Intensified Infliximab Induction Dosing in Acute Severe Ulcerative Colitis

Abstract

Introduction: In patients with steroid-refractory, acute severe ulcerative colitis (ASUC), the optimal infliximab (IFX) induction remains unknown and practice patterns among gastroenterologists vary widely. Pharmacokinetic studies suggest that standard IFX doses may be inadequate in a high inflammatory state such as ASUC. However, data also suggests that receiving intensified IFX dosing is associated with similar 30-day colectomy rates compared to standard dosing. The aim of this study was to determine whether intensified IFX induction dosing affects colectomy rates at 1 and 6 months. Methods: A retrospective review was performed to include hospitalized patients with steroid-refractory ASUC who received rescue IFX therapy from 2008 to 2017. Patients were categorized into three groups; those who received standard dose (SD) or 5 mg/kg, double dose (DD) or a cumulative dose of 10 mg/kg within the first week, or high dose (HD) defined as a cumulative dose of greater than 10 mg/kg within the first week. The primary outcome was 1 and 6 month colectomy rates. Secondary outcomes included length of stay (LOS), time from induction to colectomy, 30-day readmission, and steroid-free remission. A composite variable defined as a subjective clinical response, colectomy-free survival at 6 months, no 30-day readmission, steroid-free remission, and persistence with IFX therapy at 6 months was also explored. Results: Forty-four patients were included, 27 (61.4%) of which were female. Eighteen (40.9%) received SD, 20 (44.4%) received DD and 6 (13.3%) received HD. The majority, 65.9% had pancolitis and 72.7% of patients were naïve to anti-TNF agents. The 1 and 6 month colectomy rates among the SD, DD and HD groups were similar (16.7%, 15%, and 16.7%, p=1.0; 33.3%, 20%, and 50% p=0.17, respectively). The rates of steroid-free remission at 6 months, time to colectomy, hospital LOS, 30-day readmission rates, persistence of IFX therapy at 30 and 60 days, and rate of initiation of a new immunosuppressant were also comparable among the three groups. The composite variable outcomes were similar among these groups<./p> Conclusion: In patients admitted with ASUC, intensified IFX induction regimens are not associated with improvement in 1 or 6 month colectomy rates. Further prospective studies are required to determine the optimal IFX dosing regimen in patients with ASUC.669 Figure 1. Summary of results