The formation of autoantibodies and antibodies to TNF-alpha blocking agents in relation to clinical response in patients with ankylosing spondylitis

Objective To investigate the influence of antibody formation to TNF-alpha blocking agents on the clinical response in AS patients treated with infliximab (IFX), etanercept (ETA), or adalimumab (ADA), and to investigate the development of ANA, ANCA, and anti-dsDNA antibodies in association with the formation of antibodies to TNF-alpha blocking agents. Methods Consecutive AS outpatients with active disease who started treatment with IFX (n=20), ETA (n=20), or ADA (n=20) were included in this longitudinal observational study. Clinical data were collected prospectively at baseline and after 3, 6, and 12 months of anti-TNF-alpha treatment. At the same time points, serum samples were collected. In these samples, antibodies to TNF-alpha blocking agents, serum TNF-alpha blocker levels, and ANA, ANCA, and anti-dsDNA antibodies were measured retrospectively. Results Anti-IFX, anti-ETA, and anti-ADA antibodies were induced in 20%, 0%, and 30% of patients, respectively. Although ANA, ANCA, and anti-dsDNA antibodies were detected during anti-TNF-alpha treatment, no significant association was found between the presence of these autoantibodies and the formation of antibodies to TNF-alpha blocking agents. Patients with anti-IFX or anti-ADA antibodies had significantly lower serum TNF-alpha blocker levels compared to patients without these antibodies. Furthermore, significant negative correlations were found between serum TNF-alpha blocker levels and assessments of disease activity. Conclusion This study indicates that antibody formation to IFX or ADA is related to a decrease in efficacy and early discontinuation of anti-TNF-alpha treatment in AS patients. Furthermore, autoantibody formation does not seem to be associated with antibody formation to TNF-alpha blocking agents