Tu1148 Mechanisms of Loss of Response to Adalimumab in Crohn's Disease

Abstract

of this study was to assess the degree of correlation of serum ADA and ATA levels with indices of serologic and endoscopic mucosal inflammation in patients with inflammatory bowel disease (IBD). Methods: We designed a cross-sectional study including patients 18 years or older with CD or UC on treatment with ADA. Predictive variables included were demographics, disease phenotype, concurrent use of immunosuppressive drugs (mercaptopurine, azathioprine or methotrexate) and/or steroids, and random ATA/ADA levels (measured using a validated non-radiolabeled homogeneous mobility shift assay by Prometheus Laboratories [San Diego, CA]). The primary outcomes were the presence of macroscopic mucosal inflammation (MMI) during endoscopic exam and C-reactive protein (CRP) level. Results: 66 patients were included; 59 had CD. 62 (94%) and 18 (27%) of IBD patients had detectable ADA and ATA, respectively. A minimum ADA cutpoint of 5 μg/mL best predicted elevation of CRP levels (ROC: 0.71). The mean ADA level was significantly higher in patients with undetectable ATA that in those with ATA (12.5 vs 5.7 μg/mL respectively, p=0.001). Mean ADA levels were higher in patients with mucosal healing than in those patients with MMI (13.3 vs 8.5 μg/mL, respectively, p=0.02). The mean serum CRP level was significantly higher in those patients with detectable ATA than those lacking ATA (12 vs 2.1 mg/dL respectively, p=0.002). Detectable ATA was associated with ADA ,5 μg/ mL (OR 8.6 [95%CI:2.3-31.8;p,0.001], MMI (OR 3.8 [95%CI:1.1-13.2;p=0.03], need for steroids (OR 3.7 [95%CI:1.1-12.9;p=0.03], and previous infliximab use (OR 3.9 [95%CI:1.015.2;p=0.04]. When compared to those patients prescribed ADA monotherapy, patients combining ADA therapy with an immunomodulator had a higher mean level of ADA (9 vs 14 ug/mL, respectively, p=0.026). Conclusions: Among patients with IBD, serum ADA and ATA levels correlate well with both serologic and endoscopic inflammatory activity. An ADA level ≥5 μg/mL correlates well with lower CRP, and combination therapy with immunosuppressive drugs improves serologic levels of ADA. Further work establishing the role of measuring ADA and ATA levels in clinical care are warranted.