Effectiveness of anti-TNFα for Crohn disease: research in a pediatric learning health system

doi:10.1542/peds.2013-4103

. 2014 Jul;134(1):37-44.

doi: 10.1542/peds.2013-4103. Epub 2014 Jun 16.

Effectiveness of anti-TNFα for Crohn disease: research in a pediatric learning health system

Christopher B Forrest¹, Wallace V Crandall², L Charles Bailey³, Peixin Zhang⁴, Marshall M Joffe⁵, Richard B Colletti⁶, Jeremy Adler⁷, Howard I Baron⁸, James Berman⁹, Fernando del Rosario¹⁰, Andrew B Grossman¹¹, Edward J Hoffenberg¹², Esther J Israel¹³, Sandra C Kim², Jenifer R Lightdale¹⁴, Peter A Margolis¹⁵, Keith Marsolo¹⁶, Devendra I Mehta¹⁷, David E Milov¹⁸, Ashish S Patel¹⁹, Jeanne Tung²⁰, Michael D Kappelman²¹

Affiliations

¹ Department of Pediatrics, andLeonard Davis Institute of Health Economics, and forrestc@email.chop.edu.
² Department of Pediatrics, The Ohio State University College of Medicine, Nationwide Children's Hospital, Columbus, Ohio;
³ Department of Pediatrics, andCenter for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
⁴ Department of Pediatrics, and.
⁵ Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
⁶ Department of Pediatrics, The University of Vermont College of Medicine, Burlington, Vermont;
⁷ Department of Pediatrics and Communicable Diseases, Division of Pediatric Gastroenterology, University of Michigan, Ann Arbor, Michigan;
⁸ Department of Pediatrics, University of Nevada School of Medicine, Pediatric Gastroenterology and Nutrition Associates, Las Vegas, Nevada;
⁹ Advocate Children's Hospital, UIC College of Medicine, Loyola University School of Medicine, Chicago, Illinois;
¹⁰ Department of Pediatrics, Division of Pediatric Gastroenterology Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware;
¹¹ Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;
¹² Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado;
¹³ Department of Pediatrics, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts;
¹⁴ Department of Medicine, Boston Children's Hospital, Boston, Massachusetts;
¹⁵ Department of Pediatrics, James M. Anderson Center for Health Systems Excellence, and.
¹⁶ Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio;
¹⁷ Department of Pediatrics, Arnold Palmer Hospital for Children, Florida State University, Orlando, Florida;
¹⁸ Department of Pediatrics, Nemour's Children's Hospital, Orlando, Florida;
¹⁹ Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, Texas;Department of Pediatrics, Children's Medical Center, Dallas, Texas;
²⁰ Department of Pediatric and Adolescent Medicine, Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; and.
²¹ Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

PMID: 24935993
PMCID: PMC4531278
DOI: 10.1542/peds.2013-4103

Effectiveness of anti-TNFα for Crohn disease: research in a pediatric learning health system

Christopher B Forrest et al. Pediatrics. 2014 Jul.

. 2014 Jul;134(1):37-44.

doi: 10.1542/peds.2013-4103. Epub 2014 Jun 16.

Authors

Affiliations

¹ Department of Pediatrics, andLeonard Davis Institute of Health Economics, and forrestc@email.chop.edu.
² Department of Pediatrics, The Ohio State University College of Medicine, Nationwide Children's Hospital, Columbus, Ohio;
³ Department of Pediatrics, andCenter for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
⁴ Department of Pediatrics, and.
⁵ Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
⁶ Department of Pediatrics, The University of Vermont College of Medicine, Burlington, Vermont;
⁷ Department of Pediatrics and Communicable Diseases, Division of Pediatric Gastroenterology, University of Michigan, Ann Arbor, Michigan;
⁸ Department of Pediatrics, University of Nevada School of Medicine, Pediatric Gastroenterology and Nutrition Associates, Las Vegas, Nevada;
⁹ Advocate Children's Hospital, UIC College of Medicine, Loyola University School of Medicine, Chicago, Illinois;
¹⁰ Department of Pediatrics, Division of Pediatric Gastroenterology Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware;
¹¹ Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;
¹² Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado;
¹³ Department of Pediatrics, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts;
¹⁴ Department of Medicine, Boston Children's Hospital, Boston, Massachusetts;
¹⁵ Department of Pediatrics, James M. Anderson Center for Health Systems Excellence, and.
¹⁶ Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio;
¹⁷ Department of Pediatrics, Arnold Palmer Hospital for Children, Florida State University, Orlando, Florida;
¹⁸ Department of Pediatrics, Nemour's Children's Hospital, Orlando, Florida;
¹⁹ Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, Texas;Department of Pediatrics, Children's Medical Center, Dallas, Texas;
²⁰ Department of Pediatric and Adolescent Medicine, Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; and.
²¹ Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

