title: Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease.
abstract: OBJECTIVE
  It is important to determine the effects of immunomodulators on the ability of children to remain on infliximab therapy for Crohn's disease (durability of therapy), given the potential benefits and risks of concomitant therapy-especially with thiopurines in male patients. We investigated how immunomodulatory treatment affects the durability of infliximab therapy.
  
  
  METHODS
  We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, from January 2002 through August 2014, on 502 children with Crohn's disease who participated in a prospective multicenter study. Data were collected from patients who received at least a 3-dose induction regimen of infliximab, and their concomitant use of immunomodulators: no thiopurine or methotrexate treatment, treatment for 6 months or less during infliximab therapy, or treatment for more than 6 months during infliximab therapy.
  
  
  RESULTS
  The probabilities (± standard error) that children remained on infliximab therapy for 1 year, 3 years, and 5 years after the treatment began were 0.84 ± 0.02, 0.69 ± 0.03, and 0.60 ± 0.03, respectively. Age, sex, and disease extent or location did not affect the durability of infliximab therapy. Greater length of concomitant use of immunomodulators was associated with increased time of infliximab therapy. The probability that patients with more than 6 months of immunomodulator use remained on infliximab therapy for 5 years was 0.70 ± 0.04, compared with 0.48 ± 0.08 for patients who did not receive immunomodulators and 0.55 ± 0.06 for patients who received immunomodulators for 6 months or less (P < .001). In boys who received immunomodulators for 6 months or more after starting infliximab, the overall durability of infliximab therapy was greater among patients receiving methotrexate than thiopurine (P < .01); the probabilities that they remained on infliximab therapy for 5 years were 0.97 ± 0.03 vs 0.58 ± 0.08, respectively.
  
  
  CONCLUSIONS
  In children with Crohn's disease, concomitant treatment with an immunomodulator for more than 6 months after starting infliximab therapy increases the chances that patients will remain on infliximab. In boys, methotrexate appears to increase the durability of infliximab therapy compared with thiopurine.
authors.affiliation: Connecticut Children's Medical Center, Hartford, Connecticut.
authors.forename: Victoria
authors.initials: V
authors.lastname: Grossi
authors.affiliation: Connecticut Children's Medical Center, Hartford, Connecticut.
authors.forename: Trudy
authors.initials: T
authors.lastname: Lerer
authors.affiliation: Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Griffiths
authors.affiliation: Hasbro Children's Hospital, Providence, Rhode Island.
authors.forename: Neal
authors.initials: N
authors.lastname: LeLeiko
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Jose
authors.initials: J
authors.lastname: Cabrera
authors.affiliation: Izack Walton Killam Health Centre, Halifax, Nova Scotia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Otley
authors.affiliation: Children's Medical Center, Dayton, Ohio.
authors.forename: James
authors.initials: J
authors.lastname: Rick
authors.affiliation: Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Mack
authors.affiliation: Children's Hospital, Boston, Massachusetts.
authors.forename: Athos
authors.initials: A
authors.lastname: Bousvaros
authors.affiliation: Goryeb Children's Hospital, Morristown, New Jersey.
authors.forename: Joel
authors.initials: J
authors.lastname: Rosh
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grossman
authors.affiliation: Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Shehzaad
authors.initials: S
authors.lastname: Saeed
authors.affiliation: Cleveland Clinic, Cleveland, Ohio.
authors.forename: Marsha
authors.initials: M
authors.lastname: Kay
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Brendan
authors.initials: B
authors.lastname: Boyle
authors.affiliation: Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Maria
authors.initials: M
authors.lastname: Oliva-Hemker
authors.affiliation: Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: David
authors.initials: D
authors.lastname: Keljo
authors.affiliation: Riley Hospital for Children, Indianapolis, Indiana.
authors.forename: Marian
authors.initials: M
authors.lastname: Pfefferkorn
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: William
authors.initials: W
authors.lastname: Faubion
authors.affiliation: University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kappelman
authors.affiliation: University of Minnesota, Minnesota.
authors.forename: Boris
authors.initials: B
authors.lastname: Sudel
authors.affiliation: Cohen Children's Medical Center, New Hyde Park, New York.
authors.forename: James
authors.initials: J
authors.lastname: Markowitz
authors.affiliation: Connecticut Children's Medical Center, Hartford, Connecticut. Electronic address: jhyams@connecticutchildrens.org.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hyams
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007223:Infant; D000069285:Infliximab / Q000008:administration & dosage*; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D000069285:Infliximab
keywords: Anti–Tumor Necrosis Factor; IBD; Immunosuppressant; TNF