The optimal management of anti-drug antibodies to infliximab and identification of anti-drug antibody values for clinical outcomes in patients with inflammatory bowel disease.

Purpose: Secondary loss of response (LOR) to infliximab (IFX) commonly occurs. One cause is the development of anti-drug antibodies (ADAs). Evidence regarding the optimal management of ADAs is lacking. We aim to identify the best practice of management of ADAs to IFX to avoid discontinuation of therapy and to determine specific ADA cut-off values to determine pre-specified clinical outcomes.

Methods: This is a 3-year study of patients receiving IFX who developed ADAs > 8μg/ml. We reviewed the management strategies and subsequent outcomes in patients who developed ADAs.

Results: A total of 132 patients are included. Baseline characteristics include 54% male patients and mean age of 39.4 years. Fifty-two percent (n = 69) of patients discontinued IFX following the development of ADAs, 33.3% (n = 44) sited as secondary to LOR. Both an increase in IFX and adjustments to combination therapy were associated with lower rates of discontinuation of IFX vs no intervention (p value < 0.001, p value < 0.001). An increase in IFX resulted in a significant difference in ADAs/IFX trough levels pre- and post-intervention (p value < 0.001, p value = 0.032). ROC curve analysis yielded significant cut-off values for ADAs and treatment failure (ADA >16μg/ml, AUC 0.642, p value 0.003), steroid use (ADA >19 μg/ml, AUC 0.61, p value 0.048) development of infusion reactions (ADA> 37 μg/ml, AUC 0.68, p value 0.045) and switch to another biologic (ADA >45 μg/ml, AUC 0.739, p value <0.001).

Conclusion: Both escalation of IFX and combination therapy resulted in lower rates of LOR. ROC curve analysis identified significant cut-off values for ADA trough levels and important clinical outcomes.