Levels of anti-double-strained DNA but not antinuclear antibodies are associated with treatment efficacy and adverse outcomes in Crohn's disease patients treated with anti-TNFα

J Gastrointestin Liver Dis. 2013 Jun;22(2):135-40.

Abstract

Background & aims: Treatment of Crohn's disease (CD) by infliximab (IFX) has been associated with the induction of antinuclear (ANA) and anti-double strand DNA (dsDNA) autoantibodies and in some studies the formation of dsDNA antibodies was associated with lupus-like syndromes. The aims of this study were to analyse the relationship between the development of ANA and dsDNA antibodies during anti-tumor necrosis factor (TNF)α therapy and the clinical efficacy or adverse outcome in patients with inflammatory bowel disease (IBD).

Methods: Data of 96 CD patients (age at presentation: 25.1 years, folow-up: 5 years, males/females 43/53) treated with anti-TNFα for at least one-year were analyzed. Records of a total of 198 one-year treatment cycles were collected and levels of autoantibodies were determined at induction and after one-year treatment periods.

Results: The majority of CD patients had ileocolonic (67.4%) and complicated disease (B2-B3: 72.6%) with perianal lesions (63.2%). At any time ANA or dsDNA positivity was 28.6% and 18%. Elevated level of ANA at induction or during anti-TNFα therapy was not associated with treatment efficacy or development of adverse outcomes. In contrast, treatment efficacy (dsDNA positivity no/partial response vs. remission: 68.5% vs. 31.5%, P=0.003) was inferior and adverse outcomes were more frequent in patients with dsDNA positivity during the anti-TNFα therapy in both univariate analysis and in logistic regression models (OR efficacy: 4.91, 95%CI: 1.15-20.8; OR adverse outcome: 3.81,95%CI 1.04-13.9).

Conclusions: Our data suggest that development of dsDNA during biological therapy may be associated with suboptimal treatment efficacy and adverse outcomes in CD patients.

MeSH terms

  • Adult
  • Antibodies, Antinuclear / blood*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Biomarkers / blood
  • Chi-Square Distribution
  • Crohn Disease / blood
  • Crohn Disease / diagnosis
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology
  • DNA / immunology*
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Infliximab
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Odds Ratio
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Biomarkers
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • DNA
  • Infliximab