Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn's disease

Thomas D. Walters, Mi Ok Kim, Lee A. Denson, Anne M. Griffiths, Marla Dubinsky, James Markowitz, Robert Baldassano, Wallace Crandall, Joel Rosh, Marian Pfefferkorn, Anthony Otley, Melvin B. Heyman, Neal Leleiko, Susan Baker, Stephen L. Guthery, Jonathan Evans, David Ziring, Richard Kellermayer, Michael Stephens, David Mack & 10 others Maria Oliva-Hemker, Ashish S. Patel, Barbara Kirschner, Dedrick Moulton, Stanley Cohen, Sandra Kim, Chunyan Liu, Jonah Essers, Subra Kugathasan, Jeffrey S. Hyams

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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.

Original languageEnglish (US)
Pages (from-to)383-391
Number of pages9
JournalGastroenterology
Volume146
Issue number2
DOIs
StatePublished - Jan 1 2014

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Immunologic Factors
Secondary Prevention
Crohn Disease
Tumor Necrosis Factor-alpha
Therapeutics
Immunotherapy
Confidence Intervals
Adrenal Cortex Hormones
Growth
Pediatrics
Propensity Score
Gastroenterology
North America
C-Reactive Protein
Observational Studies

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Walters, T. D., Kim, M. O., Denson, L. A., Griffiths, A. M., Dubinsky, M., Markowitz, J., ... Hyams, J. S. (2014). Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn's disease. Gastroenterology, 146(2), 383-391. https://doi.org/10.1053/j.gastro.2013.10.027
Walters, Thomas D. ; Kim, Mi Ok ; Denson, Lee A. ; Griffiths, Anne M. ; Dubinsky, Marla ; Markowitz, James ; Baldassano, Robert ; Crandall, Wallace ; Rosh, Joel ; Pfefferkorn, Marian ; Otley, Anthony ; Heyman, Melvin B. ; Leleiko, Neal ; Baker, Susan ; Guthery, Stephen L. ; Evans, Jonathan ; Ziring, David ; Kellermayer, Richard ; Stephens, Michael ; Mack, David ; Oliva-Hemker, Maria ; Patel, Ashish S. ; Kirschner, Barbara ; Moulton, Dedrick ; Cohen, Stanley ; Kim, Sandra ; Liu, Chunyan ; Essers, Jonah ; Kugathasan, Subra ; Hyams, Jeffrey S. / Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn's disease. In: Gastroenterology. 2014 ; Vol. 146, No. 2. pp. 383-391.
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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.",
author = "Walters, {Thomas D.} and Kim, {Mi Ok} and Denson, {Lee A.} and Griffiths, {Anne M.} and Marla Dubinsky and James Markowitz and Robert Baldassano and Wallace Crandall and Joel Rosh and Marian Pfefferkorn and Anthony Otley and Heyman, {Melvin B.} and Neal Leleiko and Susan Baker and Guthery, {Stephen L.} and Jonathan Evans and David Ziring and Richard Kellermayer and Michael Stephens and David Mack and Maria Oliva-Hemker and Patel, {Ashish S.} and Barbara Kirschner and Dedrick Moulton and Stanley Cohen and Sandra Kim and Chunyan Liu and Jonah Essers and Subra Kugathasan and Hyams, {Jeffrey S.}",
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Walters, TD, Kim, MO, Denson, LA, Griffiths, AM, Dubinsky, M, Markowitz, J, Baldassano, R, Crandall, W, Rosh, J, Pfefferkorn, M, Otley, A, Heyman, MB, Leleiko, N, Baker, S, Guthery, SL, Evans, J, Ziring, D, Kellermayer, R, Stephens, M, Mack, D, Oliva-Hemker, M, Patel, AS, Kirschner, B, Moulton, D, Cohen, S, Kim, S, Liu, C, Essers, J, Kugathasan, S & Hyams, JS 2014, 'Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn's disease', Gastroenterology, vol. 146, no. 2, pp. 383-391. https://doi.org/10.1053/j.gastro.2013.10.027

Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn's disease. / Walters, Thomas D.; Kim, Mi Ok; Denson, Lee A.; Griffiths, Anne M.; Dubinsky, Marla; Markowitz, James; Baldassano, Robert; Crandall, Wallace; Rosh, Joel; Pfefferkorn, Marian; Otley, Anthony; Heyman, Melvin B.; Leleiko, Neal; Baker, Susan; Guthery, Stephen L.; Evans, Jonathan; Ziring, David; Kellermayer, Richard; Stephens, Michael; Mack, David; Oliva-Hemker, Maria; Patel, Ashish S.; Kirschner, Barbara; Moulton, Dedrick; Cohen, Stanley; Kim, Sandra; Liu, Chunyan; Essers, Jonah; Kugathasan, Subra; Hyams, Jeffrey S.

In: Gastroenterology, Vol. 146, No. 2, 01.01.2014, p. 383-391.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn's disease

AU - Walters, Thomas D.

AU - Kim, Mi Ok

AU - Denson, Lee A.

AU - Griffiths, Anne M.

AU - Dubinsky, Marla

AU - Markowitz, James

AU - Baldassano, Robert

AU - Crandall, Wallace

AU - Rosh, Joel

AU - Pfefferkorn, Marian

AU - Otley, Anthony

AU - Heyman, Melvin B.

AU - Leleiko, Neal

AU - Baker, Susan

AU - Guthery, Stephen L.

AU - Evans, Jonathan

AU - Ziring, David

AU - Kellermayer, Richard

AU - Stephens, Michael

AU - Mack, David

AU - Oliva-Hemker, Maria

AU - Patel, Ashish S.

AU - Kirschner, Barbara

AU - Moulton, Dedrick

AU - Cohen, Stanley

AU - Kim, Sandra

AU - Liu, Chunyan

AU - Essers, Jonah

AU - Kugathasan, Subra

AU - Hyams, Jeffrey S.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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