P436 Adalimumab dose escalation is effective and well tolerated in Crohn’s disease patients with secondary loss of response to adalimumab
N. Duveau*, M. Nachury, M. Boualit, R. Gerard, J. Branche, V. Maunoury, P. Desreumaux, B. Pariente
CHU de Lille, Department of Gastroenterology, Lille, France
Adalimumab (ADA) is effective in patients with luminal Crohn’s disease (CD),1 but the majority will experience a loss of response (LOR) to ADA.2 The aim of the present study was to evaluate early and sustained response to ADA dose escalation for CD patients with secondary LOR and to identify predictors of clinical response.
We performed a retrospective and observational study, including all patients who underwent an ADA dose escalation after a secondary LOR from 2007 to 2015. Response to dose escalation was defined as a significant improvement in CD-related clinical symptoms and laboratory tests assessed by the patient’s physician leading to continued ADA treatment, associated with complete weaning from steroids, without surgery or immunosuppressant introduction. Univariate and multivariate logistic regression analyses were performed to identify predictors of response to ADA dose escalation.
Included were 124 patients. Median time to dose escalation was 10 months (interquartile ranks [IQR] 4–27). ADA dose escalation was achieved by shortening interval to 40 mg every week (ewk) in 100/124 (80%) patients, and by increasing dose to 80 mg every other week (eowk) in 24/124 (19%) patients. Clinical response at 3 months was observed for 99/124 (79%) patients. In multivariate analysis, factors predicting response to ADA dose escalation at 3 months were a stricturing behaviour (OR 4.35, 95% CI 1.5–14.00; p = 0.01) and duration of ADA therapy more than 10 months before ADA LOR (OR 2.55, 95% CI 1.0–6.45; p = 0.04). At 12 months, ADA dose escalation resulted in a clinical response in 62/107 (61%) patients. In multivariate analysis, factors predicting response to ADA dose escalation at 12 months were a shortening interval to 40 mg ewk compared with 80 mg eowk (OR 3.64, 95% CI 1.28–10.37; p = 0.03) and a CRP level below than 5 mg/l at ADA dose escalation (OR 6.64, 95% CI 1.40–27.53; p = 0.01). ADA was stop after dose escalation only for 2 patients because of side effect.
In CD patients with secondary LOR, ADA dose escalation is an effective option to recapture efficacy. Stricturing behaviour, duration of ADA therapy more than 10 months before ADA LOR, shortening interval to 40 mg ewk, and normal CRP were associated with clinical response to ADA intensification.
References:  Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial, Lancet 2002;359(9317):1541–49.
 Billioud V, Sandborn WJ, Peyrin-Biroulet, et al. Loss of response and need for adalimumab dose intensification in Crohn’s disease: a systematic review, Am J Gastroenterol 2011;106:674–84.