Department of Pharmacy, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Department of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
Sci Rep. 2024 Jan 2;14(1):172. doi: 10.1038/s41598-023-50379-8.
In real-world scenarios, Janus Kinase (JAK) inhibitors are often offered to "difficult-to-treat" rheumatoid arthritis patients, quite different from those included in randomized controlled trials. Our study aimed to evaluate the influence of patient-related factors on the effectiveness and safety of JAK inhibitors in real-world clinical practice. This observational retrospective study involved rheumatoid arthritis patients who received treatment with either tofacitinib, baricitinib, upadacitinib, or filgotinib. At 12 months of treatment, reasons for and rates of JAK inhibitor treatment discontinuation were examined. Treatment retentions were analyzed through Cox proportional hazard regression models and Kaplan-Meier estimates. Patient-related factors that could influence treatment retention were evaluated for the discontinuation reasons of lack of effectiveness and adverse events. At 12 months of treatment, discontinuation rates for 189 JAK inhibitor treatments were: lack of effectiveness (24.3%), adverse events (20.6%), and other reasons (3.7%). The remaining 51.4% represents the treatment continuation rate. No patient-related factors evaluated had an influence on treatment discontinuation due to lack of effectiveness. Ae significantly increased the risk of treatment discontinuation due to adverse events (p = 0.030). In terms of age, at 12 month of treatment, discontinuation rates due to adverse events were: < 65 years, 14.4% vs. 65 years or older, 26.3% (p = 0.019). Rheumatoid arthritis patients aged 65 years or older showed an increased risk of JAK inhibitor treatment discontinuation due to adverse events. Factors not related to treatment discontinuation were: sex, rheumatoid arthritis disease duration, rheumatoid arthritis disease activity, seropositivity for rheumatoid factor, seropositivity for anti-cyclic citrullinated peptides, number of prior biologic treatments, number of prior JAK inhibitor treatments, concomitant use of glucocorticoids, and concomitant use of conventional synthetic disease-modifying antirheumatic drugs.
在实际情况下，Janus 激酶 (JAK) 抑制剂通常提供给“难治性”类风湿关节炎患者，与随机对照试验中纳入的患者不同。我们的研究旨在评估患者相关因素对真实世界临床实践中 JAK 抑制剂疗效和安全性的影响。这项观察性回顾性研究涉及接受托法替尼、巴瑞替尼、乌帕替尼或菲卓替尼治疗的类风湿关节炎患者。在治疗 12 个月时，检查了 JAK 抑制剂治疗中断的原因和停药率。通过 Cox 比例风险回归模型和 Kaplan-Meier 估计分析治疗保留率。评估了与缺乏疗效和不良事件相关的停药原因的患者相关因素，以评估其对治疗保留的影响。在治疗 12 个月时，189 例 JAK 抑制剂治疗的停药率为：缺乏疗效（24.3%）、不良事件（20.6%）和其他原因（3.7%）。其余 51.4%代表治疗持续率。评估的患者相关因素对因缺乏疗效而停药没有影响。AE 显著增加了因不良事件而停药的风险（p=0.030）。在年龄方面，在治疗 12 个月时，因不良事件而停药的比例为：<65 岁，14.4%；65 岁或以上，26.3%（p=0.019）。65 岁或以上的类风湿关节炎患者因不良事件而终止 JAK 抑制剂治疗的风险增加。与治疗无关的因素包括：性别、类风湿关节炎疾病持续时间、类风湿关节炎疾病活动度、类风湿因子阳性、抗环瓜氨酸肽抗体阳性、先前生物治疗次数、先前 JAK 抑制剂治疗次数、同时使用糖皮质激素和同时使用传统合成疾病修饰抗风湿药物。
