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P387. Persistence of antibodies to infliximab for more than two months strongly predicts loss of response to infliximab in inflammatory bowel diseases

M. Leclerc1, H. Marotte2, S. Paul3, E. Del Tedesco1, P. Gonzalo4, J.M. Phelip1, L. Peyrin Biroulet5, X. Roblin1, 1University Hospital, Gastroenterology, Saint Etienne, France, 2University Hospital, Rheumatology, Saint Etienne, France, 3University Hospital, Immunology, Saint Etienne, France, 4University Hospital, Biochimy, Saint Etienne, France, 5CHU de Nancy, Gastroenterologie, Vandoeuvre-les-Nancy, France

Background

Antibodies to infliximab (ATI) are frequent and may be associated with worse outcomes in Inflammatory Bowel Disease (IBD). The value of ATI (ATI threshold value, duration and kinetics) in predicting loss of response (LOR) is unknown.

Methods

We have studied, from a prospective cohort, all consecutive IBD patients treated with infliximab (IFX) who had at least 2 blood samples for ATI measurement. Non primary responders to IFX were excluded. Loss of clinical response was defined by an increase in clinical symptoms requiring a therapeutic change (IFX dose intensification, initiation of another IBD-related medication, or surgery).

Results

93 patients (mean age 30 years, sex ratio 1.2, 59 Crohn's disease, mean duration of follow up 17.2 months) were included in the study representing 481 blood samples. 32 patients (34.4%) lost clinical response during follow-up: 34 patients (38%) had normal C-reactive protein (CRP), 27 patients (30%) had positive ATI levels (14/27 only once and 13/27 more than 50% of their samples). A significant correlation was found between positive ATI level and LOR (p = 0.011) and between positive CRP level and LOR (p = 0.0003). At time of first sample, an ATI threshold >20 ng/mL predicted LOR with 94% specificity and 22% sensitivity (likelihood ratio 3.39, AUROC 0.59). Presence of positive ATI in more than 50% of one patient's samples was associated with more than 50% of LOR to IFX during follow up, and with systematic clinical relapse in case of permanent ATI (p = 0.0044). The rate of LOR increased in parallel with the number of consecutive samples positive for ATI (66.7% of LOR when at least 2 positive samples), whereas transient ATI were not associated with LOR (p = 0.01). Concomitant thiopurines, duration and dose of IFX were not associated with LOR neither with detectable ATI (permanent or transient) (p = NS). Independent predictive factors of LOR were ATI >20 ng/mL (p = 0.0071) and CRP >5 mg/L (p = 0.0046). Their association was a better predictor of treatment relapse than each one separately (relative risk of clinical remission 0.21 [CI 95 0.08–0.55] and 0.64 [CI 95 0.46–0.9] and 0.65 [CI 95 0.43–0.9] respectively for CRP >5 g/L and ATI >20 ng/mL, for ATI >20 ng/mL and finally for CRP >5 mg/mL). There was a significant inverse correlation between IFX and ATI levels; this highest association was found between IFX trough levels at time 0 and ATI levels at next infusion indicating that TRI decreases before ATI induction.

Conclusion

ATI kinetics has a strong value to predict LOR to IFX therapy. Two consecutive samples positive for ATI are associated with 66.7% of LOR whereas transient ATI were not associated with LOR. ATI and CRP levels are indepent predictors of LOR.