P-051 YI Establishing an Anti-Infliximab Antibody (ATI) Threshold to Predict Infliximab Durability

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Infliximab (IFX) durability in inflammatory bowel disease (IBD) patients is impacted by the presence of anti-infliximab antibodies (ATI). However a threshold level of ATI may exist below which clinical efficacy is not compromised, especially when drug concentrations are detectable. It remains unknown what that threshold is, what interventions work best and what the most appropriate strategy is to optimize durability in the face of ATI. Our study aimed to determine what ATI level and what optimization strategy best correlated with clinical durability.


A retrospective chart review was performed on IFX treated ulcerative colitis (UC) and Crohn's disease (CD) patients followed at a tertiary care IBD center who had at least one IFX drug concentration and ATI level documented as part of standard of care (mobility shift drug tolerant assay (U/mL), Prometheus Labs, San Diego, CA). All ATI positive patients were eligible and included for analysis. Primary outcome was IFX durability defined by steroid free remission and maintained on IFX at last follow up. Associations were tested using univariate analysis. Infliximab and ATI concentrations most discriminant for IFX durability were determined by receiver operating characteristic (ROC) curve.


A total of 62 patients were ATI positive of which only 16/62 (25%) were maintained on IFX in steroid free remission at time of last follow-up. The area under the curve (AUC) for ATI was 0.81 (95% CI, 0.689–0.898), and an ATI level of 9.7 U/mL had a sensitivity of 81%, specificity of 76% and a positive likelihood ratio of 3.4 for IFX durability. Significant differences between those maintained versus discontinued on IFX were: mean age (years) 26 versus 37 (P = 0.03), mean ATI level (U/mL) 7.6 versus 31 (P = 0.005), proportion of detectable IFX concentration (%) 44 versus 17 (P = 0.03), and the strategy of adjusting IFX dose and/or interval once ATI positive 50% versus 2% (P < 0.0001). There was a trend towards significance for both mean IFX level (μg/mL) 3.9 versus 1.1 (P = 0.07) and the strategy of adding an immunomodulator to IFX monotherapy (%) 19 versus 4 (P = 0.07). There was no significant difference with respect to gender, IBD subtype (CD versus UC) or disease duration. Among those patients maintained on IFX, 13/16 (81%) had repeat ATI measurement of which 11/13 (85%) converted from ATI positive to negative. The most frequent strategy associated with these patients was dose escalation in 5/13 (38%) followed by the addition of an immunomodulator in 3/13 (23%) patients. There was no change in therapy in 2 patients and 1 patient had IFX interval shortening.


An ATI level of 9.7 U/mL or less accurately predicts IFX durability. Dose escalation was the most successful strategy associated with durability and to overcome ATI. Our data suggest that discontinuation of IFX is not necessary in all patients with ATI and dose optimization is appropriate.

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