Comparative Safety of Biologic and Targeted-Synthetic DMARDs in Patients With Rheumatoid Arthritis: A Multi-Database Real-World Cohort Study.

IF 2.4 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacoepidemiology and Drug Safety Pub Date : 2025-08-01 DOI:10.1002/pds.70193

Yinzhu Jin, Jun Liu, Rishi J Desai

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Abstract

Objectives: To examine the comparative risk of malignancy, venous thromboembolism (VTE), and heart failure (HF) associated with biologic/targeted synthetic disease-modifying antirheumatic drugs (b/ts DMARDs) in patients with rheumatoid arthritis (RA).

Methods: We conducted an observational cohort study using 3 US insurance claims databases: Medicare (2009-2019), MarketScan (2009-2020), and Optum's de-identified Clinformatics Data Mart Database (CDM, 2009-2022). We included adults with RA initiating abatacept (reference), tumor necrosis factor inhibitors (TNFi), rituximab, interleukin-6 inhibitors (IL-6i), or Janus kinase inhibitors (JAKi). We used an as-treated approach as the primary analysis to estimate outcome incidence. Inverse probability of treatment weighting was applied to adjust for confounding. Database-specific hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox-proportional hazard models, then combined through random-effects meta-analysis.

Results: We identified 26 908 abatacept, 11 176 IL-6i, 115 437 TNFi, 14 045 JAKi, and 12 097 rituximab initiators. Weighted HR (95% CI) of malignancy was 0.73 (0.60-0.88) for IL-6i, 0.85 (0.60-1.19) for JAKi, 1.30 (1.14-1.49) for rituximab, and 0.93 (0.85-1.02) for TNFi, compared to abatacept. Weighted HR (95% CI) for VTE was 0.92 (0.62-1.35), 1.17 (0.73-1.86), 1.43 (1.50-1.95), and 1.16 (0.93-1.46), respectively. Weighted HR (95% CI) for HF was 1.00 (0.69-1.46), 1.24 (0.62-2.51), 1.52 (1.04-2.22), and 1.54 (1.22-1.94), respectively.

Conclusion: We observed increased risks of malignancy, VTE, and HF among rituximab initiators; an increased risk of HF among TNFi initiators; and a lower risk of malignancy among IL-6i initiators, all compared to abatacept initiators. These findings should be interpreted with caution due to the potential influence of residual confounding.

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生物制剂和靶向合成DMARDs在类风湿关节炎患者中的比较安全性：一项多数据库真实世界队列研究

目的：研究类风湿性关节炎（RA）患者与生物/靶向合成疾病改善抗风湿药物（b/ts DMARDs）相关的恶性肿瘤、静脉血栓栓塞（VTE）和心力衰竭（HF）的比较风险。方法：我们使用3个美国保险索赔数据库进行了一项观察性队列研究：Medicare（2009-2019）、MarketScan（2009-2020）和Optum的去识别临床数据集市数据库（CDM, 2009-2022）。我们纳入了接受阿巴他普（参考）、肿瘤坏死因子抑制剂（TNFi）、利妥昔单抗、白细胞介素-6抑制剂（IL-6i）或Janus激酶抑制剂（JAKi）治疗的RA成人患者。我们使用治疗方法作为主要分析来估计结局发生率。应用处理加权逆概率来调整混杂。使用cox比例风险模型估计数据库特定风险比（HR）和95%置信区间（CI），然后通过随机效应荟萃分析进行组合。结果：我们鉴定了26 908个abatept， 11 176个IL-6i， 115 437个TNFi， 14 045个JAKi和12 097个利妥昔单抗启动剂。与阿巴接受相比，IL-6i的加权HR （95% CI）为0.73 (0.60-0.88)，JAKi为0.85(0.60-1.19)，利妥昔单抗为1.30 (1.14-1.49)，TNFi为0.93（0.85-1.02）。VTE的加权HR （95% CI）分别为0.92（0.62-1.35）、1.17（0.73-1.86）、1.43（1.50-1.95）和1.16（0.93-1.46）。HF的加权HR （95% CI）分别为1.00（0.69-1.46）、1.24（0.62-2.51）、1.52（1.04-2.22）和1.54（1.22-1.94）。结论：我们观察到利妥昔单抗起始剂中恶性肿瘤、静脉血栓栓塞和心衰的风险增加；TNFi发起者发生HF的风险增加；与abataccept启动者相比，IL-6i启动者患恶性肿瘤的风险更低。由于残留混杂的潜在影响，这些发现应谨慎解释。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacoepidemiology and Drug Safety 医学-药学

CiteScore

4.80

自引率

7.70%

发文量

173

审稿时长

3 months

期刊介绍： The aim of Pharmacoepidemiology and Drug Safety is to provide an international forum for the communication and evaluation of data, methods and opinion in the discipline of pharmacoepidemiology. The Journal publishes peer-reviewed reports of original research, invited reviews and a variety of guest editorials and commentaries embracing scientific, medical, statistical, legal and economic aspects of pharmacoepidemiology and post-marketing surveillance of drug safety. Appropriate material in these categories may also be considered for publication as a Brief Report. Particular areas of interest include: design, analysis, results, and interpretation of studies looking at the benefit or safety of specific pharmaceuticals, biologics, or medical devices, including studies in pharmacovigilance, postmarketing surveillance, pharmacoeconomics, patient safety, molecular pharmacoepidemiology, or any other study within the broad field of pharmacoepidemiology; comparative effectiveness research relating to pharmaceuticals, biologics, and medical devices. Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, as these methods are truly used in the real world; methodologic contributions of relevance to pharmacoepidemiology, whether original contributions, reviews of existing methods, or tutorials for how to apply the methods of pharmacoepidemiology; assessments of harm versus benefit in drug therapy; patterns of drug utilization; relationships between pharmacoepidemiology and the formulation and interpretation of regulatory guidelines; evaluations of risk management plans and programmes relating to pharmaceuticals, biologics and medical devices.