Accelerated Dosing of Infliximab Is Not Associated With Improved Colectomy Rates in Hospitalized Severe Ulcerative Colitis Patients

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Introduction: Standard infliximab doses of 5 mg/kg given at weeks 0, 2, and 6 for induction followed by maintenance doses every 8 weeks have proven effective for achieving clinical remission of ulcerative colitis. Unfortunately, during acute severe ulcerative colitis (ASUC) exacerbations, several physiologic changes occur that may accelerate infliximab clearance. The most commonly proposed mechanisms include: a high tumor necrosis factor burden, excessive fecal elimination of infliximab, and increased proteolytic degradation of infliximab by the reticuloendothelial system. Based on the pharmacokinetic properties of infliximab in ASUC, it is reasonable to expect that modified dosing strategies may be required to optimize efficacy. Strategies employed to combat a suboptimal response include decreasing the dosing interval, increasing the dose to 10 mg/kg, or both. Methods: We conducted a retrospective analysis of 41 hospitalized patients who received their first dose of infliximab for steroid-refractory ASUC at a single academic medical center from January 2010 to July 2016. Patients were categorized as having received standard induction dosing or accelerated induction dosing, which we broadly defined as any dose given 4 days earlier than standard dosing frequency, employing a 10 mg/kg per dose strategy, or both. Our primary outcome was to evaluate whether patients who received accelerated dosing had fewer colectomies at 90 days compared with patients receiving standard dosing. Results: The rate of colectomy at 90 days was lower with the standard regimen (11.1%, 2 of 18) compared with the accelerated regimen (39.1%, 9 of 23) (Fisher exact test, P=0.075). Treatment groups did not differ in measures of C-reactive protein, albumin, or hemoglobin at the time of admission or just prior to infliximab administration (Table 1). The accelerated regimen was associated with shorter time to colectomy (log-rank test, P=0.124) (Figure 1). Additionally, patients on the accelerated dosing regimen had longer hospital stays compared with those on a standard dosing regimen (14 days vs 10 days, respectively) (Wilcoxon rank-sum test, P=0.54).FigureTable: Table. Baseline CharacteristicsConclusion: In hospitalized patients with severe ulcerative colitis, an accelerated infliximab induction strategy did not decrease the need for colectomy at 90 days compared with standard dosed infliximab. While our study is limited by small numbers and heterogeneity within the accelerated dosing group, this adds to limited data in this very ill population.