Methotrexate Following Unsuccessful Thiopurine Therapy in Pediatric Crohn's Disease

Turner, Dan; Grossman, Andrew B.; Rosh, Joel R.; Kugathasan, Subra; Gilman, Ashley; Baldassano, Robert N.; Griffiths, Anne M.

doi:10.1111/j.1572-0241.2007.01474.x

Cited by 103 publications

(102 citation statements)

References 36 publications

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“…Over thelastseveraldecades,therapeutic advances in the treatment of pediatric Crohn disease (CD) have included the widespread use of immunomodulators such as 6-mercaptopurine, azathioprine, and methotrexate. [1][2][3] More recently, the anti-tumor necrosis factor a (anti-TNFa) biological agents (eg, infliximab and adalimumab) have been adopted as a treatment of moderate to severe pediatric CD. 4 Although several studies on adult patients who have CD have shown a comparative benefit of anti-TNFa versus placebo 5 and thiopurines, 6 these same studies have not been done in children because of practical (time and cost) and ethical (withholding an efficacious treatment) challenges.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Anti-TNFα for Crohn Disease: Research in a Pediatric Learning Health System

et al. 2014

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WHAT'S KNOWN ON THIS SUBJECT: Studies on adult patients who have Crohn disease have shown a comparative benefit of antiTNFa versus placebo and thiopurines. These same studies have not been done in children, because of time, cost, and ethical (withholding an efficacious treatment) challenges. WHAT THIS STUDY ADDS:Anti-TNFa therapy administered in routine practice to children with Crohn disease was more effective than usual care at achieving clinical and corticosteroid-free remission. Using data from the ImproveCareNow learning health system for observational research is feasible and produces valuable evidence. 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-a (anti-TNFa) 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-TNFa therapy. Among 4130 patients who had pediatric CD, 603 were new users and 1211 were receiving anti-TNFa 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-TNFa 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-TNFa therapy was effective at achieving clinical and corticosteroidfree 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. Over thelastseveraldecades,therapeutic advances in the treatment of pediatric Crohn disease (CD) have included the widespread use of immunomodulators such as 6-mercaptopurine, azathioprine, and methotrexate. [1][2][3] More recently, the anti-tumor necrosis factor a (anti-TNFa) biological agents (eg, infliximab and adalimumab) have been adopted as a treatment of moderate to severe pediatric CD. 4 Although several studies on adult patients who have CD have shown a comparative benefit of anti-TNFa versus placebo 5 and thiopurines, 6 these same studies have not been done in children because of practical (time and cost) and ethical (withholding an efficacious treatment) challenges.The cost of anti-TNFa is in the range...

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Section: Discussionmentioning

confidence: 99%

Effectiveness of Anti-TNFα for Crohn Disease: Research in a Pediatric Learning Health System

et al. 2014

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“…4 It has remained a topic of great debate whether childhood-onset disease is etiologically distinct from adultonset disease-a debate recently catalyzed by the search for susceptibility genes in CD and UC. Clinical experience, including the early requirement for second-line immunomodulatory drugs 5,6 in childhood-onset disease, suggests that childhood-onset disease may have a more "severe" phenotype. This hypothesis has been supported to some extent by the limited available data suggesting that childhood-onset CD may be characterized by extensive intestinal involvement at presentation.…”

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confidence: 99%

Definition of Phenotypic Characteristics of Childhood-Onset Inflammatory Bowel Disease

et al. 2008

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See Dubinsky MC et al on page 1105 in CGH;See editorial on page 1038. Background & Aims:Childhood-onset inflammatory bowel disease (IBD) might be etiologically different from adult-onset IBD. We analyzed disease phenotypes and progression of childhood-onset disease and compared them with characteristics of adult-onset disease in patients in Scotland. ; 43% vs 3%; P < .0001; OR, 23.36; 95% CI, 13.45-40.59) with less isolated ileal (L1; 2% vs 31%; P < .0001; OR, 0.06; 95% CI, 0.03-0.12) or colonic disease (L2; 15% vs 36%; P < .0001; OR, 0.31; 95% CI, 0.21-0.46). UC was extensive in 82% of the children at diagnosis, versus 48% of adults (P < .0001; OR, 5.08; 95% CI, 2.73-9.45); 46% of the children progressed to develop extensive colitis during followup. Forty-six percent of children with CD and 35% with UC required immunomodulatory therapy within 12 months of diagnosis. The median time to first surgery was longer in childhood-onset than adult-onset patients with CD (13.7 vs 7.8 years; P < .001); the reverse was true

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“…42 . As yet, there is no mechanism proposed at to potential pathways which may explain this improvement in growth for either AZA or MTX.…”

Section: Discussionmentioning

confidence: 99%

Disease Status and Pubertal Stage Predict Improved Growth in Antitumor Necrosis Factor Therapy for Pediatric Inflammatory Bowel Disease

Cameron

Altowati

Rogers

et al. 2017

J. pediatr. gastroenterol. nutr.

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Methotrexate Following Unsuccessful Thiopurine Therapy in Pediatric Crohn's Disease

Abstract: Methotrexate appears effective in maintaining remission in pediatric Crohn's disease, when thiopurines have failed. Consideration should be given to its use earlier in pediatric treatment algorithms.

Cited by 103 publications

References 36 publications

Effectiveness of Anti-TNFα for Crohn Disease: Research in a Pediatric Learning Health System

Effectiveness of Anti-TNFα for Crohn Disease: Research in a Pediatric Learning Health System

Definition of Phenotypic Characteristics of Childhood-Onset Inflammatory Bowel Disease

Disease Status and Pubertal Stage Predict Improved Growth in Antitumor Necrosis Factor Therapy for Pediatric Inflammatory Bowel Disease

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