Severe Pediatric Ulcerative Colitis: A Prospective Multicenter Study of Outcomes and Predictors of Response

Dan Turner; David Mack; Neal Leleiko; Thomas D. Walters; Krista Uusoue; Steven T. Leach; Andrew S. Day; Wallace Crandall; Mark S. Silverberg; James Markowitz; Anthony R. Otley; David Keljo; Petar Mamula; Subra Kugathasan; Jeffrey Hyams; Anne M. Griffiths

doi:10.1053/j.gastro.2010.02.047

Severe Pediatric Ulcerative Colitis: A Prospective Multicenter Study of Outcomes and Predictors of Response

Dan Turner, David Mack, Neal Leleiko, Thomas D. Walters, Krista Uusoue, Steven T. Leach, Andrew S. Day, Wallace Crandall, Mark S. Silverberg, James Markowitz, Anthony R. Otley, David Keljo, Petar Mamula, Subra Kugathasan, Jeffrey Hyams, Anne M. Griffiths^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

234 Scopus citations

Abstract

Background & Aims: In a prospective study of children with severe ulcerative colitis (UC), we aimed to assess outcomes and to identify predictors of nonresponse to intravenous corticosteroids. Methods: A total of 128 children (47% males; 12.9 ± 3.9 y) hospitalized for severe UC were enrolled from 10 pediatric centers. Clinical and laboratory data and the Pediatric UC Activity Index (PUCAI) were recorded throughout the admission. Patients were followed up for 1 year postdischarge. Results: Thirty-seven (29%; 95% confidence interval [CI], 22%-37%) children failed intravenous corticosteroids and received, within 10.5 ± 6.4 days, cyclosporine (n = 1; 3%), colectomy (n = 3; 8%), or infliximab (n = 33; 89%). Several predictors were associated with intravenous corticosteroids failure, but the best model included number of stools, amount of blood, age, and new-onset disease (odds ratio [OR], 1.9; 95% CI, 1.1-3.5; OR, 2.5; 95% CI, 1.3-4.6; OR, 1.2; 95% CI, 1.04-1.36; and OR, 0.27; 95% CI, 0.1-0.7, respectively). The PUCAI, followed closely by the Travis rule, strongly predicted response when compared with other measures (Seo and Lindgren indices, C-reactive protein level, and fecal calprotectin level) (P < .001). Aiming for sensitivity on day 3, a PUCAI greater than 45 screened for patients likely to fail intravenous corticosteroids (negative predictive value, 94%; positive predictive value, 43%; P < .001). Aiming for specificity on day 5, a PUCAI score greater than 70 optimally guided implementation of salvage therapy (positive predictive value, 100%; negative predictive value, 79%; P < .001). Twenty-five of 33 children treated with infliximab responded. The overall cumulative colectomy rate was 9% and 19% by discharge and 1-year, respectively. The day 3 PUCAI score predicted response up to 1 year postdischarge (P < .001; time to salvage therapy). Conclusions: The PUCAI, calculated on days 3 and 5 of steroid therapy, can identify patients requiring salvage therapy. Infliximab is an effective therapy in steroid-refractory pediatric UC.

Original language	English
Pages (from-to)	2282-2291
Number of pages	10
Journal	Gastroenterology
Volume	138
Issue number	7
DOIs	https://doi.org/10.1053/j.gastro.2010.02.047
State	Published - Jun 2010
Externally published	Yes

Bibliographical note

Funding Information:
The authors disclose the following: this investigator-initiated study was partially funded from Schering-Plough Canada, Inc. Schering was not involved in any part of the study design, protocol preparation, study conduct, data processing, analysis, and manuscript writing. Study participants were aware of this potential conflict of interest.

Funding Information:
Funding Supported by Schering-Plough Canada, Inc.

Keywords

Infliximab
PUCAI
Pediatrics
Severe Ulcerative Colitis

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10.1053/j.gastro.2010.02.047

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Turner, D., Mack, D., Leleiko, N., Walters, T. D., Uusoue, K., Leach, S. T., Day, A. S., Crandall, W., Silverberg, M. S., Markowitz, J., Otley, A. R., Keljo, D., Mamula, P., Kugathasan, S., Hyams, J., & Griffiths, A. M. (2010). Severe Pediatric Ulcerative Colitis: A Prospective Multicenter Study of Outcomes and Predictors of Response. Gastroenterology, 138(7), 2282-2291. https://doi.org/10.1053/j.gastro.2010.02.047

