P045 Do Levels Matter? Maintaining Anti-TNF Class After Secondary Loss of Response to Adalimumab in Inflammatory Bowel Disease

Abstract

BACKGROUND: Anti-tumor necrosis factor (Anti-TNF) biologic therapies have evolved as a mainstay of treatment for inflammatory bowel disease (IBD). However, 10%–20% of patients are primary non-responders to anti-TNF in clinical series and up to 40% of patients lose response to treatment over time. Current guidelines suggest that treatment failure in the setting of adequate drug concentrations are due to mechanistic failure and should be switched out of the anti-TNF class. Our aim was to assess the efficacy of switching to infliximab, rather than changing out of class, in patients with secondary loss of response to adalimumab who had a therapeutic drug level. METHODS: A retrospective chart review identified patients with ulcerative colitis (UC) and Crohn's disease (CD) treated with adalimumab within the University of North Carolina Inflammatory Bowel Disease clinic between January 1, 2007 and December 31, 2017. Patients with a therapeutic adalimumab level and treatment failure and who were subsequently treated with infliximab were included in the study. RESULTS: There were a total of 16 patients with therapeutic adalimumab levels (>5 μg/mL) and no antibody formation with treatment failure. In this population, 11 of the patients had CD, 3 patients had inflammatory bowel disease undifferentiated (IBDU) and 2 had UC. Ileocolonic CD (45.5%) and penetrating disease (54.4%) were the most common phenotypes. All patients had secondary loss of response to adalimumab and 87.5% had been increased to weekly dosing. Mean adalimumab level was 9.8 ± 6.8 μg/mL prior to switching to infliximab. Thirteen patients (81.3%) achieved clinical response with infliximab at 14 weeks and of the 8 patients with endoscopic assessments, 100% achieved endoscopic remission (5 with UC/IBDU and 3 with CD). There were a total of 6 patients in a sensitivity analysis assessing therapeutic levels >7 μg/mL. All patients were female, however all other characteristics in this group were similar to those patients evaluated with a therapeutic threshold of 5 μg/mL, including the rate of clinical response at 14 weeks (83.3%). When compared to 28 patients with adalimumab levels <5 μg/mL, there was no significant difference in clinical response at 14 weeks (P = 0.692). CONCLUSION(S): Switching within class to infliximab after secondary loss of response to adalimumab with a therapeutic level achieved clinical remission at 14 weeks in 81.3% of patients, and appears to be an acceptable strategy in selected patients. Therapeutic drug levels alone are not predictive of clinical response to a second anti-TNF.