PMID: 24935993
PMCID: PMC4531278
DOI: 10.1542/peds.2013-4103

Abstract

Objectives: ImproveCareNow (ICN) is the largest pediatric learning health system in the nation and started as a quality improvement collaborative. To test the feasibility and validity of using ICN data for clinical research, we evaluated the effectiveness of anti-tumor necrosis factor-α (anti-TNFα) agents in the management of pediatric Crohn disease (CD).

Methods: Data were collected in 35 pediatric gastroenterology practices (April 2007 to March 2012) and analyzed as a sequence of nonrandomized trials. Patients who had moderate to severe CD were classified as initiators or non-initiators of anti-TNFα therapy. Among 4130 patients who had pediatric CD, 603 were new users and 1211 were receiving anti-TNFα therapy on entry into ICN.

Results: During a 26-week follow-up period, rate ratios obtained from Cox proportional hazards models, adjusting for patient and disease characteristics and concurrent medications, were 1.53 (95% confidence interval [CI], 1.20-1.96) for clinical remission and 1.74 (95% CI, 1.33-2.29) for corticosteroid-free remission. The rate ratio for corticosteroid-free remission was comparable to the estimate produced by the adult SONIC study, which was a randomized controlled trial on the efficacy of anti-TNFα therapy. The number needed to treat was 5.2 (95% CI, 3.4-11.1) for clinical remission and 5.0 (95% CI, 3.4-10.0) for corticosteroid-free remission.

Conclusions: In routine pediatric gastroenterology practice settings, anti-TNFα therapy was effective at achieving clinical and corticosteroid-free remission for patients who had Crohn disease. Using data from the ICN learning health system for the purpose of observational research is feasible and produces valuable new knowledge.

Keywords: Crohn disease; anti-tumor necrosis factor-α; child; comparative effectiveness research.

PubMed Disclaimer

Figures

**FIGURE 1**
Cumulative probability of remission and corticosteroid-free remission for initiator and non-initiator trials during a 26-week follow-up period.

See this image and copyright information in PMC

Comment in

Demonstrating the learning health system through practical use cases.
Abernethy AP. Abernethy AP. Pediatrics. 2014 Jul;134(1):171-2. doi: 10.1542/peds.2014-1182. Epub 2014 Jun 16. Pediatrics. 2014. PMID: 24935998 No abstract available.