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title = "Severe Pediatric Ulcerative Colitis: A Prospective Multicenter Study of Outcomes and Predictors of Response",

abstract = "Background & Aims: In a prospective study of children with severe ulcerative colitis (UC), we aimed to assess outcomes and to identify predictors of nonresponse to intravenous corticosteroids. Methods: A total of 128 children (47% males; 12.9 ± 3.9 y) hospitalized for severe UC were enrolled from 10 pediatric centers. Clinical and laboratory data and the Pediatric UC Activity Index (PUCAI) were recorded throughout the admission. Patients were followed up for 1 year postdischarge. Results: Thirty-seven (29%; 95% confidence interval [CI], 22%-37%) children failed intravenous corticosteroids and received, within 10.5 ± 6.4 days, cyclosporine (n = 1; 3%), colectomy (n = 3; 8%), or infliximab (n = 33; 89%). Several predictors were associated with intravenous corticosteroids failure, but the best model included number of stools, amount of blood, age, and new-onset disease (odds ratio [OR], 1.9; 95% CI, 1.1-3.5; OR, 2.5; 95% CI, 1.3-4.6; OR, 1.2; 95% CI, 1.04-1.36; and OR, 0.27; 95% CI, 0.1-0.7, respectively). The PUCAI, followed closely by the Travis rule, strongly predicted response when compared with other measures (Seo and Lindgren indices, C-reactive protein level, and fecal calprotectin level) (P < .001). Aiming for sensitivity on day 3, a PUCAI greater than 45 screened for patients likely to fail intravenous corticosteroids (negative predictive value, 94%; positive predictive value, 43%; P < .001). Aiming for specificity on day 5, a PUCAI score greater than 70 optimally guided implementation of salvage therapy (positive predictive value, 100%; negative predictive value, 79%; P < .001). Twenty-five of 33 children treated with infliximab responded. The overall cumulative colectomy rate was 9% and 19% by discharge and 1-year, respectively. The day 3 PUCAI score predicted response up to 1 year postdischarge (P < .001; time to salvage therapy). Conclusions: The PUCAI, calculated on days 3 and 5 of steroid therapy, can identify patients requiring salvage therapy. Infliximab is an effective therapy in steroid-refractory pediatric UC.",

keywords = "Infliximab, PUCAI, Pediatrics, Severe Ulcerative Colitis",

author = "Dan Turner and David Mack and Neal Leleiko and Walters, {Thomas D.} and Krista Uusoue and Leach, {Steven T.} and Day, {Andrew S.} and Wallace Crandall and Silverberg, {Mark S.} and James Markowitz and Otley, {Anthony R.} and David Keljo and Petar Mamula and Subra Kugathasan and Jeffrey Hyams and Griffiths, {Anne M.}",

note = "Funding Information: The authors disclose the following: this investigator-initiated study was partially funded from Schering-Plough Canada, Inc. Schering was not involved in any part of the study design, protocol preparation, study conduct, data processing, analysis, and manuscript writing. Study participants were aware of this potential conflict of interest. Funding Information: Funding Supported by Schering-Plough Canada, Inc. ",

year = "2010",

month = jun,

doi = "10.1053/j.gastro.2010.02.047",

language = "אנגלית",

volume = "138",

pages = "2282--2291",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders",

number = "7",

}

Turner, D, Mack, D, Leleiko, N, Walters, TD, Uusoue, K, Leach, ST, Day, AS, Crandall, W, Silverberg, MS, Markowitz, J, Otley, AR, Keljo, D, Mamula, P, Kugathasan, S, Hyams, J & Griffiths, AM 2010, 'Severe Pediatric Ulcerative Colitis: A Prospective Multicenter Study of Outcomes and Predictors of Response', Gastroenterology, vol. 138, no. 7, pp. 2282-2291. https://doi.org/10.1053/j.gastro.2010.02.047

TY - JOUR

T1 - Severe Pediatric Ulcerative Colitis

T2 - A Prospective Multicenter Study of Outcomes and Predictors of Response

AU - Turner, Dan

AU - Mack, David

AU - Leleiko, Neal

AU - Walters, Thomas D.

AU - Uusoue, Krista

AU - Leach, Steven T.

AU - Day, Andrew S.

AU - Crandall, Wallace

AU - Silverberg, Mark S.

AU - Markowitz, James

AU - Otley, Anthony R.

AU - Keljo, David

AU - Mamula, Petar

AU - Kugathasan, Subra

AU - Hyams, Jeffrey

AU - Griffiths, Anne M.

