Proactive Therapeutic Concentration Monitoring of Infliximab May Improve Outcomes for Patients with Inflammatory Bowel Disease

Abstract

Background Infliximab (IFX) is effective in the treatment of inflammatory bowel disease; however, the effect is often not durable. It is unknown if proactive therapeutic concentration monitoring (TCM) of IFX improves outcomes. Methods This is a retrospective observational study examining the use of proactive TCM and titration of IFX to a target concentration for patients with inflammatory bowel disease in clinical remission at a tertiary care center. The primary aim was to describe the clinical course of patients who had proactive TCM. A secondary analysis was done to assess if this strategy was superior to the standard of care. Results Forty-eight patients were identified as having proactive TCM. Fifteen percent had an initial undetectable trough concentration. Twenty-five percent (12 of 48) of patients escalated IFX after the first proactive TCM while 15% (7 of 48) of patients de-escalated IFX therapy over the study period. A control group of 78 patients was identified. Patients who had proactive TCM had a greater probability of remaining on IFX than controls (hazard ratio, 0.3; 95% confidence interval, 0.1–0.6; log rank test; P = 0.0006). The probability of remaining on IFX was greatest for patients who achieved a trough concentration >5 μg/mL (hazard ratio, 0.03; 95% confidence interval, 0.01–0.1; P < 0.0001 versus trough <5 μg/mL). Fewer patients in the proactive TCM group stopped IFX (10% versus 31%, P = 0.009). Conclusions In this pilot observational study, proactive TCM of IFX frequently identified patients with low or undetectable trough concentrations and resulted in a greater probability of remaining on IFX.

Importance of Measuring Levels of Infliximab in Patients Treating Inflammatory Bowel Disease in a Brazilian Cohort

“…Overlapping of functional symptoms may simulate loss of response. Immunogenicity occurs in 10%-20% of individuals due to formation of antibodies against the anti-TNF drugs (1,3,16,26) . These antibodies are generally lgG type and connect to the reticulum endothelium system, accelerating the clearance of the drug and increasing the risk of loss of response and infusional reactions.…”

“…However, frequently, relapses may not be translated into clinical symptoms (10,19) . A method for evaluating drug's efficacy is necessary, such as the serum level measurement of IFX, as well as antibody research (14,26) . This method can demonstrate low levels of IFX, with negative or low ATI in some patients, who might benefit from therapy optimization, by increasing medication's dose or decreasing administration intervals (11,23) .…”

Current approaches for optimizing the benefit of biologic therapy in ulcerative colitis

“…They found that patients with infliximab trough concentration of greater than 5 μg/ml had a higher probability of remaining on infliximab (HR 0.1). At 5 years, the probability of remaining on infliximab was 86% in the group with proactive concentration monitoring compared with 52% in the group without proactive monitoring [Vaughn et al 2014]. The active UC trials 1 and 2 (ACT-1 and ACT-2) of infliximab in UC showed that a level of infliximab of 41 μg/ml at week 8 had a positive predictive value for clinical response of 80%.…”

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

“…Th e use of therapeutic drug monitoring is most commonly measured when patients lose response to therapy. Although not ready for clinical application, an alternative approach may be the use of proactive drug monitoring ( 77 ). Recent data using proactive drug monitoring (using infl iximab in the TAXIT trial) has demonstrated that in patients in remission, adjustment of drug levels that are too low and those that are too high results in a more effi cient use of the drug.…”