746 Adalimumab Concentrations Following Dose Escalation in Inflammatory Bowel Disease

Abstract

INTRODUCTION: Therapeutic drug monitoring is frequently performed for the management of inflammatory bowel disease (IBD). Adalimumab (ADA) concentrations of 12-16 ug/ml have been associated with clinical and endoscopic remission in Crohn's disease (CD) and ulcerative colitis (UC). The feasibility of achieving these concentrations following a dose escalation is unknown. We aim to determine expected rise in serum ADA concentrations in response to increased dose frequency. METHODS: Patients with an established diagnosis of IBD, on maintenance ADA therapy, and two ADA trough concentrations were included. The primary outcome was change in ADA concentration following dose escalation from every other week to weekly. Patients who had two concentrations without a dose escalation served as a control. Student's t-test was used to assess for significant differences in and between patients. Exploratory logistic regression was used to assess for clinical factors predicting the ability to achieve an ADA concentration >12 ug/ml. RESULTS: Eighty-nine patients met inclusion criteria, 71% with CD, 23% with UC, and 6% with indeterminate colitis. Thirty six percent were on concurrent immunomodulator (IMM) therapy. Among patients on every other week ADA dosing, the initial mean ADA concentration for those who went on to a dose escalation was 3.7 ug/ml versus 9.7 ug/ml in those who did not dose escalate (P < 0.001). Following dose escalation, mean ADA concentration significantly increased by 5.7 ug/mL (P < 0.0001) compared to a significant decrease of 2.5 ug/mL (P < 0.002) in those who remained on every other week dosing. This decrease was driven by IMM de-escalation (mean decrease of 1.7 ug/ml in those without IMM change, versus 5.5 ug/ml in those who stopped IMM, P < 0.1). Exploratory logistic regression analysis identified initial ADA concentration, female sex, and ADA as first biologic as predictors of achieving an ADA concentration >12 ug/ml after dose escalation. CONCLUSION: Among patients with an initial low ADA concentration, a dose escalation to weekly will increase the concentration by 5.7 ug/ml on average. Without dose escalation, cessation of IMM may decrease ADA concentrations by 5.5 ug/ml. Female sex, ADA as first biologic, and initial ADA concentration of ≥4.9 ug/ml all predicted the ability to achieve a concentration of >12 ug/ml following dose escalation. The expected concentration change after ADA dose escalation can help to guide treating physicians in determining when dose escalation is appropriate.