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在随机临床试验中用生物制剂和托法替尼治疗慢性炎症性关节炎患者的血脂谱变化:系统评价和荟萃分析。

Lipid profile changes in patients with chronic inflammatory arthritis treated with biologic agents and tofacitinib in randomized clinical trials: a systematic review and meta-analysis.

机构信息

Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain.

出版信息

Arthritis Rheumatol. 2015 Jan;67(1):117-27. doi: 10.1002/art.38894.

Abstract

OBJECTIVE

To analyze lipid changes in patients with rheumatoid arthritis (RA) and patients with spondyloarthritis (SpA) treated with biologic agents or tofacitinib in randomized clinical trials (RCTs).

METHODS

A systematic literature search was performed, using the Medline, Embase, Cochrane Library, and Web of Knowledge databases. Meta-analyses were performed using random-effects models to assess changes in the percentage of patients with abnormal lipid values or in the mean percentage of increase in the cholesterol and triglycerides levels.

RESULTS

Twenty-five of 4,527 identified articles met the inclusion criteria. Compared with RA patients treated with placebo, those treated with tocilizumab were more likely to have hypercholesterolemia (odds ratio [OR] 4.64; 95% confidence interval [95% CI] 2.71, 7.95 [P < 0.001]), increased levels of high-density lipoprotein (HDL) cholesterol (OR 2.25; 95% CI 1.14, 4.44 [P = 0.020]), and increased levels of low-density lipoprotein (LDL) cholesterol (OR 4.80; 95% CI 3.27, 7.05 [P < 0.001]); this was not observed in patients treated with tumor necrosis factor (TNF) antagonists (OR 1.54; 95% CI 0.90, 2.66 [P = 0.119]) or tofacitinib (OR 3.4; 95% CI 0.62, 18.55 [P = 0.158]). Among patients receiving tofacitinib 5 mg twice daily, the mean percentage of increases in the HDL cholesterol level (weighted mean difference [WMD] 13.00 mg/dl; 95% CI 12.08, 13.93 [P < 0.001]) and the LDL cholesterol level (WMD 11.20 mg/dl; 95% CI 10.08, 12.32 [P < 0.001]) were higher than those in the comparator groups. Among patients treated with tofacitinib 10 mg twice daily, the mean percentage of increases in the HDL cholesterol level (WMD 15.21 mg/dl; 95% CI 13.28, 17.14 [P < 0.001]) and the LDL cholesterol level (WMD 15.42 mg/dl; 95% CI 11.77, 19.06 [P < 0.001]) were also higher than those in the comparator groups. No data were available for RA treated with other biologic agents or for SpA.

CONCLUSION

In patients with RA treated with tocilizumab or tofacitinib but not with TNF antagonists, moderate changes in lipids are observed. Whether these changes pertain to the control of inflammation or to the mechanism of action of the biologic agents or tofacitinib remains undetermined.

摘要

目的

分析接受生物制剂或托法替尼治疗的类风湿关节炎(RA)和脊柱关节炎(SpA)患者的血脂变化情况,这些患者均来自随机临床试验(RCTs)。

方法

通过 Medline、Embase、Cochrane 图书馆和 Web of Knowledge 数据库进行系统文献检索。采用随机效应模型进行荟萃分析,以评估异常血脂值患者比例的变化或胆固醇和甘油三酯水平的平均百分比增加情况。

结果

在 4527 篇鉴定出的文章中,有 25 篇符合纳入标准。与接受安慰剂治疗的 RA 患者相比,接受托珠单抗治疗的患者更易发生高胆固醇血症(比值比 [OR] 4.64;95%置信区间 [95%CI] 2.71,7.95 [P<0.001])、高密度脂蛋白(HDL)胆固醇水平升高(OR 2.25;95%CI 1.14,4.44 [P=0.020])和低密度脂蛋白(LDL)胆固醇水平升高(OR 4.80;95%CI 3.27,7.05 [P<0.001]);而接受肿瘤坏死因子(TNF)拮抗剂(OR 1.54;95%CI 0.90,2.66 [P=0.119])或托法替尼(OR 3.4;95%CI 0.62,18.55 [P=0.158])治疗的患者则无此情况。接受托法替尼 5mg,每日两次治疗的患者,其 HDL 胆固醇水平(加权均数差值 [WMD] 13.00mg/dl;95%CI 12.08,13.93 [P<0.001])和 LDL 胆固醇水平(WMD 11.20mg/dl;95%CI 10.08,12.32 [P<0.001])的平均百分比增加均高于对照组。接受托法替尼 10mg,每日两次治疗的患者,其 HDL 胆固醇水平(WMD 15.21mg/dl;95%CI 13.28,17.14 [P<0.001])和 LDL 胆固醇水平(WMD 15.42mg/dl;95%CI 11.77,19.06 [P<0.001])的平均百分比增加也高于对照组。未获得 RA 患者接受其他生物制剂或 SpA 患者的数据。

结论

接受托珠单抗或托法替尼治疗但未接受 TNF 拮抗剂治疗的 RA 患者,血脂会出现中度变化。这些变化是否与炎症控制或生物制剂或托法替尼的作用机制有关,尚不清楚。

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