Molander Viktor, Bower Hannah, Frisell Thomas, Askling Johan
Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Rheumatology, Theme Inflammation and Ageing, Karolinska University Hospital, Stockholm, Sweden.
Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Ann Rheum Dis. 2025 May;84(5):716-725. doi: 10.1016/j.ard.2025.01.020. Epub 2025 Feb 17.
To investigate rates of key safety outcomes in patients with rheumatoid arthritis (RA) initiating biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and in reference cohorts, presented over time since the market entry of each b/tsDMARD class and over calendar period at treatment start.
This was a nationwide register-based cohort study conducted from 2006 to 2022. From the Swedish Rheumatology Quality Register and national registers, we identified treatment initiators of b/tsDMARDs (n = 33,550 initiations), an early bionaive RA cohort (n = 16,011), and a matched general population cohort (n = 111,074). The main outcome was first of either major adverse cardiovascular event, venous thromboembolism, cancer, or serious infection. We stratified rates by time since market entry of each b/tsDMARD class at treatment start, and by calendar year of treatment start. We calculated incidence rates (IRs) and hazard ratios (HRs) using Cox regression and adjusted for patient characteristics.
Overall, 5862 events were observed in the b/tsDMARD initiator cohort. b/tsDMARD treatments initiated >5 (vs <2) years since market entry of that class were associated with lower outcome rates (unadjusted HR = 0.74; 95% CI = 0.67-0.81). This association was attenuated once adjusting for patient characteristics (adjusted HR = 0.93; 95% CI = 0.84-1.03). By contrast, during our study period, adjusted rates declined (adjusted HR = 0.74 and 95% CI = 0.69-0.80 for b/tsDMARDs initiated 2016-2021 vs 2006-2010), despite a constant rate in the background population.
Modest channelling makes the safety profile of b/tsDMARDs appear worse when new on the market. Declining incidences of typical RA comorbidities in b/tsDMARD initiators during recent years suggest that the bar defining an "acceptable" safety profile for new b/tsDMARDs for use in RA should be lower(ed).
研究类风湿关节炎（RA）患者开始使用生物制剂/靶向合成改善病情抗风湿药物（b/tsDMARDs）后的关键安全结局发生率，并与对照队列进行比较，呈现自每类b/tsDMARDs上市以来的时间趋势以及治疗开始时的日历时间段趋势。
这是一项基于全国登记册的队列研究，时间跨度为2006年至2022年。我们从瑞典风湿病质量登记册和国家登记册中，识别出b/tsDMARDs的治疗起始者（n = 33,550次起始治疗）、一个早期未使用过生物制剂的RA队列（n = 16,011）以及一个匹配的普通人群队列（n = 111,074）。主要结局是首次发生重大心血管不良事件、静脉血栓栓塞、癌症或严重感染。我们根据治疗开始时每类b/tsDMARDs上市后的时间以及治疗开始的日历年对发生率进行分层。我们使用Cox回归计算发病率（IRs）和风险比（HRs），并对患者特征进行调整。
总体而言，在b/tsDMARDs起始治疗队列中观察到5862起事件。自某类b/tsDMARDs上市后>5年（vs <2年）开始的b/tsDMARDs治疗与较低的结局发生率相关（未调整的HR = 0.74；95% CI = 0.67 - 0.81）。在对患者特征进行调整后，这种关联减弱（调整后的HR = 0.93；95% CI = 0.84 - 1.03）。相比之下，在我们的研究期间，调整后的发生率有所下降（2016 - 2021年开始使用b/tsDMARDs的调整后HR = 0.74，95% CI = 0.69 - 0.80，而2006 - 2010年开始使用的为对照），尽管背景人群中的发生率保持不变。
适度的选择偏倚使得b/tsDMARDs在刚上市时的安全性看起来更差。近年来b/tsDMARDs起始治疗者中典型RA合并症的发生率下降，这表明用于RA的新b/tsDMARDs定义“可接受”安全性的标准应该降低。
