S0752 Infliximab Level <3 µg/ml Predicts Immune-Mediated Loss of Response in Patients With Crohn’s Disease

Abstract

INTRODUCTION: Therapeutic drug monitoring (TDM) is routinely used, whether proactively or reactively, for optimization of treatment of IBD patients. Infliximab (IFX) trough levels of ≥3–5 µg/ml are suggested as appropriate levels for clinical response. Patients treated with IFX can develop antibodies which can neutralize the drug, thus leading to loss of response. The aim of our study was to assess IFX trough levels that can predict immune-mediated loss of response (LOR). METHODS: This was a retrospective cohort study of Crohn’s disease (CD) patients who were exposed to IFX and had IFX trough/antibody levels (TDM) checked between 1/1/2010 and 11/31/2019. Variables assessed included demographics, smoking history, drug dose, prior anti-TNF exposure (other than IFX), IFX trough and antibody levels, IFX start and end dates, and reactive versus proactive TDM. Immune mediated LOR was defined as loss of response to IFX that was attributable to low drug levels and presence of neutralizing antibodies. Median drug levels over a patient’s total time on IFX were used for assessing immune-mediated LOR using receiver operating curve (ROC) analysis. RESULTS: A total of 333 patients with CD (median age at diagnosis 22 years, 57% men) were included. Immune-mediated LOR occurred in 16 (4.5%) patients. On univariable analysis, prior exposure to anti-TNF agents, higher median drug levels and at least 1 proactive TDM done during the patient’s disease course were associated with a lower risk of immune-mediated LOR (P = 0.04, <0.0001 and 0.002, respectively) (Table 1). On multivariable logistic regression, all three of these variables were associated with lower odds for immune mediated LOR (P = 0.04, 0.001 and 0.04, respectively) (Table 2). Furthermore, on ROC analysis, an IFX drug level cut-off value of <3.1 µg/ml had an 88% sensitivity and 83% specificity for predicting immune-mediated LOR (AUROC = 0.882, P < 0.0001) (Figure 1). CONCLUSION: Based on this study of a large cohort of CD patients, we propose that gastroenterologists should proactively target IFX trough levels >3 µg/ml in order to decrease the odds of developing immune-mediated LOR, particularly in patients that have never previously been exposed to anti-TNF alpha agents.Table 1Figure 1.: ROC curve-cutoff value of the IFX trough level in CD was calculated, as was association between IFX trough level and immune mediated loss of response, with corresponding sensitivity and specificity for CD. Cutoff value, 3.1 µg/mL; area under the ROC curve (AUROC), 88.2.