托法替布与恶性肿瘤风险：来自类风湿关节炎常规治疗患者托法替布安全性研究（STAR-RA）的结果。
Tofacitinib and Risk of Malignancy: Results From the Safety of Tofacitinib in Routine Care Patients With Rheumatoid Arthritis (STAR-RA) Study.
机构信息
Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Division of Pharmacoepidemiology and Pharmacoeconomics, and Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
出版信息
Arthritis Rheumatol. 2022 Oct;74(10):1648-1659. doi: 10.1002/art.42250. Epub 2022 Sep 1.
OBJECTIVES
Results of the ORAL Surveillance safety trial have indicated that there is an increased risk for the development of malignancies with tofacitinib therapy when compared to treatment with tumor necrosis factor inhibitors (TNFi). This study was undertaken to further examine this safety concern in rheumatoid arthritis (RA) patients in a real-world setting.
METHODS
Using US insurance claims data from Optum Clinformatics (2012-2020), IBM MarketScan Research Databases (2012-2018), and Medicare (parts A, B, and D, 2012-2017), we created 2 cohorts of RA patients who had initiated treatment with tofacitinib or TNFi. The first cohort, designated the real-world evidence (RWE) cohort, included RA patients from routine care. For the second cohort, designated the randomized controlled trial (RCT)-duplicate cohort, we emulated the inclusion and exclusion criteria that were applied in the ORAL Surveillance trial of tofacitinib, which allowed us to assess the comparability of our results with the results of that trial. Cox proportional hazards models with propensity score fine-stratification weighting were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of any malignancy (excluding nonmelanoma skin cancer). Database-specific estimates were meta-analyzed using fixed-effects models with inverse-variance weighting.
RESULTS
The RWE cohort consisted of 83,295 patients, including 10,504 patients (12.6%) who received treatment with tofacitinib. The pooled weighted HR for the primary outcome of any malignancy associated with tofacitinib treatment compared to any malignancy associated with TNFi therapy was 1.01 (95% CI 0.83, 1.22) in the RWE cohort and 1.17 (95% CI 0.85, 1.62) in the RCT-duplicate cohort (compared to the ORAL Surveillance trial HR of 1.48 [95% CI 1.04, 2.09]).
CONCLUSION
We did not find evidence of an increased risk of malignancy development with tofacitinib therapy, in comparison with TNFi therapy, in RA patients treated in a real-world setting. However, our results cannot rule out the possibility of an increase in risk that may accrue with a longer duration of treatment with tofacitinib.
目的
ORAL Surveillance 安全性试验的结果表明，与肿瘤坏死因子抑制剂（TNFi）治疗相比，托法替布治疗会增加恶性肿瘤的发病风险。本研究旨在类风湿关节炎（RA）患者的真实世界环境中进一步探讨这一安全性问题。
方法
我们使用 Optum Clinformatics（2012-2020 年）、IBM MarketScan 研究数据库（2012-2018 年）和 Medicare（A、B 和 D 部分，2012-2017 年）的美国保险索赔数据，创建了接受托法替布或 TNFi 治疗的 2 个 RA 患者队列。第一个队列，指定为真实世界证据（RWE）队列，包括常规护理中的 RA 患者。对于第二个队列，指定为随机对照试验（RCT）-重复队列，我们模拟了托法替布的 ORAL Surveillance 试验中应用的纳入和排除标准，这使我们能够评估我们的结果与该试验结果的可比性。使用倾向评分精细分层加权的 Cox 比例风险模型来估计任何恶性肿瘤（不包括非黑色素瘤皮肤癌）风险的风险比（HR）和 95%置信区间（95%CI）。使用固定效应模型和Inverse-variance 加权进行数据库特异性估计的荟萃分析。
结果
RWE 队列包括 83295 名患者，其中 10504 名患者（12.6%）接受了托法替布治疗。与 TNFi 治疗相比，托法替布治疗相关任何恶性肿瘤的主要结局与任何恶性肿瘤的加权汇总 HR 在 RWE 队列中为 1.01（95%CI 0.83，1.22），在 RCT-重复队列中为 1.17（95%CI 0.85，1.62）（与 ORAL Surveillance 试验 HR 为 1.48 [95%CI 1.04，2.09]）。
结论
我们没有发现与 TNFi 治疗相比，托法替布治疗会增加 RA 患者恶性肿瘤发展的风险，在真实世界环境中接受治疗。然而，我们的结果不能排除随着托法替布治疗时间的延长而增加风险的可能性。
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