Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab

Ankylosing spondylitis (AS) is a chronic, immune-mediated inflammatory disease that is associated with inflammation in the sacroiliac joints, the axial skeleton, entheses, peripheral joints, the uvea, and other structures [1-3]. In randomized clinical trials, agents targeting the proinflammatory cytokine tumor necrosis factor (TNF)-α, such as the monoclonal antibody infliximab, have produced significant improvement of signs and symptoms in AS patients [4]. Persistence of clinical response was reported in long-term follow-up studies over 2 [5] and 3 years [6]. These results have been substantiated in studies using magnetic resonance imaging of the spine [7].We reasoned that it was unclear whether after 3 years of successful therapy with infliximab our patients still needed treatment. Similarly, it was unknown whether discontinuation of the infliximab would be tolerated and whether a restart would be efficacious and safe. Furthermore, nothing was known about the clinical parameters predictive of flare after discontinuation of infliximab therapy. Therefore, we decided to study these questions in our cohort, who had been treated with infliximab for the preceding 3 years [6].The AS patients included in this study had all been receiving infliximab for the preceding 3 years, having participated in the first published randomized clinical trial on this therapy in active AS [4,5,8,9]. After the initial, placebo-controlled phase of that trial, the patients entered open extension phases, in which they were treated continuously with 5 mg/kg infliximab every 6 weeks. At the end of the third year of the study (defined as time point (TP)1), all the patients (n = 43) had the opportunity to continue for another extension phase. Only one patient discontinued, because of a side effect. All the others (n = 42) were included in the present extension. In accordance with the study protocol, they gave their informed consent and agreed to discontinuation of the infliximab treatment.The study