Department of Rheumatology, Hiroshima Clinic, Higashi Kannon 20-16, Nishi-ku, Hiroshima, Japan.
Department of Medical Research, Hiroshima Clinic, Hiroshima, Japan.
Rheumatol Int. 2017 Dec;37(12):2079-2085. doi: 10.1007/s00296-017-3844-9. Epub 2017 Oct 14.
Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV) risk. This study aimed to analyze the effects of Tofacitinib treatment, a Janus kinase inhibitor, on atherosclerosis in patients with RA. Patients with an active RA (28-joint disease activity score-erythrocyte sedimentation rate > 3.2) despite methotrexate (MTX) treatment 12 mg/week were included in this open-label prospective study and started on Tofacitinib (10 mg/day, 5 mg twice/day). Japanese guideline does not allow high dose of MTX. All patients used a stable dosage of MTX, steroids, and statins or lipid-lowering drugs. The primary endpoint was the comparison of the carotid intima-media thickness (CIMT) at the baseline and 54 weeks after Tofa treatment. Clinical data were collected at regular visits. Forty-six patients completed this study. CIMT did not significantly change from baseline to 54 weeks (1.09 ± 0.69 and 1.08 ± 0.78 mm, p = 0.82). In 12 patients who had atherosclerosis at baseline (carotid intima-media thickness > 1.10 mm), there was a significant decrease in CIMT (0.05± 0.026 mm; p < 0.05). However, the decrease in CIMT was of limited clinical significance. Tofacitinib increased fasting total cholesterol levels from baseline to 54 weeks (216 ± 25.3 and 234 ± 28.8 mg/dL, p < 0.01). Tofacitinib affects atherosclerosis in patients with active RA The CIMT in RA patients was stable. Tofacitinib decreased the CIMT of patients who had increased CIMT at baseline. Tofacitinib reduced RA disease activity and limited vascular damage despite up-regulating cholesterol in patients with an active RA.
类风湿关节炎(RA)患者的心血管(CV)风险增加。本研究旨在分析 Janus 激酶抑制剂托法替布治疗对 RA 患者动脉粥样硬化的影响。纳入了接受甲氨蝶呤(MTX)12mg/周治疗但仍处于活动期的 RA(28 关节疾病活动评分-红细胞沉降率>3.2)患者,这些患者开始接受托法替布(10mg/天,5mg 每日两次)治疗。日本指南不允许 MTX 大剂量使用。所有患者均使用稳定剂量的 MTX、皮质类固醇和他汀类药物或降脂药物。主要终点是托法治疗后基线和 54 周时颈动脉内膜中层厚度(CIMT)的比较。临床数据在定期就诊时收集。46 例患者完成了这项研究。CIMT 从基线到 54 周没有显著变化(1.09±0.69 和 1.08±0.78mm,p=0.82)。在基线时有动脉粥样硬化(颈动脉内膜中层厚度>1.10mm)的 12 例患者中,CIMT 显著降低(0.05±0.026mm;p<0.05)。然而,CIMT 的降低具有有限的临床意义。托法替布治疗使空腹总胆固醇水平从基线到 54 周升高(216±25.3 和 234±28.8mg/dL,p<0.01)。托法替布影响活动期 RA 患者的动脉粥样硬化 RA 患者的 CIMT 稳定。托法替布降低了基线时 CIMT 增加的患者的 CIMT。托法替布降低了 RA 疾病活动度,并限制了血管损伤,尽管在活动期 RA 患者中上调了胆固醇。