Thomas D Walters1, Mi-Ok Kim2, Lee A Denson2, Anne M Griffiths1, Marla Dubinsky3, James Markowitz4, Robert Baldassano5, Wallace Crandall6, Joel Rosh7, Marian Pfefferkorn8, Anthony Otley9, Melvin B Heyman10, Neal LeLeiko11, Susan Baker12, Stephen L Guthery13, Jonathan Evans14, David Ziring15, Richard Kellermayer16, Michael Stephens17, David Mack18, Maria Oliva-Hemker19, Ashish S Patel20, Barbara Kirschner21, Dedrick Moulton22, Stanley Cohen23, Sandra Kim24, Chunyan Liu2, Jonah Essers25, Subra Kugathasan26, Jeffrey S Hyams27. 1. Hospital for Sick Children, Toronto, Ontario, Canada. 2. Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 3. Cedars Sinai Medical Center, Los Angeles, California. 4. Cohen Children's Medical Center, New Hyde Park, New York. 5. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 6. Nationwide Children's Hospital, Columbus, Ohio. 7. Goryeb Children's Hospital, Morristown, New Jersey. 8. Riley Children's Hospital, Indianapolis, Indiana. 9. IWK Health Centre, Halifax, Nova Scotia, Canada. 10. University of California, San Francisco, California. 11. Hasbro Children's Hospital, Providence, Rhode Island. 12. Children's Hospital of Buffalo, Buffalo, New York. 13. University of Utah and Primary Children's Medical Center, Salt Lake City, Utah. 14. Nemours Children's Clinic, Jacksonville, Florida. 15. Children's Hospital of Los Angeles, Los Angeles, California. 16. Baylor College of Medicine, Houston, Texas. 17. Children's Hospital of Wisconsin, Milwaukee, Wisconsin. 18. Children's Hospital of Eastern Ontario, Ottawa, Canada. 19. Johns Hopkins Medical Center, Baltimore, Maryland. 20. Texas Children's Hospital, Dallas, Texas. 21. University of Chicago, Chicago, Illinois. 22. Vanderbilt Children's Hospital, Nashville, Tennessee. 23. Children's Healthcare, Atlanta, Georgia. 24. University of North Carolina, Chapel Hill, North Carolina. 25. Children's Hospital, Boston, Massachusetts. 26. Emory University, Atlanta, Georgia. 27. Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut. Electronic address: jhyams@connecticutchildrens.org.
Abstract
BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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: Lindsay M Griffin; Meena Thayu; Robert N Baldassano; Mark D DeBoer; Babette S Zemel; Michelle R Denburg; Lee A Denson; Justine Shults; Rita Herskovitz; Jin Long; Mary B Leonard Journal: J Clin Endocrinol Metab Date: 2015-04-28 Impact factor: 5.958