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

Geert D'Haens*, Severine Vermeire, Guy Lambrecht, Filip Baert, Peter Bossuyt, Benjamin Pariente, Anthony Buisson, Yoram Bouhnik, Jerome Filippi, Janneke Vander Woude, Philippe Van Hootegem, Jacques Moreau, Edouard Louis, Denis Franchimont, Martine De Vos, Fazia Mana, Laurent Peyrin-Biroulet, Hedia Brixi, Matthieu Allez, Philip CaenepeelAlexandre Aubourg, Bas Oldenburg, Marieke Pierik, Ann Gils, Sylvie Chevret, David Laharie, GETAID

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

157 Citations (Web of Science)

Abstract

BACKGROUND & AIMS: 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 mu g/mL produced higher rates of clinical and endoscopic remission than adapting dose based only on symptoms. METHODS: We performed a double-blind trial in which 122 biologic-naive 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 (dose intensification strategy [DIS] 1 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. RESULTS: The primary endpoint was reached by 15 (33%) of 45 patients in the DIS1 group, 10 (27%) of 37 patients in the DIS2 group, and 16 (40%) of 40 patients in the control group (P = .50). CONCLUSIONS: 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.
Original languageEnglish
Pages (from-to)1343-1351.e1
Number of pages10
JournalGastroenterology
Volume154
Issue number5
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Crohn's Disease
  • Therapeutic Drug Monitoring
  • Infliximab
  • Mucosal Healing
  • INFLAMMATORY-BOWEL-DISEASE
  • SCHEDULED MAINTENANCE TREATMENT
  • RANDOMIZED-TRIAL
  • TROUGH LEVEL
  • ANTIBODIES
  • THERAPY
  • INTENSIFICATION
  • MULTICENTER
  • OUTCOMES

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