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17. Long term evolution and impact of immunomodulator co-treatment and withdrawal on infliximab trough levels in 223 patients with Crohn's disease

D. Drobne1, P. Bossuyt2, C. Breynaert1, N. Vande Casteele1, G. Compernolle1, M. Juergens1, V. Ballet1, I. Cleynen1, W. Wollants1, A. Gils1, P. Rutgeerts1, S. Vermeire1, G. Van Assche1

1Leuven University Hospitals, Leuven, Belgium; 2Imelda GI Clinical Research Centre, Bonheiden, Belgium

Aim: To study the influence of immunomodulator (IMM) withdrawal on clinical outcome and on infliximab trough levels (IFX TL) in patients with Crohn's disease on infliximab (IFX) maintenance therapy and to evaluate the usefulness of IFX TLs measurement when deciding to stop IMM.

Materials and Methods: 223 patients on IFX maintenance therapy were studied (158 combo IFX+IMM and 65 who received IFX monotherapy due to history of intolerance or ineffectiveness of IMM). 117/158 patients discontinued IMM after at least 6 months of combination therapy (median of 13 months). During follow-up 109 (49%) patients experienced 192 flares necessitating IFX dose optimisation (median flare-free time 34 months) and 59 (26%) patients stopped IFX (40 for loss of response and 19 for side-effects). A total of 1.055 serial IFX TLs were measured using in-house developed ELISA (mean 4.7 IFX TLs per patient). In IMM co-treated patients IFX TLs were measured before, at the time of and after withdrawal of IMMs.

Results: Combination treatment strategy resulted in higher IFX TLs overall (3.4 μg/ml) as compared to IFX monotherapy (2.5 μg/ml) (p < 0.001). After IMM withdrawal IFX TLs and CRP remained stable in the majority of patients. However, after adjustment for IFX dose optimisation (expected to increase IFX TLs) we observed that IFX TLs did decrease in a proportion of patients necessitating dose increase or interval shortenings. 16% of patients had undetectable IFX TLs shortly after stop of IMM – half of these patients had undetectable IFX TLs already at the time of withdrawal. The great majority of these patients (90%) experienced a flare. This was significantly lower (30%) in patients with detectable IFX TLs (p < 0.001) (Figure 1). In general patients who lost response to IFX more often had undetectable or low IFX TLs (49% and 72%, respectively) than patients who did not (19% and 48%, respectively). Finally, a highly significant inverse correlation was observed between CRP and IFX TLs.

Figure 1. Undetectable IFX TLs after withdrawal of IMM and disease flares.

Conclusion: After discontinuation of IMM IFX TLs generally remain stable. A proportion of patients have undetectable trough levels at the time of withdrawal of IMM. These patients are at an increased risk of dose optimisation. Therefore measuring IFX TLs before stopping IMM seems a reasonable option to help identify patients at increased risk of disease flare.