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

download Full Article (PDF file)

Lajos S. Kiss1, Barbara D. Lovasz1, Petra A. Golovics1, Zsuzsanna Vegh1, Klaudia Farkas2, Tamas Molnar2, Karoly Palatka3, Maria Papp3, Anna Mohas1, Blanka K. Szilagyi1, Szandra A. Fekete1, Michael Mandel1, Peter L. Lakatos1

1) 1st Department of Medicine, Semmelweis University, Budapest
2) 1st Department of Medicine, University of Szeged
3) 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary


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.

Key words: Crohns's disease - antinuclear antibody - double-strand DNA - anti-TNFα therapy - adverse outcome.