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类风湿关节炎患者接受不同生物药物治疗后抗环瓜氨酸肽抗体和类风湿因子各亚型血清水平的变化

Changes in anti-cyclic citrullinated peptide antibodies and rheumatoid factor isotypes serum levels in patients with rheumatoid arthritis following treatment with different biological drugs.

作者信息

Iannone Florenzo, Tampoia Marilina, Giannini Margherita, Lopalco Giuseppe, Cantarini Luca, Villalta C Danilo, Galeazzi Mauro, Lapadula Giovanni

机构信息

Interdisciplinary Department of Medicine, Rheumatology Unit, University of Bari, Italy.

Patologia Clinica, A.O. Universitaria Consorziale Policlinico, Bari, Italy.

出版信息

Clin Exp Rheumatol. 2016 May-Jun;34(3):424-9. Epub 2016 Feb 9.

Abstract

OBJECTIVES

Anti-cyclic citrullinated peptide antibodies (anti-CCP) are a serological marker of rheumatoid arthritis (RA), and also have a prognostic value for more aggressive disease. Whether anti-CCP levels may change during treatment according to clinical response is matter of debate. Likewise, it is unknown whether different biological drugs have peculiar effects on anti-CCP levels. This study aimed to investigate changes in anti-CCP serum levels in RA patients on biological drugs with different mechanism of action.

METHODS

We studied 71 patients with active RA tested positive for anti-CCP who started a first biological drug (54 anti-TNF-α drug, 9 rituximab, 8 tocilizumab). In 14 patients stopping anti-TNF-α treatment for ineffectiveness, rituximab was started. Anti-CCP and rheumatoid factor (RF) isotypes (IgM, IgA, IgG) levels were measured at entry, 12 months and again at 12 months after swapping to rituximab.

RESULTS

After 1 year of therapy of the first biological drug, patients taking anti-TNF-α drugs showed a significant reduction of the anti-CCP levels (p=0.002), and all RF isotypes (p=0.003). Also patients treated with rituximab or tolicizumab had a significant decrease in anti-CCP (p=0.01) and RF isotype levels (p=0.01). Anti-CCP levels did not correlated with DAS28 over time. In patients switching to rituximab after failure of TNF-α blockers, anti-CCP levels did not change at 12 months (p=0.06), despite of the reduction of DAS28 (p=0.02) and RFs levels (p=0.02).

CONCLUSIONS

Our study showed that anti-CCP levels may change during RA course, regardless of the biological drug used and the clinical response.

摘要

目的

抗环瓜氨酸肽抗体(抗CCP)是类风湿性关节炎(RA)的一种血清学标志物,对病情更严重的疾病也具有预后价值。抗CCP水平在治疗期间是否会根据临床反应而变化仍存在争议。同样,不同的生物药物对抗CCP水平是否有特殊影响也尚不清楚。本研究旨在调查使用不同作用机制生物药物的RA患者抗CCP血清水平的变化。

方法

我们研究了71例抗CCP检测呈阳性的活动性RA患者,这些患者开始使用第一种生物药物(54例使用抗TNF-α药物,9例使用利妥昔单抗,8例使用托珠单抗)。在14例因无效而停止抗TNF-α治疗的患者中,开始使用利妥昔单抗。在开始治疗时、12个月时以及换用利妥昔单抗后12个月再次测量抗CCP和类风湿因子(RF)各亚型(IgM、IgA、IgG)水平。

结果

第一种生物药物治疗1年后,使用抗TNF-α药物的患者抗CCP水平显著降低(p = 0.002),所有RF亚型水平也显著降低(p = 0.003)。使用利妥昔单抗或托珠单抗治疗的患者抗CCP(p = 0.01)和RF亚型水平也显著降低(p = 0.01)。抗CCP水平随时间推移与疾病活动度评分28(DAS28)无关。在TNF-α阻滞剂治疗失败后换用利妥昔单抗的患者中,抗CCP水平在12个月时未发生变化(p = 0.06),尽管DAS28降低(p = 0.02)且RF水平降低(p = 0.02)。

结论

我们的研究表明,在RA病程中抗CCP水平可能会发生变化,无论使用何种生物药物以及临床反应如何。

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