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

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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Adalimumab
  • Adrenal Cortex Hormones / administration & dosage
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antibody Formation / drug effects
  • Antibody Formation / immunology
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoimmunity / drug effects*
  • Autoimmunity / immunology
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Etanercept
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Infliximab
  • Male
  • Middle Aged
  • Peptides, Cyclic / blood
  • Peptides, Cyclic / immunology
  • Receptors, Tumor Necrosis Factor / administration & dosage*
  • Severity of Illness Index
  • Spondylarthropathies / blood
  • Spondylarthropathies / drug therapy*
  • Spondylarthropathies / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Autoantibodies
  • Immunoglobulin G
  • Peptides, Cyclic
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • cyclic citrullinated peptide
  • Infliximab
  • Adalimumab
  • Etanercept