N1 - Funding Information: The authors disclose the following: this investigator-initiated study was partially funded from Schering-Plough Canada, Inc. Schering was not involved in any part of the study design, protocol preparation, study conduct, data processing, analysis, and manuscript writing. Study participants were aware of this potential conflict of interest. Funding Information: Funding Supported by Schering-Plough Canada, Inc.

PY - 2010/6

Y1 - 2010/6

N2 - Background & Aims: In a prospective study of children with severe ulcerative colitis (UC), we aimed to assess outcomes and to identify predictors of nonresponse to intravenous corticosteroids. Methods: A total of 128 children (47% males; 12.9 ± 3.9 y) hospitalized for severe UC were enrolled from 10 pediatric centers. Clinical and laboratory data and the Pediatric UC Activity Index (PUCAI) were recorded throughout the admission. Patients were followed up for 1 year postdischarge. Results: Thirty-seven (29%; 95% confidence interval [CI], 22%-37%) children failed intravenous corticosteroids and received, within 10.5 ± 6.4 days, cyclosporine (n = 1; 3%), colectomy (n = 3; 8%), or infliximab (n = 33; 89%). Several predictors were associated with intravenous corticosteroids failure, but the best model included number of stools, amount of blood, age, and new-onset disease (odds ratio [OR], 1.9; 95% CI, 1.1-3.5; OR, 2.5; 95% CI, 1.3-4.6; OR, 1.2; 95% CI, 1.04-1.36; and OR, 0.27; 95% CI, 0.1-0.7, respectively). The PUCAI, followed closely by the Travis rule, strongly predicted response when compared with other measures (Seo and Lindgren indices, C-reactive protein level, and fecal calprotectin level) (P < .001). Aiming for sensitivity on day 3, a PUCAI greater than 45 screened for patients likely to fail intravenous corticosteroids (negative predictive value, 94%; positive predictive value, 43%; P < .001). Aiming for specificity on day 5, a PUCAI score greater than 70 optimally guided implementation of salvage therapy (positive predictive value, 100%; negative predictive value, 79%; P < .001). Twenty-five of 33 children treated with infliximab responded. The overall cumulative colectomy rate was 9% and 19% by discharge and 1-year, respectively. The day 3 PUCAI score predicted response up to 1 year postdischarge (P < .001; time to salvage therapy). Conclusions: The PUCAI, calculated on days 3 and 5 of steroid therapy, can identify patients requiring salvage therapy. Infliximab is an effective therapy in steroid-refractory pediatric UC.

AB - Background & Aims: In a prospective study of children with severe ulcerative colitis (UC), we aimed to assess outcomes and to identify predictors of nonresponse to intravenous corticosteroids. Methods: A total of 128 children (47% males; 12.9 ± 3.9 y) hospitalized for severe UC were enrolled from 10 pediatric centers. Clinical and laboratory data and the Pediatric UC Activity Index (PUCAI) were recorded throughout the admission. Patients were followed up for 1 year postdischarge. Results: Thirty-seven (29%; 95% confidence interval [CI], 22%-37%) children failed intravenous corticosteroids and received, within 10.5 ± 6.4 days, cyclosporine (n = 1; 3%), colectomy (n = 3; 8%), or infliximab (n = 33; 89%). Several predictors were associated with intravenous corticosteroids failure, but the best model included number of stools, amount of blood, age, and new-onset disease (odds ratio [OR], 1.9; 95% CI, 1.1-3.5; OR, 2.5; 95% CI, 1.3-4.6; OR, 1.2; 95% CI, 1.04-1.36; and OR, 0.27; 95% CI, 0.1-0.7, respectively). The PUCAI, followed closely by the Travis rule, strongly predicted response when compared with other measures (Seo and Lindgren indices, C-reactive protein level, and fecal calprotectin level) (P < .001). Aiming for sensitivity on day 3, a PUCAI greater than 45 screened for patients likely to fail intravenous corticosteroids (negative predictive value, 94%; positive predictive value, 43%; P < .001). Aiming for specificity on day 5, a PUCAI score greater than 70 optimally guided implementation of salvage therapy (positive predictive value, 100%; negative predictive value, 79%; P < .001). Twenty-five of 33 children treated with infliximab responded. The overall cumulative colectomy rate was 9% and 19% by discharge and 1-year, respectively. The day 3 PUCAI score predicted response up to 1 year postdischarge (P < .001; time to salvage therapy). Conclusions: The PUCAI, calculated on days 3 and 5 of steroid therapy, can identify patients requiring salvage therapy. Infliximab is an effective therapy in steroid-refractory pediatric UC.

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Severe Pediatric Ulcerative Colitis: A Prospective Multicenter Study of Outcomes and Predictors of Response

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