Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn's disease. Issue 6 (15th July 2014)

• Record Type: Journal Article
• Authors: Mazor, Y.; Almog, R.; Kopylov, U.; Ben Hur, D.; Blatt, A.; Dahan, A.; Waterman, M.; Ben‐Horin, S.; Chowers, Y.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 40:Issue 6(2014)
• Page Start: 620
• Page End: 628
• Publication Date: 2014-07-15
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.12869
• Languages: English
• ISSNs: 0269-2813

Abstract

<abstract abstract-type="main" id="apt12869-abs-0001"> <title>Summary</title> <sec id="apt12869-sec-0001" sec-type="section"> <title>Background</title> <p>Adalimumab is an effective treatment for Crohn's disease (CD). Anti‐adalimumab antibodies (AAA) and low trough serum drug concentrations have been implicated as pre‐disposing factors for treatment failure.</p> </sec> <sec id="apt12869-sec-0002" sec-type="section"> <title>Aims</title> <p>To assess adalimumab and AAA serum levels, and to examine their association and discriminatory ability with clinical response and serum C‐reactive protein (CRP).</p> </sec> <sec id="apt12869-sec-0003" sec-type="section"> <title>Methods</title> <p>We performed a cross‐sectional study using trough sera from adalimumab‐treated CD patients. Demographical data, Montreal classification, treatment regimen and clinical status were recorded. Serum adalimumab, AAA and CRP were measured. Receiver operating characteristic analysis and a multivariate regression model were performed to find drug and antibody thresholds for predicting disease activity at time of serum sampling.</p> </sec> <sec id="apt12869-sec-0004" sec-type="section"> <title>Results</title> <p>One hundred and eighteen trough serum samples were included from 71 patients. High adalimumab trough serum concentration was associated with disease remission (Area Under Curve 0.748, <italic>P </italic>< 0.001). A cut‐off drug level of 5.85 μg/mL yielded optimal sensitivity, specificity and positive likelihood ratio for remission prediction (68%, 70.6% and 2.3, respectively). AAA were inversely related with adalimumab drug levels (Spearman's <italic>r</italic> = −0.411, <italic>P</italic> < 0.001) and when subdivided into categorical values, positively related with disease activity (<italic>P</italic> < 0.001). High drug levels and stricturing vs. penetrating or inflammatory phenotype, but not AAA levels, independently predicted disease remission in a multivariate logistic regression model.</p> </sec> <sec id="apt12869-sec-0005" sec-type="section"> <title>Conclusions</title> <p>Adalimumab drug levels were inversely related to disease activity. High levels of anti‐adalimumab antibodies were positively associated with disease activity, but this association was mediated mostly by adalimumab drug levels.</p> </sec> </abstract>