Combination therapy with infliximab (IFX) and an immunomodulator has been shown to be superior to IFX monotherapy for patients with inflammatory bowel disease (IBD). Presumably much of the benefit of combination therapy is decreased immunogenicity of IFX, which has been associated with secondary loss of response. IFX trough concentration testing is not routinely performed for patients who have responded to IFX. We describe our experience of optimizing IFX monotherapy through proactive measurement of IFX trough concentration and titration. In 2009, one of the authors (ASC) began proactively measuring IFX trough concentrations in patients with IBD who were in clinical remission with the intent to optimize the trough to a detectable concentration. In 2010 the goal trough concentration was changed to 5-10ug/ml. Patients on IFX monotherapy who had a trough concentration drawn over this time period with the intent of titrating to a target trough range were included. Charts were reviewed to ensure the intent of the IFX concentration was to optimize the IFX dose. Paired Wilcoxon Signed Rank test was utilized to assess for changes between initial and follow-up trough concentrations (p< 0.05 considered significant). Thirty-one patients met the criteria for" optimized monotherapy" with IFX. Crohn's disease was the predominant indication for IFX (84%). Twenty-six percent (8/31) were initially on combination therapy but deescalated to IFX monotherapy. Seven of those patients had an IFX concentration after stopping combination therapy and 4 were deemed low requiring an increase of IFX dose. Two patients developed transient low-level antibody to IFX (< 10ug/ml), with resolved after dose escalation. The median duration on IFX was 175 week (IQR: 116, 304). The median first IFX trough concentration was 6ug/ml (IQR: 3.2, 10.2). Thirty-five percent (11/31) underwent an escalation of IFX therapy after their initial trough concentration. Twenty patients had a follow-up IFX trough concentration (nine of whom underwent a dose escalation) allowing for a paired analysis. Of those patients, the median initial IFX concentration was 4.2 ug/ml compared to the follow-up concentration of 7.6 ug/ml (paired Wilcoxon Signed Rank test, p= 0.02, Figure 1). All patients were eventually titrated to an IFX trough concentration of> 3ug/ml and 83%(26/31) achieved a trough concentration of> 5ug/ml. None of the 31 patients stopped IFX therapy. Prospectively optimized monotherapy may be an alternative to combination therapy for patients with IBD on IFX. Our data suggests that patients who have routine trough concentration monitoring and dose adjustment to optimize IFX dose, can have a sustained response to IFX. This approach should be further evaluated in a prospectively controlled trial as an alternative to combination therapy for patients with IBD.