First trough level of infliximab at week 2 predicts future outcomes of induction therapy in ulcerative colitis—results from a multicenter prospective randomized controlled trial and its post hoc analysis

Background: Infliximab (IFX) is one of the treatments of choice for corticosteroid-refractory and corticosteroid-dependent ulcerative colitis (UC). A high serum trough level of IFX (TL) is reported to be associated with sustained efficacy during maintenance treatment. As part of a phase 3 randomized controlled trial of IFX in UC, we assessed the predictive value of the first TL at week 2 for short- and long-term response. Methods: Patients received intravenous IFX 5 mg/kg or placebo at weeks 0, 2, and 6. Patients with evidence of a response by week 8 continued treatment at weeks 14 and 22. TL was measured by enzyme-linked immunosorbent assay. Post hoc analysis was then performed for TL and clinical outcomes. Results: Clinical response rate at week 8, the primary end point, was significantly higher in the IFX group than placebo (p = 0.005). The incidence of adverse events between groups was similar. Week 2 TL was significantly associated with a 14-week clinical activity index (CAI) remission. In multiple logistic regression analysis, the week 2 TL-to-CAI ratio (TL/CAI, odds ratio 8.07; 95 % confidence interval 2.84–27.07, p < 0.001) was an independent factor correlating with 14-week CAI remission. The week 2 TL and TL/CAI were also significantly associated with 30-week mucosal healing. Conclusions: IFX was confirmed to be effective and safe in this population. Our results suggest that the first TL at week 2, in combination with clinical evaluation, is useful for predicting both short- and long-term outcomes, allowing an earlier decision between continuing IFX or switching to other options.