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J Clin Immunol. 2008 Sep;28(5):445-55. doi: 10.1007/s10875-008-9214-3. Epub 2008 Jun 28.

Impact of three anti-TNFalpha biologics on existing and emergent autoimmunity in rheumatoid arthritis and spondylarthropathy patients.

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Department of Rheumatology, Rouen University Hospital & Inserm U905 (IFRMP 23), Institute for Biomedical Research, University of Rouen, 76031 Rouen Cedex, France.



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.

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