Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands.
Clin Exp Rheumatol. 2010 Sep-Oct;28(5):661-8. Epub 2010 Oct 22.
To investigate the influence of antibody formation to TNF-α blocking agents on the clinical response in AS patients treated with infliximab (IFX), etanercept (ETA), or adalimumab (ADA), and to investigate the development of ANA, ANCA, and anti-dsDNA antibodies in association with the formation of antibodies to TNF-α blocking agents.
Consecutive AS outpatients with active disease who started treatment with IFX (n=20), ETA (n=20), or ADA (n=20) were included in this longitudinal observational study. Clinical data were collected prospectively at baseline and after 3, 6, and 12 months of anti-TNF-α treatment. At the same time points, serum samples were collected. In these samples, antibodies to TNF-α blocking agents, serum TNF-α blocker levels, and ANA, ANCA, and anti-dsDNA antibodies were measured retrospectively.
Anti-IFX, anti-ETA, and anti-ADA antibodies were induced in 20%, 0%, and 30% of patients, respectively. Although ANA, ANCA, and anti-dsDNA antibodies were detected during anti-TNF-α treatment, no significant association was found between the presence of these autoantibodies and the formation of antibodies to TNF-α blocking agents. Patients with anti-IFX or anti-ADA antibodies had significantly lower serum TNF-α blocker levels compared to patients without these antibodies. Furthermore, significant negative correlations were found between serum TNF-α blocker levels and assessments of disease activity.
This study indicates that antibody formation to IFX or ADA is related to a decrease in efficacy and early discontinuation of anti-TNF-α treatment in AS patients. Furthermore, autoantibody formation does not seem to be associated with antibody formation to TNF-α blocking agents.
探讨抗 TNF-α 拮抗剂抗体的形成对接受英夫利昔单抗(IFX)、依那西普(ETA)或阿达木单抗(ADA)治疗的 AS 患者临床应答的影响,并研究抗 TNF-α 拮抗剂抗体形成与抗核抗体(ANA)、抗中性粒细胞胞浆抗体(ANCA)和抗双链 DNA 抗体(anti-dsDNA)发展之间的关系。
本纵向观察性研究纳入了 20 例接受 IFX、20 例接受 ETA 或 20 例接受 ADA 治疗的活动性疾病的连续 AS 门诊患者。在抗 TNF-α 治疗前、治疗后 3、6 和 12 个月,前瞻性地收集临床数据。同时收集血清样本。在这些样本中, retrospectively 测量了抗 TNF-α 拮抗剂抗体、血清 TNF-α 拮抗剂水平以及 ANA、ANCA 和抗 dsDNA 抗体。
分别有 20%、0%和 30%的患者产生了抗 IFX、抗 ETA 和抗 ADA 抗体。尽管在抗 TNF-α 治疗期间检测到了 ANA、ANCA 和抗 dsDNA 抗体,但这些自身抗体的存在与抗 TNF-α 拮抗剂抗体的形成之间没有发现显著关联。与无这些抗体的患者相比,有抗 IFX 或抗 ADA 抗体的患者血清 TNF-α 拮抗剂水平显著较低。此外,还发现血清 TNF-α 拮抗剂水平与疾病活动评估之间存在显著负相关。
本研究表明,在 AS 患者中,IFX 或 ADA 抗体的形成与疗效降低和抗 TNF-α 治疗的早期停药有关。此外,自身抗体的形成似乎与抗 TNF-α 拮抗剂抗体的形成无关。