Tofacitinib improves atherosclerosis despite up-regulating serum cholesterol in patients with active rheumatoid arthritis: a cohort study
Tofacitinib improves atherosclerosis despite up-regulating serum cholesterol in patients with active rheumatoid arthritis: a cohort study
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DOI：
10.1007/s00296-017-3844-9
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发表时间：
2017-12-01
影响因子：
4
通讯作者：
Kuwaba, Noriko
中科院分区：
文献类型：
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作者：
Kume, Kensuke;Amano, Kanzo;Kuwaba, Noriko
类风湿关节炎(RA)患者患心血管疾病(CV)的风险增加。本研究旨在分析Janus激酶抑制剂托法替尼对RA患者动脉粥样硬化的影响。接受每周12毫克甲氨蝶呤(MTX)治疗的活动期类风湿性关节炎(28关节疾病活动度评分-血沉和GT；3.2)的患者被纳入这项开放式前瞻性研究，并开始服用托法替尼(每天10毫克，每天2次，每次5毫克)。日本的指南不允许大剂量的MTX。所有患者都使用了稳定剂量的MTX、类固醇、他汀类药物或降脂药物。主要终点是比较基线和Tofa治疗后54周的颈动脉内膜中层厚度(CIMT)。临床数据是在定期访问时收集的。46名患者完成了这项研究。从基线到54周，CIMT没有显著变化(1.09+/-0.69和1.08+/-0.78 mm，p=0.82)。在12例动脉粥样硬化患者中，颈动脉内膜中层厚度(1.10 mm)显著降低(0.05±-0.026 mm；p<；0.05)。然而，CIMT的降低临床意义有限。托法替尼将空腹总胆固醇水平从基线增加到54周(216+/-25.3和234+/-28.8 mg/dL，p<；0.01)。托法替尼对活动期RA患者动脉粥样硬化的影响RA患者CIMT稳定。托法替尼降低了基线时CIMT升高的患者的CIMT。托法替尼降低了类风湿性关节炎的疾病活动性和有限的血管损伤，尽管上调了活动期类风湿性关节炎患者的胆固醇。
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.