title: Subcutaneous Ustekinumab Provides Clinical Benefit for Two-Thirds of Patients With Crohn's Disease Refractory to Anti-Tumor Necrosis Factor Agents.
abstract: OBJECTIVE
  Ustekinumab, a human monoclonal antibody against the p40 subunit of interleukins-12 and -23, is effective in inducing and maintaining remission in patients with luminal Crohn's disease (CD). We assessed the efficacy and safety of subcutaneous ustekinumab in patients with anti-tumor necrosis factor (anti-TNF) refractory CD.
  
  
  METHODS
  We performed a retrospective observational study, collecting data from the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif on 122 consecutive patients with active CD refractory to anti-TNF therapy who received at least 1 subcutaneous injection of ustekinumab from March 2011 to December 2014, in 20 tertiary centers in Europe. Subjects were followed for at least 3 months. The primary outcome was clinical benefit, defined as reductions in symptoms and biochemical markers of CD and complete weaning from steroids, without surgery or immunosuppressant therapies.
  
  
  RESULTS
  Seventy-nine patients (65%) had a clinical benefit within 3 months of receiving ustekinumab. Concomitant immunosuppressant therapy at study inclusion increased the odds for a clinical benefit from ustekinumab (odds ratio, 5.43; 95% confidence interval, 1.14-25.77; P = .03). Over a median follow-up period of 9.8 months (interquartile range, 5.3-14.5 months), the cumulative probabilities that patients maintained the clinical benefit for 6 and 12 months after introduction of ustekinumab were 93% and 68%, respectively.
  
  
  CONCLUSIONS
  Almost two-thirds of patients with CD refractory to at least 1 anti-TNF agent receive clinical benefit from ustekinumab therapy, not requiring steroids for up to 12 months afterward. While awaiting results from ongoing trials, ustekinumab can be considered for use in these patients.
authors.affiliation: Hepato-Gastroenterology Department, Claude Huriez Hospital, University of Lille 2, Lille, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Wils
authors.affiliation: Hepato-Gastroenterology Department, Beaujon Hospital, Paris VII University, Clichy, France.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Bouhnik
authors.affiliation: Hepato-Gastroenterology Department, Lausanne University Hospital, Clinique La Source-Beaulieu, Lausanne, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Michetti
authors.affiliation: Hepato-Gastroenterology Department, Lyon Sud Hospital, Pierre-Bénite, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Flourie
authors.affiliation: Hepato-Gastroenterology Department, Robert-Debré University Hospital, Reims, France.
authors.forename: Hedia
authors.initials: H
authors.lastname: Brixi
authors.affiliation: Hepato-Gastroenterology Department, Saint-Antoine Hospital, Paris VI University, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bourrier
authors.affiliation: Hepato-Gastroenterology Department, Saint-Louis Hospital, Paris VII University, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Allez
authors.affiliation: Hepato-Gastroenterology Department, CHRU Hautepierre, Strasbourg, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Duclos
authors.affiliation: Hepato-Gastroenterology Department, North Hospital, University of Mediterranean, Marseille, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Grimaud
authors.affiliation: Hepato-Gastroenterology Department, University Hospital Estaing of Clermont-Ferrand, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Buisson
authors.affiliation: Gastroenterology Department, Henri Mondor Hospital, EC2M3, Paris Est Creteil University, Creteil, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Amiot
authors.affiliation: Hepato-Gastroenterology Department, CHU Amiens Nord, Amiens, France.
authors.forename: Mathurin
authors.initials: M
authors.lastname: Fumery
authors.affiliation: Hepato-Gastroenterology Department, University Hospital of Saint Etienne, Saint Etienne, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Roblin
authors.affiliation: Inserm U954 and Department of Gastroenterology, Nancy University Hospital, Lorraine University, Vandoeuvre-les-Nancy, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: Hepato-Gastroenterology Department, University Hospital of Nice, Nice, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Filippi
authors.affiliation: Hepato-Gastroenterology Department, University Hospital of Rennes, Rennes, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bouguen
authors.affiliation: Hepato-Gastroenterology Department, Cochin Hospital, Paris V University, Paris, France.
authors.forename: Vered
authors.initials: V
authors.lastname: Abitbol
authors.affiliation: Hepato-Gastroenterology Department, Louis Mourier Hospital, APHP, Colombes, France, University Paris VII, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Coffin
authors.affiliation: Hepato-Gastroenterology Department, Institut Mutualiste Montsouris, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Simon
authors.affiliation: Hepato-Gastroenterology Department, Haut-Leveque Hospital, University of Bordeaux II, Pessac, France.
authors.forename: David
authors.initials: D
authors.lastname: Laharie
authors.affiliation: Hepato-Gastroenterology Department, Claude Huriez Hospital, University of Lille 2, Lille, France; Inserm Unit 995, University of Lille 2, Lille, France. Electronic address: benjamin.pariente@chru-lille.fr.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pariente
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy*; D005060:Europe; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous / Q000009:adverse effects; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use; D000069549:Ustekinumab / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069549:Ustekinumab
keywords: IL12; IL23; Immunosuppressant; Inflammatory Bowel Disease