P426 Post-induction adalimumab drug levels predict clinical and laboratory remission at week 24 in patients with Crohn’s disease
E. Zittan*1, 2, O. B. Kelly1, B. Kabakchiev1, G. C. Nguyen1, K. Croitoru1, A. H. Steinhart1, M. S. Silverberg1
1Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Canada, 2Institute of Gastroenterology and Liver Diseases, Emek Medical Centre, Afula, Israel
We investigated whether early adalimumab drug levels (ADL) and antibodies to adalimumab (ATA) at week 4 were associated with clinical and/or laboratory remission at week 24.
A prospective, multi-visit study was performed in patients initiating treatment with adalimumab with assessment at weeks 0, 4, 12, and 24 for patients with active, moderate-to-severe luminal Crohn’s disease (CD). Eligible CD patients were described as per the Montreal classification. Baseline disease activity required a Simple Endoscopic Score for CD (SES-CD) > 7; faecal calprotectin (FC) > 300 μg/g; Harvey–Bradshaw Index (HBI) > 5; and/or C-reactive protein (CRP) > 5 µg/mL. Remission at week 24 was defined as a combination of FC < 200 μg/g and CRP < 5 µg/mL. ADL and ATA were tested using a homogeneous mobility shift assay (Prometheus) at weeks 4, 12, and 24. ATA ≤ 1 U/mL was considered low titre. Kruskal–Wallis test was used to compare continuous variables between categorical outcomes. A non-parametric ROC analysis using DeLong’s method for calculating standard errors was used to determine the capacity of ADL levels at week 4 to predict remission at week 24.
In total, 32 CD patients were included in the analysis. Amongst them, 12 (37.5%) patients were previously exposed to infliximab, and 13 (40%) patients were L1; 9 (28%) patients were L2; 10 (32%) patients were L3; 5 (15%) patients were L4. In addition, 18 (56%) of the patients were on concomitant immunosuppressant therapy (methotrexate or azathioprine). Further, 13 (46.4%) patients met criteria for remission at 24 weeks; 5 (17.2%) patients exhibited early elevated ATA titres (>1 U/mL) by week 4 and, of those, 4/5 (80%) were non-responders to adalimumab at 24 weeks. Ten (31.3%) subjects required dose escalation or withdrawal from adalimumab by week 24 because of lack of response, and they exhibited significantly higher FC (p = 0.003) and CRP (p = 0.002). ADL levels at week 4 were significantly higher in responders vs non-responders at week 24 (p = 0.006). ADL levels at week 4 were a good predictor of remission at week 24 (AUC = 0.81, 95% CI = [0.64357; 0.97865]). The best ADL cut-off at week 4 that predicts remission in week 24 was 16.2 µg/mL (92% sensitivity and 67% specificity).
Higher adalimumab drug levels at week 4 (> 16.2 µg/mL) were significantly associated with remission at week 24. Higher levels were also associated with a lower antibody level and a normal CRP. This study suggests that achieving laboratory and clinical remission is more likely to occur in those with early high adalimumab levels by week 4.
Figure 1. ADL levels at week 4 were a good predictor of remission at week 24 with (AUC = 0.81, 95%CI [0.64357; 0.97865]).