University of Toronto and Toronto Western Hospital, Toronto, Ontario, Canada.
University of California, Los Angeles.
Arthritis Care Res (Hoboken). 2019 Oct;71(10):1387-1395. doi: 10.1002/acr.23930.
The risk of cardiovascular disease (CVD) is higher in patients with psoriatic arthritis (PsA) compared to the general population. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Because tofacitinib increases circulating lipid levels in some patients, we evaluated CVD risk factors and major adverse cardiovascular events (MACE) in patients with active PsA receiving tofacitinib 5 or 10 mg twice daily plus conventional synthetic disease-modifying antirheumatic drugs.
Data were pooled from 2 phase III studies (Efficacy and Safety of Tofacitinib in Psoriatic Arthritis [OPAL Broaden] and Tofacitinib in Patients with Psoriatic Arthritis With Inadequate Response to TNF Inhibitors [OPAL Beyond]) and 1 ongoing long-term extension (Open-Label Extension Study of Tofacitinib in Psoriatic Arthritis [OPAL Balance], data cutoff January 2017; database not locked). Outcomes included fasting lipid levels, blood pressure, hypertension-related adverse events (AEs; including hypertension, high blood pressure, and increased blood pressure), and MACE.
Overall, 783 tofacitinib-treated patients were included. Percentage increases from baseline in low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) levels ranged from 9% to 14% for tofacitinib 5 mg and 10 mg at 3 and 6 months; no meaningful changes in LDL-c:HDL-c or total cholesterol:HDL-c ratios were observed. Blood pressure remained stable for 24 months. Fifty-eight patients (7.4%) had hypertension-related AEs; none were fatal (incidence rate [IR] per 100 patient-years 4.81 [95% confidence interval (95% CI) 3.65-6.22]). Five patients (0.6%) had MACE (IR 0.24 [95% CI 0.05-0.70]); 2 were fatal.
Serum lipid level increases at month 3 following tofacitinib treatment in PsA were consistent with observations in rheumatoid arthritis and psoriasis. The IR of hypertension-related AEs and MACE was low; long-term follow-up is ongoing.
与普通人群相比，患有银屑病关节炎（PsA）的患者心血管疾病（CVD）的风险更高。托法替尼是一种用于治疗 PsA 的口服 Janus 激酶抑制剂。由于托法替尼会使一些患者的循环脂质水平升高，因此我们评估了接受每日两次 5 或 10mg 托法替尼联合常规合成疾病修饰抗风湿药物治疗的活动期 PsA 患者的 CVD 危险因素和主要不良心血管事件（MACE）。
数据来自 2 项 III 期研究（托法替尼治疗银屑病关节炎的疗效和安全性[OPAL Broaden]和托法替尼治疗对 TNF 抑制剂反应不足的银屑病关节炎患者[OPAL Beyond]）和 1 项正在进行的长期扩展研究（托法替尼治疗银屑病关节炎的开放性扩展研究[OPAL Balance]，数据截止日期为 2017 年 1 月；数据库未锁定）。结果包括空腹血脂水平、血压、与高血压相关的不良事件（AE；包括高血压、高血压和血压升高）和 MACE。
总体而言，共纳入 783 例托法替尼治疗患者。托法替尼 5mg 和 10mg 组在 3 个月和 6 个月时，低密度脂蛋白胆固醇（LDL-c）和高密度脂蛋白胆固醇（HDL-c）水平从基线的百分比升高范围为 9%-14%；LDL-c：HDL-c 或总胆固醇：HDL-c 比值无明显变化。24 个月内血压保持稳定。58 例患者（7.4%）出现与高血压相关的 AE；无致命病例（每 100 患者年发生率[IR]为 4.81[95%置信区间（95%CI）为 3.65-6.22]）。5 例患者（0.6%）发生 MACE（IR 0.24[95%CI 0.05-0.70]）；其中 2 例为致命病例。
托法替尼治疗 PsA 后 3 个月时血清脂质水平升高与类风湿关节炎和银屑病中的观察结果一致。与高血压相关的 AE 和 MACE 的 IR 较低；正在进行长期随访。
