title: Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn's disease.
abstract: OBJECTIVE
  Standard therapy for children newly diagnosed with Crohn's disease (CD) includes early administration of immunomodulators after initial treatment with corticosteroids. We compared the effectiveness of early (≤3 mo after diagnosis) treatment with an anti-tumor necrosis factor (TNF)α with that of an immunomodulator in attaining clinical remission and facilitating growth of pediatric patients.
  
  
  METHODS
  We analyzed data from the RISK study, an observational research program that enrolled patients younger than age 17 diagnosed with inflammatory (nonpenetrating, nonstricturing) CD from 2008 through 2012 at 28 pediatric gastroenterology centers in North America. Patients were managed by physician dictate. From 552 children (median age, 11.8 y; 61% male; 63% with pediatric CD activity index scores >30; and median C-reactive protein level 5.6-fold the upper limit of normal), we used propensity score methodology to identify 68 triads of patients matched for baseline characteristics who were treated with early anti-TNFα therapy, early immunomodulator, or no early immunotherapy. We evaluated relationships among therapies, corticosteroid and surgery-free remission (pediatric CD activity index scores, ≤10), and growth at 1 year for 204 children. Treatment after 3 months was a covariate.
  
  
  RESULTS
  Early treatment with anti-TNFα was superior to early treatment with an immunomodulator (85.3% vs 60.3% in remission; relative risk, 1.41; 95% confidence interval [CI], 1.14-1.75; P = .0017), whereas early immunomodulator therapy was no different than no early immunotherapy (60.3% vs 54.4% in remission; relative risk, 1.11; 95% CI, 0.83-1.48; P = .49) in achieving remission at 1 year. Accounting for therapy after 3 months, early treatment with anti-TNFα remained superior to early treatment with an immunomodulator (relative risk, 1.51; 95% CI, 1.20-1.89; P = .0004), whereas early immunomodulator therapy was no different than no early immunotherapy (relative risk, 1.00; 95% CI, 0.75-1.34; P = .99). The mean height z-score increased compared with baseline only in the early anti-TNFα group.
  
  
  CONCLUSIONS
  In children newly diagnosed with comparably severe CD, early monotherapy with anti-TNFα produced better overall clinical and growth outcomes at 1 year than early monotherapy with an immunomodulator. Further data will be required to best identify children most likely to benefit from early treatment with anti-TNFα therapy.
authors.affiliation: Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Walters
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Kim
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Denson
authors.affiliation: Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Griffiths
authors.affiliation: Cedars Sinai Medical Center, Los Angeles, California.
authors.forename: Marla
authors.initials: M
authors.lastname: Dubinsky
authors.affiliation: Cohen Children's Medical Center, New Hyde Park, New York.
authors.forename: James
authors.initials: J
authors.lastname: Markowitz
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Robert
authors.initials: R
authors.lastname: Baldassano
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Wallace
authors.initials: W
authors.lastname: Crandall
authors.affiliation: Goryeb Children's Hospital, Morristown, New Jersey.
authors.forename: Joel
authors.initials: J
authors.lastname: Rosh
authors.affiliation: Riley Children's Hospital, Indianapolis, Indiana.
authors.forename: Marian
authors.initials: M
authors.lastname: Pfefferkorn
authors.affiliation: IWK Health Centre, Halifax, Nova Scotia, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Otley
authors.affiliation: University of California, San Francisco, California.
authors.forename: Melvin B
authors.initials: MB
authors.lastname: Heyman
authors.affiliation: Hasbro Children's Hospital, Providence, Rhode Island.
authors.forename: Neal
authors.initials: N
authors.lastname: LeLeiko
authors.affiliation: Children's Hospital of Buffalo, Buffalo, New York.
authors.forename: Susan
authors.initials: S
authors.lastname: Baker
authors.affiliation: University of Utah and Primary Children's Medical Center, Salt Lake City, Utah.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Guthery
authors.affiliation: Nemours Children's Clinic, Jacksonville, Florida.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Evans
authors.affiliation: Children's Hospital of Los Angeles, Los Angeles, California.
authors.forename: David
authors.initials: D
authors.lastname: Ziring
authors.affiliation: Baylor College of Medicine, Houston, Texas.
authors.forename: Richard
authors.initials: R
authors.lastname: Kellermayer
authors.affiliation: Children's Hospital of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Michael
authors.initials: M
authors.lastname: Stephens
authors.affiliation: Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Mack
authors.affiliation: Johns Hopkins Medical Center, Baltimore, Maryland.
authors.forename: Maria
authors.initials: M
authors.lastname: Oliva-Hemker
authors.affiliation: Texas Children's Hospital, Dallas, Texas.
authors.forename: Ashish S
authors.initials: AS
authors.lastname: Patel
authors.affiliation: University of Chicago, Chicago, Illinois.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kirschner
authors.affiliation: Vanderbilt Children's Hospital, Nashville, Tennessee.
authors.forename: Dedrick
authors.initials: D
authors.lastname: Moulton
authors.affiliation: Children's Healthcare, Atlanta, Georgia.
authors.forename: Stanley
authors.initials: S
authors.lastname: Cohen
authors.affiliation: University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kim
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Children's Hospital, Boston, Massachusetts.
authors.forename: Jonah
authors.initials: J
authors.lastname: Essers
authors.affiliation: Emory University, Atlanta, Georgia.
authors.forename: Subra
authors.initials: S
authors.lastname: Kugathasan
authors.affiliation: Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut. Electronic address: jhyams@connecticutchildrens.org.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hyams
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D002648:Child; D002657:Child Development; D003424:Crohn Disease / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D060828:Induction Chemotherapy / Q000379:methods*; D000069285:Infliximab; D008297:Male; D016555:Matched-Pair Analysis; D015122:Mercaptopurine / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D057216:Propensity Score; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069285:Infliximab; D015122:Mercaptopurine; D000068879:Adalimumab; D001379:Azathioprine; D008727:Methotrexate
keywords: BMI; C-reactive protein; CD; CRP; CS; Crohn's disease; Drug; IM; Immune Regulation; Infliximab; PCDAI; PSA; Pediatric Crohn's Disease Activity Index; Pediatric IBD; TNF; body mass index; corticosteroid; immunomodulator; propensity scores analysis; tumor necrosis factor