Increasing Infliximab Dose Based on Symptoms, Biomarkers, and Serum Drug Concentrations Does Not Increase Clinical, Endoscopic, or Corticosteroid-Free Remission in Patients With Active Luminal Crohn's Disease

A combination of infliximab and immunomodulators is the most efficacious treatment for Crohn's disease (CD). Patients have the best outcomes when their serum concentrations of these drugs are above a determined therapeutic threshold. We performed a prospective, randomized trial to determine whether therapeutic drug monitoring (TDM) to maintain serum levels of infliximab above 3 μg/mL produced higher rates of clinical and endoscopic remission than adapting dose based only on symptoms. We performed a double-blind trial in which 122 biologic-naïve adult patients with active CD (71 female, median age 29.8 years) received induction treatment with infliximab in combination with an immunosuppressant, from July 2012 through September 2015 at 27 centers in Europe. At week 14 of treatment, patients were randomly assigned (1:1:1) to 3 infliximab maintenance groups: dose increases (2 maximum) in steps of 2.5 mg/kg based on clinical symptoms and biomarker analysis and/or serum infliximab concentrations (DIS1 group); dose increase from 5 to 10 mg/kg based on the same criteria (DIS2 group); dose increase to 10 mg/kg based on clinical symptoms alone (controls). Patients' CD activity index scores, levels of C-reactive protein, fecal levels of calprotectin, and serum concentrations of infliximab were determined at baseline and at weeks 2, 4, 6, 12, and 14 of treatment, and then every 4 weeks thereafter until week 54. The primary endpoint was sustained corticosteroid-free clinical remission (CD activity index <150) from weeks 22 through 54 with no ulcers at week 54. The primary endpoint was reached by 15/45 patients (33%) in the DIS1 group, 10/37 patients (27%) in the DIS2 group, and 16/40 patients (40%) in the control group (P=.50). In a prospective randomized exploratory trial of patients with active CD, we found increasing dose of infliximab based on a combination of symptoms, biomarkers and serum drug concentrations does not lead to corticosteroid-free clinical remission in a larger proportion of patients than increasing dose based on symptoms alone. 2011-003038-14