ORIGINAL ARTICLES Predictors of Adalimumab Dose Escalation in Patients with Crohn’s Disease at a Tertiary Referral Center Russell D. Cohen, MD, Jeffrey R. Lewis, MD, Hannah Turner, Laura E. Harrell, MD, Stephen B. Hanauer, MD, and David T. Rubin, MD Background: Pivotal trials for adalimumab (ADA) demonstrated effectiveness versus placebo for induction and maintenance of remission in moderate to severely active Crohn’s disease (CD). Although the approved maintenance regimen in the U.S. is 40 mg subcutaneously every 14 days, some patients require dose-escalation ([DE] either an increase in the delivered dose or decrease in the interval of treatment). Our objective was to determine which patient-, disease-, and therapy-related factors were associated with DE in CD patients treated with ADA. Methods: This retrospective medical record review of patients included all patients treated with ADA for CD at the University of Chicago Inflammatory Bowel Disease Center between 2003 and 2008. Patient-related factors, disease-related factors, and therapy-related factors were ana- lyzed. Survival and logistic regression analyses were performed. Results: In all, 75 patients treated with ADA between December 2003 and June 2008 were identified. Thirty-one subjects (41%) required DE (32% male, median age 37.6, median disease duration 22.7 years) after a median 20 weeks of therapy (range 2–75). Patient-, clinical-, and ther- apy-related factors were similar between DE and non-DE. Need for DE was predicted by a family history of inflammatory bowel disease (IBD) (P ¼ 0.0187). Time to DE was predicted by male gender, isolated colonic disease, and smoking history (all P < 0.05); however, only male gen- der was an independent predictor of time to DE. Conclusions: In all, 41% of CD patients required ADA DE, with shorter time to DE in smokers, men, and patients with isolated colonic dis- ease. Patients, caregivers, and insurers should anticipate DE when utilizing ADA in CD. (Inflamm Bowel Dis 2012;18:10–16) Key Words: Crohn’s disease, inflammatory bowel disease, anti-TNFa therapy, adalimumab A pproximately 1.5 million people in North America suf- fer from inflammatory bowel disease (IBD), of which 650,000 have Crohn’s disease (CD). 1 In 1998 the Food and Drug Administration (FDA) approved the first biologic agent for the treatment of CD, infliximab (IFX). Production of tumor necrosis factor-a (TNF-a) is increased in IBD and is implicated in the pathogenesis of mucosal inflammation. 2 IFX, a chimeric (25% murine/75% human) IgG 1 antibody directed against TNF-a is approved for induction and main- tenance therapy of moderate to severely active CD, as well as for the treatment of fistulous disease. 3–7 However, de- spite its effectiveness, IFX use has been associated with loss of response and immunogenicity. 8 More recently, addi- tional biologic agents targeting TNF-a have been approved by the FDA, including adalimumab (ADA) and certolizu- mab pegol. ADA is a fully human, recombinant IgG 1 monoclonal antibody directed against TNF-a, approved by the FDA in 2007 for the induction and maintenance of remission of moderate to severely active CD in adult patients. 9–11 ADA is also useful in patients who have lost response to IFX. 12 Unlike IFX, which is dosed intravenously and based on body weight, ADA is administered as a subcutaneous injec- tion and has been studied and approved for uniform dosing. Despite this approved and labeled dosing, 27% of patients in the maintenance trial of ADA initially randomized to ev- ery other week dosing experienced relapse of symptoms and required weekly dosing. 11,13,14 Dose escalation rates as high as 79% have been found in CD patients receiving ADA after loss of response or intolerance to IFX. 13 How- ever, there exists a paucity of research examining factors that predict the need for this dose escalation. Given the morbidity associated with inappropriate dosing and the high cost of this biologic agent, determining predictors of dose escalation has important clinical and economic Received for publication January 10, 2011; Accepted February 15, 2011. From the Inflammatory Bowel Disease Center, University of Chicago, Chicago, Illinois. Supported in part by the American Gastroenterological Association Foundation Student Research Fellowship Award and the Digestive Disease Research Core Center of the University of Chicago (DK42086). Reprints: Russell D. Cohen, MD, Associate Professor of Medicine, Co-director, Inflammatory Bowel Disease Center, University of Chicago Medical Center, 5841 S. Maryland Ave., MC 4076, Chicago, IL 60637 (e-mail: rcohen@ medicine.bsd.uchicago.edu) Copyright V C 2011 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.21707 Published online 31 March 2011 in Wiley Online Library (wileyonlinelibrary.com). Inflamm Bowel Dis  Volume 18, Number 1, January 2012 10