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

Abstract

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 >or= 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physician's global assessment >or= 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.

Figures

Figure 1

Cumulative percentages (confidence intervals) of retreatment after discontinuation of infliximab in patients treated for ankylosing spondylitis. Retreatment depended on the duration of response to the initial treatment. Of the 42 patients, 10 had to be retreated within 12 weeks after discontinuation of infliximab infusions, 37 within 24 weeks, and 38 within 36 weeks. By week 48, 1 of the 42 patients had not needed retreatment and 41 were again receiving infliximab.

Figure 2

Kaplan-Meier analysis of time to relapse in AS patients after discontinuation of infliximab treatment. (a) Cumulative probability of relapse analyzed according to state of remission as measured by ASAS partial remission criteria at TP1. Patients were (bold line) or were not (thin line) in partial remission at TP1. (b) Cumulative probability of relapse according to state of disease activity at TP1 as indicated by a BASDAI ≥ 3 (high disease activity) (thin line) or <3 (low disease activity) (bold line). (c) Cumulative probability of relapse according to state of disease activity at TP1 as indicated by a CRP ≤ 6 mg/l (bold line; low disease activity) or >6 mg/l (thin line; increased disease activity). AS, ankylosing spondylitis; ASAS, Assessments in Ankylosing Spondylitis [working group]; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; CRP, C-reactive protein; pts., patients; TP1, time point 1 (when infliximab treatment was discontinued).