Abstract
BackgroundThe threshold concentration of infliximab during maintenance therapy has not been well-defined in relation to histologic remission. The aim of the study is to dentify the maintenance-phase infliximab concentration associated with histologic remission in inflammatory bowel disease patients (IBD).MethodsA prospective cohort study was carried out in 104 IBD patients seen at a tertiary care centre in London, Canada. Infliximab trough concentrations were collected during the maintenance phase of treatment and compared between participants with and without evidence of histologic remission. Participants were additionally evaluated for sustained histologic remission, and relapse to active disease.ResultsParticipants in histologic remission attained higher mean concentrations of infliximab during the maintenance phase (10.34 ± 0.69 μg/ml) compared to those with persistent disease activity (6.23 ± 0.67 μg/ml, p-value < 0.0001). Additionally, during the maintenance phase, sustained histologic remission was also associated with a higher mean concentration of infliximab (10.81 ± 5.46 μg/ml) compared to those who relapsed to active disease (5.68 ± 3.70, p < 0.001). Overall, participants with a mean infliximab trough concentration greater than 8ug/ml were more likely to have histologic remission (area under the receiver operating characteristic curve, AUROC = 0.72, 95%CI = 0.65–0.84, p < 0.0001) and sustained histologic remission (AUC = 0.77, 95%CI = 0.63–0.91, p = 0.002).ConclusionMaintenance-phase infliximab trough concentrations greater than 8 μg/ml, which is higher than the currently recommended target concentration, are highly associated with histologic remission and sustained histologic remission.
Highlights
The threshold concentration of infliximab during maintenance therapy has not been well-defined in relation to histologic remission
American inflammatory bowel disease patients (IBD) guidelines recommend that clinicians target infliximab concentrations greater than 5ug/ml[27] Much less is known in terms of infliximab concentration targets for achieving endoscopic remission or histologic remission; according to the studies that do exist, higher infliximab concentrations are needed with increasingly stringent therapeutic targets[9, 28, 29] given the small number of studies evaluating histologic remission and infliximab trough concentrations, we aimed to evaluate the association between histologic remission and mean infliximab trough concentrations during the maintenance phase of therapy in an IBD population
Participants were excluded if they were in the induction phase of infliximab treatment, if they did not have two endoscopic assessments, if there was no available histopathology for assessment of disease activity or if there were less than three infliximab concentrations available
Summary
The threshold concentration of infliximab during maintenance therapy has not been well-defined in relation to histologic remission. The aim of the study is to dentify the maintenance-phase infliximab concentration associated with histologic remission in inflammatory bowel disease patients (IBD). Ongoing histologic disease activity, defined as persistent architectural distortions and/ or increased inflammatory infiltrates in the lamina propria or epithelium, exists in a subset of individuals with endoscopically quiescent disease [18,19,20]. This has lead many clinicians and regulatory authorities to speculate whether or not treating to mucosal healing should equate to both endoscopic and histologic remission [16, 21, 22]. Several studies, including post-hoc analyses of several key clinical trials, have confirmed that infliximab is associated with the induction of histologic remission in both CD and UC [6, 25, 26]
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