Bacquet-Deschryver H, Jouen F, Quillard M, Ménard J F, Goëb V, Lequerré T, Mejjad O, Daragon A, Tron F, Le Loët X, Vittecoq O
Department of Rheumatology, Rouen University Hospital & Inserm U905 (IFRMP 23), Institute for Biomedical Research, University of Rouen, 76031 Rouen Cedex, France.
J Clin Immunol. 2008 Sep;28(5):445-55. doi: 10.1007/s10875-008-9214-3. Epub 2008 Jun 28.
The objective of this study was to analyze the effects of 3 anti-TNFalpha agents on markers of autoimmunity in rheumatoid arthritis (RA) and spondylarthropathy (SPA) patients.
First-time anti-TNFalpha biologics (infliximab, etanercept, or adalimumab) were prescribed to 156 RA and 95 SPA (58 ankylosing spondylarthritides, 37 psoriatic arthritides). During 1-2 years of follow-up, clinical, biological [antinuclear (ANA) and anti-double-stranded (dsDNA) antibodies, rheumatoid factors (RF), and anti-cyclic citrullinated peptide (CCP) for RA], and therapeutic data were collected biannually.
ANA appeared or ANA and anti-dsDNA titers increased significantly (P < 0.001) more under infliximab than etanercept in both rheumatisms and than adalimumab in RA patients. During the 2-year follow-up, ANA appeared more in RA patients taking adalimumab than etanercept (P = 0.003), but independently of the anti-TNFalpha used; anti-dsDNA titers rarely became positive. Under etanercept or infliximab, ANA and anti-dsDNA were not influenced by the underlying pathology nor were they affected by infliximab intensification over 18 months. Only one case of cutaneous lupus was observed in a patient having IgG anti-dsDNA. The therapeutic responses were independent of ANA and anti-dsDNA titers for all rheumatisms and biologics. In RA patients, RF titers, but not anti-CCP levels, declined with the therapeutic response for all biologics.
This is the first study that has evaluated the impact of three TNFalpha blockers on ANA and anti-dsDNA antibodies in RA and SPA patients. Autoimmunity was more induced with infliximab than etanercept and to a lesser degree to adalimumab but, more importantly, this emergent autoimmunity was exceptionally associated to clinical manifestations of lupus.
本研究旨在分析3种抗TNFα药物对类风湿关节炎(RA)和脊柱关节病(SPA)患者自身免疫标志物的影响。
首次给156例RA患者和95例SPA患者(58例强直性脊柱炎、37例银屑病关节炎)使用抗TNFα生物制剂(英夫利昔单抗、依那西普或阿达木单抗)。在1至2年的随访期间,每半年收集一次临床、生物学指标(RA患者的抗核抗体(ANA)、抗双链DNA(dsDNA)抗体、类风湿因子(RF)和抗环瓜氨酸肽(CCP))以及治疗数据。
在两种风湿病中,英夫利昔单抗治疗下ANA出现或ANA和抗dsDNA滴度显著升高(P<0.001)的情况比依那西普更多,在RA患者中比阿达木单抗更多。在2年的随访中,服用阿达木单抗的RA患者中ANA出现的情况比依那西普更多(P = 0.003),但与所使用的抗TNFα药物无关;抗dsDNA滴度很少变为阳性。在依那西普或英夫利昔单抗治疗下,ANA和抗dsDNA不受基础疾病的影响,也不受18个月内英夫利昔单抗强化治疗的影响。仅在1例IgG抗dsDNA阳性的患者中观察到1例皮肤狼疮。所有风湿病和生物制剂的治疗反应均与ANA和抗dsDNA滴度无关。在RA患者中,所有生物制剂的治疗反应均使RF滴度下降,但抗CCP水平未下降。
这是第一项评估三种TNFα阻滞剂对RA和SPA患者ANA和抗dsDNA抗体影响的研究。与依那西普相比,英夫利昔单抗更易诱导自身免疫,阿达木单抗诱导程度较小,但更重要的是,这种新出现的自身免疫异常与狼疮的临床表现相关。