title: Association Between Low Trough Levels of Vedolizumab During Induction Therapy for Inflammatory Bowel Diseases and Need for Additional Doses Within 6 Months.
abstract: OBJECTIVE
  We investigated whether serum trough levels of vedolizumab, a humanized monoclonal antibody against integrin α4β7, during the induction phase of treatment can determine whether patients will need additional doses (optimization of therapy) within the first 6 months.
  
  
  METHODS
  We conducted an observational study of 47 consecutive patients with Crohn's disease (CD; n = 31) or ulcerative colitis (UC; n = 16) who had not responded to 2 previous treatment regimens with antagonists of tumor necrosis factor and were starting therapy with vedolizumab at 2 hospitals in France, from June 2014 through April 2016. All patients were given a 300-mg infusion of vedolizumab at the start of the study, Week 2, Week 6, and then every 8 weeks; patients were also given corticosteroids during the first 4-6 weeks. Patients not in remission at Week 6 were given additional doses of vedolizumab at Week 10 and then every 4 weeks (extended therapy or optimization). Remission at Week 6 of treatment was defined as CD activity score below 150 points for patients with CD and a partial Mayo Clinic score of <3 points, without concomitant corticosteroids, for patients with UC. Blood samples were collected each week and serum levels of vedolizumab and antibodies against vedolizumab were measured using an enzyme-linked immunosorbent assay. Median trough levels of vedolizumab and interquartile ranges were compared using the nonparametric Mann-Whitney test. The primary objective was to determine whether trough levels of vedolizumab measured during the first 6 weeks of induction therapy associated with the need for extended treatment within the first 6 months.
  
  
  RESULTS
  Based on response to therapy at Week 6, extended treatment was required for 30 of the 47 patients (23 patients with CD and 7 patients with UC). At Week 2, trough levels of vedolizumab for patients selected for extended treatment were 23.0 μg/mL (interquartile range, 14.0-37.0 μg/mL), compared with 42.5 μg/mL in patients who did not receive extended treatment (interquartile range, 33.5-50.7; P = .15). At Week 6, trough levels of vedolizumab <18.5 μg/mL were associated with need for extended therapy (100% positive predictive value, 46.2%; negative predictive value; area under the receiver operating characteristic curve, 0.72) within the first 6 months. Among patients who required extended treatment at Week 10, all of those with trough levels of vedolizumab <19.0 μg/mL at Week 6 had achieved clinical remission 4 weeks later (secondary responders).
  
  
  CONCLUSIONS
  In a prospective study of patients with CD or UC receiving induction therapy with vedolizumab, low trough levels of vedolizumab at Week 6 (<19.0 μg/mL) are associated with need for additional doses (given at Week 10 and then every 4 weeks). All patients receiving these additional doses achieved a clinical response 4 weeks later.
authors.affiliation: Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France. Electronic address: nicolas.williet@chu-st-etienne.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Williet
authors.affiliation: Department of Gastroenterology, Lyon-Sud Hospital, Hospices Civils of Lyon, Pierre Benite, France; INSERM U1111, International Center for Research in Infectiology, Lyon, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Boschetti
authors.affiliation: Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Fovet
authors.affiliation: Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Di Bernado
authors.affiliation: Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Claudez
authors.affiliation: Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Del Tedesco
authors.affiliation: Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Jarlot
authors.affiliation: Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France.
authors.forename: Leslie
authors.initials: L
authors.lastname: Rinaldi
authors.affiliation: Department of Immunology, CIC1408, EA3064 Groupe Immunité des Muqueuses et Agents Pathogènes, University Hospital of Saint Etienne, Saint-Etienne, France; EA-3064, Groupe Immunité des Muqueuses et Agents Pathogènes, Faculty of Medicine of Saint-Etienne, University of Lyon, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Berger
authors.affiliation: Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Phelip
authors.affiliation: Department of Gastroenterology, Lyon-Sud Hospital, Hospices Civils of Lyon, Pierre Benite, France; INSERM U1111, International Center for Research in Infectiology, Lyon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Flourie
authors.affiliation: Department of Gastroenterology, Lyon-Sud Hospital, Hospices Civils of Lyon, Pierre Benite, France; INSERM U1111, International Center for Research in Infectiology, Lyon, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Nancey
authors.affiliation: Department of Immunology, CIC1408, EA3064 Groupe Immunité des Muqueuses et Agents Pathogènes, University Hospital of Saint Etienne, Saint-Etienne, France; EA-3064, Groupe Immunité des Muqueuses et Agents Pathogènes, Faculty of Medicine of Saint-Etienne, University of Lyon, Lyon, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Paul
authors.affiliation: Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France; EA-3064, Groupe Immunité des Muqueuses et Agents Pathogènes, Faculty of Medicine of Saint-Etienne, University of Lyon, Lyon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Roblin
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D005602:France; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D060828:Induction Chemotherapy; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D044967:Serum / Q000737:chemistry*; D013997:Time Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005765:Gastrointestinal Agents; C543529:vedolizumab
keywords: Drug; IBD; Optimization of Treatment; Patient Management