Effects of anti-TNF-α treatment on lipid profile in patients with active rheumatoid arthritis
Effects of anti-TNF-α treatment on lipid profile in patients with active rheumatoid arthritis
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DOI：
10.1196/annals.1351.039
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发表时间：
2006-01-01
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影响因子：
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通讯作者：
Cutolo, Maurizio
中科院分区：
文献类型：
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作者：
Seriolo, Bruno;Paolino, Sabrina;Cutolo, Maurizio
类风湿性关节炎（RA）的心血管发病率和死亡率似乎增加，这可能是由于心血管疾病的危险因素，如动脉粥样硬化的加速进展的患病率增加。活动性RA患者经常表现出致动脉粥样硬化的脂质谱，这与炎症反应有关。肿瘤坏死因子-α（TNF-α），一个关键的促炎细胞因子参与RA动脉粥样硬化的发病机制，可能参与活动性RA中观察到的脂质谱改变的发展。我们的目的是研究抗TNF-α治疗联合甲氨蝶呤（MTX）和皮质类固醇治疗对活动性RA患者血脂的影响。在这项前瞻性研究中，纳入了34例连续的活动性（定义为疾病活动指数28关节评分[DAS-28]，至少为3.2）和难治性RA患者（均为女性，平均年龄51.6 ± 7.9岁，范围46-72岁），接受MTX（7.5-10 mg/周）和泼尼松（7.5- 10 mg/天）稳定治疗3个月。所有患者均接受TNF-α阻滞剂治疗（n = 16，依那西普25 mg，每周两次; n = 14，英夫利西单抗3 mg/kg，0、2、6和之后每8周一次;最后n = 4，阿达木单抗40 mg，每2周一次）。在基线、16周和24周时测量总胆固醇、高密度脂蛋白胆固醇（HDL胆固醇）、甘油三酯（TG）和脂蛋白（a）[Lp（a）]水平以及致动脉粥样硬化指数（胆固醇/HDL胆固醇比值）。结果如下：DAS-28基线为6.9 ± 2.1，16周后降至4.6 ± 1.8，24周后进一步降至4.1 ± 1.3（均P < 0.01）。抗TNF-α治疗后，基线时总胆固醇的平均水平为168 +/- 24 mg/dL，16周时增至188 +/- 28 mg/dL（P < 0.01），24周时增至197 +/- 26 mg/dL（P < 0.001）。然而，在治疗16周和24周后，HDL胆固醇的平均水平也显著高于基础值（分别为34 +/- 12 mg/dL vs 36 +/- 18 mg/dL [P < 0.05]和38 +/- 14 mg/dL [P < 0.01]）。TG、Lp（a）水平及致动脉粥样硬化指数无明显变化。有趣的是，疾病活动的变化与HDL胆固醇水平显著负相关。最后：短期抗TNF-α治疗与总胆固醇和HDL胆固醇水平的显著增加相关，并与疾病活动度降低相关。致动脉粥样硬化指数在研究期间没有变化。因此，抗TNF-α治疗可能会影响RA患者的血脂谱。
Cardiovascular morbidity and mortality appear to be increased in rheumatoid arthritis (RA), which might be due to increased prevalence of risk factors for cardiovascular disease, such as an accelerated progression of atherosclerosis. Patients with active RA frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Tumor necrosis factor-alpha (TNF-alpha), a pivotal proinflammatory cytokine implicated in the pathogenesis of atherosclerosis in RA, may be involved in the development of the altered lipid profile observed in active RA. Our aim was to investigate the effects of anti-TNF-alpha treatment in combination with methotrexate (MTX) and corticosteroid therapy on lipid profile in patients with active RA. In this prospective study 34 consecutive RA patients were included (all women, mean age 51.6 +/- 7.9 years, range 46-72 years) with active (defined as Disease Activity Index 28 joint score [DAS-28], of at least 3.2) and refractory RA, in stable treatment with MTX (7.5-10 mg/week) and prednisone (7.5-10 mg/day) for 3 months. All patients received TNF-alpha blockers (n = 16, etanercept 25 mg twice weekly; n = 14, infliximab 3 mg/kg on 0, 2, 6, and every 8 weeks thereafter; and finally, n = 4, adalimumab 40 mg every other week). Total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), triglycerides (TG) and lipoprotein (a) [Lp(a)] levels and the atherogenic index (ratio cholesterol/HDL cholesterol) were measured at base line, and at 16 and 24 weeks. Results were as follows: The DAS-28 was 6.9 +/- 2.1 at base line and decreased to 4.6 +/- 1.8 after 16 weeks, and further to 4.1 +/- 1.3 after 24 weeks (both, P < 0.01). Following anti-TNF-alpha treatment, the mean levels of total cholesterol were 168 +/- 24 mg/dL at base line and increased to 188 +/- 28 mg/dL at 16 weeks (P < 0.01), and 197 +/- 26 mg/dL at 24 weeks (P < 0.001). However, also the mean levels of HDL cholesterol were significantly higher than basal values after 16 and 24 weeks of treatment (34 +/- 12 mg/dL versus 36 +/- 18 mg/dL [P < 0.05] and 38 +/- 14 mg/dL [P < 0.01], respectively). TG and Lp(a) levels, as well as the atherogenic index were not significantly changed. Interestingly, variations in disease activity were significantly and inversely correlated with HDL cholesterol levels. In conclusion: Short anti-TNF-alpha treatment was associated with a significant increase of both total cholesterol and HDL cholesterol levels, and correlated with decreased disease activity. The atherogenic index showed no changes during the study. Therefore, anti-TNF-alpha treatment might affect lipid profile in RA patients.