DOP75 Frequency and effectiveness of dose escalation of biologic therapy in Inflammatory Bowel Disease: The RAINBOW-IBD study of ENEIDA

Abstract

Abstract Background Despite their effectiveness in inflammatory bowel disease (IBD), biologic drugs often require dose escalation. Primary aim: To describe the frequency and effectiveness of dose escalation of biologics: infliximab (IFX), adalimumab (ADA), golimumab (GOL), vedolizumab (VED), and ustekinumab (UST). Secondary: To study the reasons for and the durability of escalation, and to identify predictive factors for relapse and for therapy discontinuation after it. Methods Adult patients from ENEIDA registry who received biologics were included. Dose escalations were specifically analysed. Survival curves assessing the impact of several variables on the durability and on clinical relapse were compared using the log-rank test. Predictive factors associated with therapy discontinuation and the risk of relapse after dose escalation were assessed by Cox-regression. Results Out of the 19,720 patients with biologics included in ENEIDA, 5,096 (26%) had their dose escalated, which were analysed. The frequency of escalation per patient-year of follow-up was: 5% (95% confidence interval [CI]=4.3-5.6%), 7% (6.3-7.7%), 7% (6.9-7.1%), 10% (9.9-10.1%), and 12% (11.9-12.1%) in patients receiving IFX, ADA, GOL, VED and UST, respectively (Figure 1). The main reason for dose escalation was loss of response (60%). Remission and clinical response were recaptured after dose escalation, respectively, in: 49% and 89% (IFX), 41% and 86% (ADA), 46% and 85% (GOL), 32% and 87% (VED), and 47% and 92% (UST). The probability of maintaining the dose escalated at 12 and 24 months was: 88% and 78% (IFX); 82% and 71% (ADA); 82% and 66% (GOL); 84% and 75% (VED); and 93% and 88% (UST), respectively (Figure 2). Predictive factors of relapse after re-achieving remission with dose escalation were: 1) IFX: previous biologic exposure (Hazard ratio [HR]=1.2, 95%CI=1.1-1.4), and IBD duration (HR=0.97, 95%CI=0.96-0.99); 2) ADA: ADA monotherapy (HR=1.2, 95%CI=1.01-1.35); 3) VED: Crohn’s disease (HR=1.56, 95%CI=1.1-2.2), and IBD duration (HR=0.9, 95%CI=0.8-0.99); and 4) UST: ulcerative colitis (HR=2.4, 95%CI=1.5-3.9). Predictive factors of therapy discontinuation after dose escalation were: 1) IFX: previous biologic exposure (HR=1.2, 95%CI=1.1-1.4), and disease duration (HR=0.98, 95%CI=0.97-0.99); 2) ADA: ADA monotherapy (HR=1.2, 95%CI=1.1-1.25); and 3) UST: ulcerative colitis (HR=1.4, 95%CI=1.1-1.9). Conclusion A proportion of IBD patients dose escalate biologics in the long-term. Dose escalation is an effective strategy to recapture response and remission. The durability of escalation seems to be relatively high over time. Prior biologic experience, IBD type, and a short evolution of IBD were identified as predictive factors of relapse and therapy discontinuation after dose escalation.