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OP10. Importance of trough levels and antibodies on the long-term efficacy of infliximab therapy in ulcerative colitis

M.T. Arias1, N. Vande Casteele2, D. Drobne3, M. Ferrante4, I. Cleynen5, V. Ballet6, P. Rutgeerts4, A. Gils7, S. Vermeire4

1Hospital Universitario Marques De Valdecilla, Santander, Spain; 2University Hospitals Leuven, Leuven, Belgium; 3University Medical Centre Ljubljana, Gastroenterology & Hepatology, Ljubljana, Slovenia; 4University Hospital Gasthuisberg, Department of Gastroenterology, Leuven, Belgium; 5Catholic University Leuven, Gastroenterology, Leuven, Belgium; 6University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium; 7Catholic University Leuven, Department of Pharmaceutical Biology, Leuven, Belgium

Background: Infliximab (IFX) is an efficacious therapy for Crohn's disease (CD) and ulcerative colitis (UC). Recent studies in CD have proposed that trough level (TL) and antibody measurement (ATI) may help to optimize therapy but data in UC, especially correlating TL to long-term outcome of treatment, are scarce. We studied the influence of TL and ATI formation on the long-term outcome of IFX in UC.

Methods: 135 consecutive UC patients receiving induction and maintenance IFX therapy were analyzed retrospectively. TL were measured at predefined timepoints using an in-house developed ELISA. Clinical response, C‑reactive protein (CRP), serum albumin and hemoglobin were assessed at the same timepoints. ATI were measured in samples with undetectable TL.

Results: By week 10, 81% of patients responded to treatment and entered maintenance. 50% needed dose optimization for loss of response (LOR) during follow up (FU). Low IFX TL early after induction were associated with higher risk for LOR and discontinuation (p = 0.02). The ROC curve of TL at week 14 had an area under the curve of 0.672 (s.e = 0.06; p = 0.01), and a TL of 7.19 µg/mL was the cut-off value with 80% specificity and 57% sensitivity for sustained benefit. Patients with undetectable TL at least once during FU demonstrated a significantly shorter time to dose optimization (log-rank p = 0.02) and LOR (log-rank p = 0.01). An increase in TL after dose optimization was associated with restoration of response (median, [IQR] 8.7 µg/mL [3.9–17.4] vs 3.2 [0.3–16.4]; p = 0.05). In 26% patients (29) IFX was stopped for complete LOR and in 12 (11%), undetectable TL and ATI were measured at least once during FU. 58% patients were on immunomodulators (IMM) at baseline. Although concomitant IMM did not affect discontinuation rates, median TL throughout the study were higher while patients were on IMM (median, [IQR]; 10.5 µg/mL [4.4–21.0] vs 7.9 [2.4–19.8]; p = 0.02) and ATI were less frequently observed while on IMM (OR 0.6 [0.4–0.7]; p < 0.0001). Albumin, CRP and hemoglobin baseline values all correlated with TL (r = 0.152, r = −0.167, r = 0.162; p < 0.0001).

Conclusions: LOR to IFX in UC patients is associated with low TL and formation of ATI. Low TL early after induction predict future LOR. Although concomitant IMM did not affect clinical LOR rates, the TL were higher in patients on combination therapy. Longer FU will learn how important these pharmacokinetic changes may be for sustained benefit. Our data further support a role for TL monitoring in optimizing IFX therapy in IBD.