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P235. Clinical value of measuring trough levels and human anti-chimeric antibodies in patients with inflammatory bowel disease who lost response to infliximab therapy

B. Pariente1, G. Pineton de Chambrun2, M. Desroches3, C. De Cassan2, J. Gornet1, P. Desreumaux2, R. Krzysiek3, D. Emilie3, J. Colombel2, M. Allez1

1Gastroenterology department, Saint-Louis Hospital, Paris, France; 2Gastroenterology department, Claude Huriez Hospital, Lille, France; 3Immunology department, Inserm U996, Béclère Hospital, Clamart, France

Introduction: Infliximab (IFX) has been shown to be effective for the treatment of refractory inflammatory bowel disease (IBD). Despite a good initial response to IFX, up to 40% of patients will lose response over time. The clinical management of IBD patients with loss of response to IFX remains empiric.

Aim: To study the clinical value of measuring IFX trough level and human anti-chimeric antibodies (HACA) concentration in IBD patients who lost response to IFX therapy.

Patients and Methods: In a retrospective study, IBD patients with loss of response to IFX therapy and who underwent HACA and IFX concentration testing between 2008 and 2010 in two French tertiary referral centers, were included. Physicians managing patients who lost response to IFX therapy were not aware of results of IFX and HACA concentration testing.

Results: Eighty two IBD patients who lost response to IFX therapy were included. Thirty-six patients (44%) continued IFX therapy without any modification, 40 patients (49%) had an intensification of IFX therapy (defined as an increase in IFX dose or as a decrease in the frequency of infusion), 5 patients (6%) had a change to adalimumab therapy, and one patient (1%) underwent surgery. Clinical response was observed in 70% of patients with an intensification of IFX therapy and 80% of patients with a change to adalimumab as compared with 31% of patients without modification of IFX therapy (p < 0.04). In patients with an intensification of IFX therapy, IFX trough level was similar between patients with or without clinical response (3.2±3.9 and 2.3±2.19 μg/mL respectively, p > 0.3). We divided patients with an intensification of IFX therapy in quartiles regarding IFX trough level (<0.2, 0.2–1.55, 1.55–4.32 and >4.32 μg/mL). Rates of clinical response were similar in the 4 groups (67%, 73%, 70% and 70% respectively, p > 0.8). Of the 82 patients with loss of response to IFX, 18 (22%) presented detectable HACA in the serum. Positive HACA status was significantly associated with a low IFX trough level (p < 0.001). Ten HACA positive patients had an intensification of IFX therapy and 6 of these patients (60%) presented a clinical response. Seven patients with positive HACA and an intensification of IFX therapy had a second testing for HACA during the follow-up. In five of these patients (71%), HACA concentration decreased (n = 3) or HACA were no longer detectable in the serum (n = 2).

Conclusion: In patients with IBD in loss of response to IFX, clinical response to intensification of IFX therapy is not related to IFX serum concentration. Intensification of IFX therapy could be effective in patients with detectable HACA in the serum.