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托珠单抗对类风湿关节炎患者骨密度、血清Dickkopf-1水平及骨重塑标志物的影响。

The effect of tocilizumab on bone mineral density, serum levels of Dickkopf-1 and bone remodeling markers in patients with rheumatoid arthritis.

作者信息

Briot Karine, Rouanet Stéphanie, Schaeverbeke Thierry, Etchepare Fabien, Gaudin Philippe, Perdriger Aleth, Vray Muriel, Steinberg Ghislaine, Roux Christian

机构信息

Paris Descartes University, Department of Rheumatology, Cochin Hospital, Epidemiology and Biostatistics Unit, Sorbonne Paris Cité Research Center, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France.

Roche, 92650 Boulogne, France.

出版信息

Joint Bone Spine. 2015 Mar;82(2):109-15. doi: 10.1016/j.jbspin.2014.10.015. Epub 2014 Dec 31.

Abstract

UNLABELLED

Previous studies showed that the control of inflammation by biological therapies has a positive effect on bone in inflammatory diseases. The objective of this study was to assess the effects on bone mineral density (BMD) and bone remodeling of an anti-IL-6 monoclonal antibody (tocilizumab (TCZ)) in patients with rheumatoid arthritis (RA).

METHODS

One hundred and three patients (75% women, 52±12years) with active RA were treated with TCZ 8mg/kg + methotrexate (MTX) every 4 weeks during 48 weeks. Hip and lumbar spine BMDs were measured at baseline and after 48 weeks by dual energy X-ray absorptiometry (DXA). Pro-collagen serum type I N-terminal propeptide (PINP), serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), and serum levels of total Dickkopf-1 (Dkk-1) and sclerostin were assessed at baseline, 12 and 48 weeks.

RESULTS

BMD was available for 76 patients at baseline and at the end of the study. There was no change in lumbar spine and hip BMD over 48 weeks. Serum PINP increased from baseline by 22% (P≤0.001) and 19% (P≤0.001) at week 12 and week 48, whereas serum CTX-I remained stable. Serum DKK-1 significantly decreased from baseline by -31% (P≤0.001) and -25% (P=0.025) at week 12 and 48. Similar results were observed in the patients receiving low doses of oral corticosteroids.

CONCLUSION

In this 1-year prospective open study, patients with active RA receiving TCZ and MTX had no change in BMD, a decrease in serum DKK-1 and an increase in bone formation marker.

摘要

未标注

先前的研究表明,生物疗法对炎症的控制在炎症性疾病中对骨骼有积极影响。本研究的目的是评估抗白细胞介素-6单克隆抗体(托珠单抗(TCZ))对类风湿关节炎(RA)患者骨矿物质密度(BMD)和骨重塑的影响。

方法

103例活动性RA患者(75%为女性,年龄52±12岁)每4周接受一次8mg/kg托珠单抗(TCZ)+甲氨蝶呤(MTX)治疗,共48周。在基线和48周后通过双能X线吸收法(DXA)测量髋部和腰椎的骨密度。在基线、12周和48周时评估血清I型前胶原N端前肽(PINP)、血清I型胶原C端交联端肽(CTX-I)以及总Dickkopf-1(Dkk-1)和硬化蛋白的血清水平。

结果

76例患者在基线和研究结束时可获得骨密度数据。48周内腰椎和髋部骨密度无变化。血清PINP在第12周和第48周时较基线分别增加了22%(P≤0.001)和19%(P≤0.001),而血清CTX-I保持稳定。血清DKK-1在第12周和第48周时较基线分别显著降低了-31%(P≤0.001)和-25%(P=0.025)。在接受低剂量口服糖皮质激素的患者中也观察到了类似结果。

结论

在这项为期1年的前瞻性开放性研究中,接受托珠单抗和甲氨蝶呤治疗的活动性RA患者骨密度无变化,血清DKK-1降低,骨形成标志物增加。

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