Tu1300 Mucosal Drug Concentration and Clinical Characteristics of Crohn's Disease Patients Receiving Anti-TNF Therapy

Abstract

Background: The current approach to managing loss of response to anti-TNF agents is based on clinical symptoms and empirically increasing the dose or shortening the treatment interval as opposed to tailoring the drug concentrations in individual patients.We investigated whether adalimumab drug levels (ADL) and antibodies to adalimumab (ATA) were associated with clinical and/or endoscopic remission. Methods: A cohort of patients with Crohn's disease (CD) treated with adalimumab between 2005-2013 were recruited to the study. Demographic and clinical information was obtained from chart review and patient interview. Disease activity was determined by Harvey-Bradshaw Index (HBI), ileocolonoscopy reports and CRP levels. Clinical remission was defined by HBI≤4. Endoscopic remission was defined by the absence of any ulceration in all ileocolonic segments. ADL and ATA were tested using a liquid phase assay. ATA ≤ 1 U/mL were considered low titer. Results: 91 CD patients were included in the analysis. A 59 (66%) of the patients were previously on infliximab. 48 (53%) were on doses of adalimumab greater than 40mg every other week. 28 (31%) of the patients were on concomitant immunosuppressant therapy (methotrexate or azathioprine). 58 of the patients were in clinical remission and 30 of the 58 were also in endoscopic remission. 15 (16%) subjects exhibited elevated ATA titers (>1 U/mL). 22 (24%) had any detectable ATA (> 0 U/mL). ADL levels were significantly higher in patients with low ATA compared to those with elevated ATA titers (median ADL 12.7 and 1.9 μg/mL respectively, P<0.000001) and in patients with normal CRP levels (median ADL 13.4 and 7.9 μg/mL respectively, P<0.01). Higher ADL levels were marginally associated with clinical remission alone (median ADL 11.0 and 6.7 μg/mL respectively, P=0.05), however, higher ADL drug levels were significantly associated with the combined outcome of both clinical and endoscopic remission (12.78 μg/mL vs. 7.12 μg/mL respectively, P<0.04). Conclusion: Higher adalimumab drug levels were significantly associated with the combined outcome of clinical and endoscopic remission. Higher levels were also associated with a lower antibody level and a normal CRP. Further evaluation with larger, prospective studies are required to further assess the important of drug level monitoring in this setting. However, this study suggests that achieving clinical and endoscopic remission is more likely to occur by achieving adequate adalimumab levels.