Iannone Florenzo, Tampoia Marilina, Giannini Margherita, Lopalco Giuseppe, Cantarini Luca, Villalta C Danilo, Galeazzi Mauro, Lapadula Giovanni
Interdisciplinary Department of Medicine, Rheumatology Unit, University of Bari, Italy.
Patologia Clinica, A.O. Universitaria Consorziale Policlinico, Bari, Italy.
Clin Exp Rheumatol. 2016 May-Jun;34(3):424-9. Epub 2016 Feb 9.
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.
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.
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).
Our study showed that anti-CCP levels may change during RA course, regardless of the biological drug used and the clinical response.
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。
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。
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)。
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。