Original article
Alimentary tract
Withdrawal of Immunomodulators After Co-treatment Does Not Reduce Trough Level of Infliximab in Patients With Crohn’s Disease

https://doi.org/10.1016/j.cgh.2014.07.027Get rights and content

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 Among co-treated patients, levels of infliximab remained stable after immunomodulators were withdrawn (before: 3.2 μg/mL; 95% CI, 1.6–5.8 μg/mL and after: 3.7 μg/mL; 95% CI, 1.3–6.3 μg/mL; P = .70).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.

Section snippets

Patients

In this retrospective analysis we included 223 patients with Crohn's disease who were treated with infliximab maintenance therapy12 at the University Hospitals Leuven. Serum samples were collected prospectively in all patients (Figure 1). All patients had given informed consent to the VLECC registry (biobank containing serum, DNA, and clinical characteristics of IBD patients). In our hospital, infliximab treatment is traditionally started as a combination treatment with immunomodulator except

Patient Characteristics

One hundred fifty-eight patients (71%) were co-treated with immunomodulators, and 65 patients were treated with infliximab monotherapy from the start. Immunomodulators were dosed according to the ECCO guidelines.2 One hundred seventeen of 158 patients (74%) in the combination strategy withdrew immunomodulator (85 azathioprine/6-mercaptopurine, 32 methotrexate) after a median of 13 months (IQR, 8–23) and continued infliximab monotherapy afterwards. Eighty percent of patients (126 of 158) in the

Discussion

The results of this study are in concordance with an earlier study from our group4 and indicate that withdrawal of immunomodulator after at least 6 months of combination treatment can be considered in patients with Crohn's disease treated with infliximab scheduled maintenance therapy, provided they have detectable trough levels at the time of immunomodulator withdrawal. The most striking observation in this study was the fact that none of the 27 patients with infliximab trough levels >5 μg/mL

Acknowledgments

The authors thank Jestinah Mahachie for her input to the statistical analysis.

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Conflicts of interest These authors disclose the following: David Drobne has received lecture fees and consultancy from MSD, Abbott, and Pfizer. Matthias Jürgens has received lecture fees from Schering–Plough Pharma. Marc Ferrante has received lecture fees and consultancy from MSD. Ann Gils has received lecture fees from MSD. Severine Vermeire is a member of speakers bureau for Schering-Plough. Paul Rutgeerts and Gert Van Assche have received research support and consultancy and are members of speakers bureau for Janssen and MSD. The remaining authors disclose no conflicts.

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