A prospective cohort study to determine the relationship between serum infliximab concentration and efficacy in patients with luminal Crohn's disease

Background Patients with Crohn's disease (CD) may experience disease relapse on maintenance infliximab. Anti-drug antibodies likely contribute to loss of response, and serum infliximab levels likely correlate with efficacy. Aim To prospectively evaluate the relationship between trough serum infliximab concentration and disease activity. Methods Adult patients (N=327) with a diagnosis of CD who had received at least five consecutive infliximab infusions and who planned to receive at least two additional infusions were enrolled. The Crohn's Disease Activity Index (CDAI), serum infliximab, C-reactive protein (CRP) and antibodies-to-infliximab (ATI) were assessed at baseline, week 4 and week 8. Receiver operating characteristic (ROC) analysis examined the relationship between infliximab concentrations and disease activity. Results The mean CDAI score, which decreased 1.05 points between infusions, did not correlate with the mean change in trough infliximab concentration (+0.39 mu g/mL; r=0.099, P=0.083), but was associated with the mean change in CRP concentration (r=0.19, P<0.001). Trough infliximab concentrations below 2.8-4.6 mu g/mL best predicted a >= 70 point increase in the CDAI between infusions, and those below 2.7-2.8 mu g/mL best predicted CRP >5mg/mL at the second infusion. ATI at either visit decreased the proportion of patients with therapeutic infliximab trough levels compared with patients who were ATI negative (17.5% vs. 77.3% at visit 1 and 13.8% vs. 75.6% at visit 3; P<0.001 for both comparisons). Conclusions This prospective study confirms the relationship between trough infliximab concentrations, inflammation and antibodies-to-infliximab. Infliximab trough concentrations below 3 mu g/mL may increase the likelihood of symptoms and inflammation (ClinicalTrials.gov identifier: NCT00676988).