Background. An effective treatment for moderately to severely active ulcerative colitis (UC) is Infliximab. However, related baseline parameters and probability of achieving endoscopic healing during induction and maintenance phase of the therapy are not known.

Methods. Data derived from ACT – 1 and ACT – 2 randomized controlled trials comprising of 484 individuals who were treated with Infliximab were analyzed. For treated individuals, the Mayo endoscopic scores (MES; range 0 – 3, with 3 being most severe inflammation) were available for weeks (W) 0 (baseline), 8, and 30. To calculate the baseline Infliximab clearance, a two-compartment population pharmacokinetic model was employed. Three multivariable logistic regression models were derived using the ACT-1 dataset. The models were then externally validated using the ACT-2 dataset for prediction of endoscopic healing (MES ≤ 1) at W8 and W30 based on baseline variables and W30 based on W8 variables. We developed an online tool to conveniently calculate the probability of achieving endoscopic healing in individuals.

Results. Baseline Infliximab clearance, stool frequency, and rectal bleeding were associated with endoscopic healing at W8 with an area under the curve (AUC) of 0.725 and 0.667 for the derivation and validation models, respectively. Baseline Infliximab clearance, stool frequency, white blood cell count, and weight were associated with achieving endoscopic healing at W30 with an AUC of 0.682 and 0.674 for the derivation and validation models, respectively. Week 8 rectal bleeding, stool frequency, white blood cell count, and albumin were associated with achieving endoscopic healing at W30 with an AUC of 0.827 and 0.780, for the derivation and validation models, respectively. Patient-level probabilities for endoscopic healing at W8 and/or W30 can be calculated using a freely available online tool at the following URL; http://premedibd.com.s3-website.ca-central-1.amazonaws.com/. An example of the predicted probability of endoscopic healing at W8 for a hypothetical UC patient starting Infliximab therapy using the online tool is provided in Figure 1.

Figure 1. Predicted probability of endoscopic healing at Week 8 in a hypothetical UC patient starting Infliximab therapy using an online tool. Based on a population pharmacokinetic model, sex and albumin are used to calculate individual clearance of Infliximab at baseline, which is then seamlessly incorporated into the prediction model together with other covariates (stool frequency and rectal bleeding) to calculate the probability of achieving endoscopic healing at Week 8.

Conclusions. Three models were developed and externally validated to determine the probability of endoscopic healing in individuals with UC during induction and/or maintenance Infliximab therapy based on Infliximab clearance, patient demographics, and disease activity measures at baseline and/or W8.