Cited by

Using multiple imputation of real-world data to estimate clinical remission in pediatric inflammatory bowel disease.
Zhang N, Liu C, Steiner SJ, Colletti RB, Baldassano R, Chen S, Cohen S, Kappelman MD, Saeed S, Conklin LS, Strauss R, Volger S, King E, Lo KH. Zhang N, et al. J Comp Eff Res. 2023 Apr;12(4):e220136. doi: 10.57264/cer-2022-0136. Epub 2023 Feb 17. J Comp Eff Res. 2023. PMID: 36799351 Free PMC article.
Clinical Outcome Assessments in Pediatric Patients With Ulcerative Colitis and Crohn's Disease Receiving Biologics: A Retrospective Cohort Study.
Hunter T, Komocsar WJ, Liu C, Colletti RB, Steiner SJ, Dotson JL, Benkov K, Zhang N, Crandall W. Hunter T, et al. Crohns Colitis 360. 2022 Mar 18;4(2):otac009. doi: 10.1093/crocol/otac009. eCollection 2022 Apr. Crohns Colitis 360. 2022. PMID: 36777044 Free PMC article.
The SHOnet learning health system: Infrastructure for continuous learning in pediatric rehabilitation.
Koscielniak N, Jenkins D, Hassani S, Buckon C, Tucker JS, Sienko S, Tucker CA. Koscielniak N, et al. Learn Health Syst. 2022 Feb 15;6(3):e10305. doi: 10.1002/lrh2.10305. eCollection 2022 Jul. Learn Health Syst. 2022. PMID: 35860324 Free PMC article.
Clinical data for paediatric research: the Swiss approach : Proceedings of the National Symposium in Bern, Switzerland, Dec 5-6, 2019.
Rakic M, Jaboyedoff M, Bachmann S, Berger C, Diezi M, do Canto P, Forrest CB, Frey U, Fuchs O, Gervaix A, Gluecksberg AS, Grotzer M, Heininger U, Kahlert CR, Kaiser D, Kopp MV, Lauener R, Neuhaus TJ, Paioni P, Posfay-Barbe K, Ramelli GP, Simeoni U, Simonetti G, Sokollik C, Spycher BD, Kuehni CE. Rakic M, et al. BMC Proc. 2021 Sep 20;15(Suppl 13):19. doi: 10.1186/s12919-021-00226-3. BMC Proc. 2021. PMID: 34538238 Free PMC article.
Measuring engagement in a collaborative learning health system: The case of ImproveCareNow.
Hartley DM, Keck C, Havens M, Margolis PA, Seid M. Hartley DM, et al. Learn Health Syst. 2020 Apr 6;5(2):e10225. doi: 10.1002/lrh2.10225. eCollection 2021 Apr. Learn Health Syst. 2020. PMID: 33889734 Free PMC article.

See all "Cited by" articles

References

1. Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology. 2000;119(4):895–902 - PubMed
1. McDonald JW, Tsoulis DJ, Macdonald JK, Feagan BG. Methotrexate for induction of remission in refractory Crohn’s disease. Cochrane Database Syst Rev. 2012;12:CD003459. - PubMed
1. Turner D, Grossman AB, Rosh J, et al. Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn’s disease. Am J Gastroenterol. 2007;102(12):2804–2812; quiz 2803, 2813 - PubMed
1. Hyams J, Crandall W, Kugathasan S, et al. REACH Study Group . Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132(3):863–873, quiz 1165–1166 - PubMed
1. Peyrin-Biroulet L. Anti-TNF therapy in inflammatory bowel diseases: a huge review. Minerva Gastroenterol Dietol. 2010;56(2):233–243 - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Supplementary concepts

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

[1] Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology. 2000;119(4):895–902 - PubMed

[2] Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology. 2000;119(4):895–902 - PubMed

[3] McDonald JW, Tsoulis DJ, Macdonald JK, Feagan BG. Methotrexate for induction of remission in refractory Crohn’s disease. Cochrane Database Syst Rev. 2012;12:CD003459. - PubMed

[4] McDonald JW, Tsoulis DJ, Macdonald JK, Feagan BG. Methotrexate for induction of remission in refractory Crohn’s disease. Cochrane Database Syst Rev. 2012;12:CD003459. - PubMed

[5] Turner D, Grossman AB, Rosh J, et al. Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn’s disease. Am J Gastroenterol. 2007;102(12):2804–2812; quiz 2803, 2813 - PubMed

[6] Turner D, Grossman AB, Rosh J, et al. Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn’s disease. Am J Gastroenterol. 2007;102(12):2804–2812; quiz 2803, 2813 - PubMed

[7] Hyams J, Crandall W, Kugathasan S, et al. REACH Study Group . Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132(3):863–873, quiz 1165–1166 - PubMed

[8] Hyams J, Crandall W, Kugathasan S, et al. REACH Study Group . Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132(3):863–873, quiz 1165–1166 - PubMed

[9] Peyrin-Biroulet L. Anti-TNF therapy in inflammatory bowel diseases: a huge review. Minerva Gastroenterol Dietol. 2010;56(2):233–243 - PubMed

[10] Peyrin-Biroulet L. Anti-TNF therapy in inflammatory bowel diseases: a huge review. Minerva Gastroenterol Dietol. 2010;56(2):233–243 - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Effectiveness of anti-TNFα for Crohn disease: research in a pediatric learning health system

Affiliations

Effectiveness of anti-TNFα for Crohn disease: research in a pediatric learning health system

Authors

Affiliations

Abstract

Figures

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous

Abstract

Figures

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Supplementary concepts

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous