P0689 - Secondary Non-Immune Loss of Response to Long Term Maintenance Therapy with Infliximab for Inflammatory Bowel Disease Is Not Due to Inadequate Trough Levels

Michael J. Farber, BS¹, Nina Kohn, MBA, MA², Vincent Chua, BS², Keith S. Sultan, MD^3
1NYIT College of Osteopathic Medicine, Glen Head, NY; ²Northwell Health, New Hyde Park, NY; ³Northwell Health, Great Neck, NY

Introduction: Infliximab (IFX) therapy for inflammatory bowel disease (IBD) has a secondary loss of response (LOR) rate of approximately 25%, which is highest during the first year of treatment and is commonly associated with low drug trough levels, < 5 mcg/ml, and/or neutralizing antibodies to infliximab (ATI). A small subset of patients on long term therapy experience LOR without ATI and with IFX levels >5 mcg/ml. However, these accepted IFX levels are derived from observations of patients within the first year of therapy and may not be applicable to those on treatment beyond one year. We hypothesized that beyond one year of therapy, patients with non-ATI related secondary LOR and IFX levels >5 mcg/ml, may still demonstrate lower IFX troughs than those patients on long term therapy maintaining response.

Methods: A bioinformatics search was done of all adult IBD outpatients by ICD codes for Crohn’s disease (CD) or Ulcerative Colitis (UC) between 2002 and 2022. Inclusion criteria included ≥12 months of IFX use, and a least one IFX trough measurement beyond 12 months. Only patients with absent ATI and with IFX trough ≥ 5 mcg/ml were included. A chart review of each patient following drug level was conducted to determine continuation vs discontinuation of IFX and whether to confirm that discontinuation was due to a clinical LOR.

Results: A total of 167 patients met the study inclusion criteria, of whom 13 (7.8%) experienced a secondary LOR, figure 1. The mean duration of IFX use was over three years in those with and without LOR, and concurrent immunosuppressant use was low for both groups at last follow-up, table 1.The mean IFX troughs for those with LOR were numerically greater 18.5 mcg/ml vs. 13.1 mcg/ml, than for those without LOR (p =.1099), table 1.

Discussion: Non-immune secondary LOR to IFX maintained at a trough level of ≥ 5 mcg/ml beyond one year of treatment remains a rare occurrence. There is limited analysis with regard to the applicability of currently accepted IFX trough therapeutic ranges for those on treatment beyond one year. Our results did not demonstrate lower IFX levels among patients experiencing a secondary LOR on long term therapy. In fact, there was a trend towards higher trough levels for the group experiencing LOR. While the optimal trough concentration for IFX use beyond one year still needs to be defined, our results suggest that underdosing of IFX is not the cause of secondary LOR, and that other factors need to be investigated.




Disclosures:


Michael J. Farber, BS¹, Nina Kohn, MBA, MA², Vincent Chua, BS², Keith S. Sultan, MD³. P0689 - Secondary Non-Immune Loss of Response to Long Term Maintenance Therapy with Infliximab for Inflammatory Bowel Disease Is Not Due to Inadequate Trough Levels, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.