Withdrawal of immunomodulators after co-treatment does not reduce trough level of infliximab in patients with Crohn's disease

Abstract

Background & aims: The addition of immunomodulators increases the efficacy of maintenance therapy with infliximab for up to 1 year in patients with Crohn's disease who have not been previously treated with immunomodulators. However, there are questions about the effect of withdrawing immunomodulator therapy from these patients. We studied the effects of treatment with infliximab and immunomodulators (co-treatment) and then immunomodulator withdrawal on long-term outcomes of patients, as well as trough levels of infliximab and formation of anti-infliximab antibodies (ATI).

Methods: In a retrospective study with the median follow-up period of 34 months (interquartile range, 19-58 months), we analyzed data from 223 patients treated for Crohn's disease between May 1999 and December 2010 at the University Hospitals, Leuven, Belgium (65 received infliximab monotherapy, 158 received infliximab and an immunomodulator). Trough levels of infliximab and levels of ATI were measured in blood samples collected from 117 patients throughout co-treatment, as well as the time of immunomodulator withdrawal and after withdrawal.

Results: Patients receiving co-treatment had higher trough levels of infliximab (adjusted mean increase, 1.44-fold) than those receiving infliximab monotherapy (95% confidence interval [CI], 1.07-1.92; P = .02). A smaller percentage of patients receiving co-treatment developed ATI (35 of 158, 22%) than those receiving infliximab monotherapy (25 of 65, 38%; P = .01). Among co-treated patients, levels of infliximab remained stable after immunomodulators were withdrawn (before: 3.2 μg/mL; 95% CI, 1.6-5.8 μg/mL and after: 3.7 μg/mL; 95% CI, 1.3-6.3 μg/mL; P = .70). After withdrawal of immunomodulators, 45 of 117 patients (38%) required increasing doses of infliximab, and 21 of 117 (18%) discontinued infliximab. At the time of immunomodulator withdrawal, trough levels of infliximab and C-reactive protein were most strongly associated with response to infliximab thereafter.

Conclusions: In a retrospective analysis, we confirmed that withdrawal of immunomodulators after at least 6 months (median, 13 months) of co-treatment with infliximab does not reduce the trough levels of infliximab in patients with Crohn's disease. Detectable trough levels of infliximab at the time of immunomodulator withdrawal are associated with long-term response.

Keywords: Azathioprine; Inflammatory Bowel Disease; Methotrexate; Pharmacokinetic.