Clinical Response to Discontinuation of Anti-TNF Therapy
We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients ( n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order to assess the time to relapse (TP2). Relapse was defined as an increase to a value ≥ 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physician's global assessment ≥ 4 according to the recommendations of the Assessments in Ankylosing Spondylitis (ASAS) working group. After 52 weeks, 41 of the 42 patients (97.6%) had to be reinfused because of relapse. The mean change in the BASDAI between TP1 and TP2 was 3.6 ± 1.7 and that in the physician's global assessment was 4.4 ± 1.8 (both P < 0.001). The mean time to relapse was 17.5 weeks (± 7.9 weeks, range 7 to 45). Ten patients (24%) showed a relapse within 12 weeks and 38 patients (90.5%), within 36 weeks. After 52 weeks, only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor. Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment. Retreatment with infliximab was safe and resulted in clinical improvement in all patients to a state similar to that before the treatment was stopped. Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one.

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. 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. Persistence of clinical response was reported in long-term follow-up studies over 2 and 3 years. These results have been substantiated in studies using magnetic resonance imaging of the spine.

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.