Proactive therapeutic concentration monitoring of infliximab may improve outcomes for patients with inflammatory bowel disease: results from a pilot observational study

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.

FIGURE 1

Flow chart detailing patient selection and categorization as “proactive TCM” or “no TCM.” *Did achieve clinical remission before IFX concentration testing. *Patients achieved remission on IFX but not at the time a trough level was checked.

FIGURE 2

Duration of IFX in weeks based on a priori subgroups. A, Probability of continuing on IFX in the proactive TCM versus control groups (HR, 0.3; 95% CI, 0.1–0.6; log rank test; P = 0.0006). B, Probability of continuing IFX based on trough concentration. Log rank test for IFX trough ≥5 μg/mL (at any point in therapy) versus never achieving an IFX trough <5 mg/mL, P < 0.0001 (HR, 0.03; 95% CI, 0.001–0.1). Log rank test for IFX trough ≥5 μg/mL versus no trough testing, P < 0.0001 (HR, 0.2; 95% CI, 0.07–0.4). Log rank test for IFX trough <5 μg/mL (at any point in therapy) versus no trough testing, P = 0.6 (HR, 1.3; 95% CI, 0.5–3.3). C, Probability of continuing IFX between monotherapy with IFX and combination therapy. All had a trough concentration ≥5 μg/mL (HR, 0.6; 95% CI, 0.03–09.9; log rank test; P = 0.7).