1.64). Secondary analyses showed similar results.
This multidatabase cohort study found no differences in the risk of NVFs across individual b/tsDMARDs for RA, which provides reassurance to physicians prescribing b/tsDMARDs, especially to patients at high risk of developing NVFs.
本研究的目的是比较开始使用九种生物或靶向合成抗风湿药物（b/tsDMARDs）之一的类风湿关节炎（RA）患者非椎骨骨质疏松性骨折（NVFs）的发病率。
我们分析了Optum（2008年至2019年3月）、医疗保险和MarketScan（2008 - 2017年）的理赔数据，以确定新开始使用b/tsDMARDs的RA成人患者。阿达木单抗是使用最频繁的药物，因此被选作对照。主要结局是基于经过验证的算法得出的包括髋部、肱骨、骨盆和腕部骨折在内的新发NVFs的复合结局。我们通过基于倾向评分的逆概率治疗加权法对每个数据库中的70多个潜在混杂因素进行了调整。随访时间从队列入组后的第二天开始，直至出现以下情况之一：结局、治疗中断、换药、入住养老院、死亡、退出研究或研究期结束。对于每种药物比较，加权Cox比例风险模型估计风险比（HRs）和95%置信区间（CIs）。在从肿瘤坏死因子抑制剂换用另一种b/tsDMARD的患者中进行了二次分析。
在三个数据库中共识别出134,693名开始使用b/tsDMARDs的患者。调整后的HRs显示，与阿达木单抗相比，所有b/tsDMARD暴露的复合NVFs风险相似：阿巴西普，HR 1.03（95%CI 0.82 - 1.30）；赛妥珠单抗，HR 1.08（95%CI 0.79 - 1.49）；依那西普，HR 1.12（95%CI 0.89 - 1.40）；戈利木单抗，HR 0.91（95%CI 0.59 - 1.39）；英夫利昔单抗，HR 1.03（95%CI 0.84 - 1.28）；利妥昔单抗，HR 1.07（95%CI 0.74 - 1.55）；托珠单抗，HR 1.24（95%CI 0.71 - 2.17）；托法替布，HR 1.07（95%CI 0.69 - 1.64）。二次分析显示了相似的结果。
这项多数据库队列研究发现，RA患者使用不同的b/tsDMARDs发生NVFs的风险没有差异，这为开具b/tsDMARDs处方的医生，尤其是有发生NVFs高风险的患者提供了安心的依据。
