C-reactive protein as a predictor of low trough infliximab concentrations in patients who lose response to infliximab.

OBJECTIVE: Low serum infliximab concentrations are associated with an increased risk of loss of response in inflammatory bowel disease (IBD). The objective of this study was to evaluate the test characteristics of C-reactive protein (CRP) in identifying low serum infliximab concentrations in patients with IBD.

METHODS: We measured serum infliximab concentrations and CRP levels in patients who experienced deteriorating symptoms while on infliximab (the reactive cohort). Receiver operating characteristic (ROC) curves were used to determine the CRP concentration threshold that identified an infliximab concentration <3 μg/mL at the time of loss of response. These CRP thresholds for infliximab concentration <3 μg/mL were then tested in a separate validation cohort.

RESULTS: The reactive cohort contained 111 patients and the validation cohort contained 139 patients. In 41% of participants, serum infliximab concentration was <3 μg/mL. In the reactive cohort, the area under the ROC curve for CRP to identify an infliximab concentration <3 μg/mL was 0.70 (95% confidence interval [CI] 0.50-0.80, P = 0.02). A CRP level above 12 mg/L in the preceding 90 days provided a 90% specificity for the later detection of infliximab concentration <3 μg/mL. These test characteristics were similar in the validation cohort.

CONCLUSION: CRP levels over 12 mg/L exhibit a high specificity for identifying patients with an infliximab concentration <3 μg/mL. CRP may be cost-effective for identifying patients with low concentrations of infliximab at the time of, or at risk of, loss of response.