Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study

Jeffrey S. Hyams, Sonia Davis, David R. Mack, Brendan Boyle, Anne M. Griffiths, Neal S. LeLeiko, Cary G. Sauer, David J. Keljo, James Markowitz, Susan S. Baker, Joel Rosh, Robert N. Baldassano, Ashish Patel, Marian Pfefferkorn, Anthony Otley, Melvin Heyman, Joshua Noe, Maria Oliva-Hemker, Paul Rufo, Jennifer StropleDavid Ziring, Stephen L. Guthery, Boris Sudel, Keith Benkov, Prateek Wali, Dedrick Moulton, Jonathan Evans, Michael D. Kappelman, Alison Marquis, Francisco A. Sylvester, Margaret H. Collins, Suresh Venkateswaran, Marla Dubinsky, Vin Tangpricha, Krista L. Spada, Ashley Britt, Bradley Saul, Nathan Gotman, Jessie Wang, Jose Serrano, Subra Kugathasan, Thomas Walters, Lee A. Denson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background Previous retrospective studies of paediatric ulcerative colitis have had limited ability to describe disease progression and identify predictors of treatment response. In this study, we aimed to identify characteristics associated with outcomes following standardised therapy after initial diagnosis. Methods The PROTECT multicentre inception cohort study was based at 29 centres in the USA and Canada and included paediatric patients aged 4–17 years who were newly diagnosed with ulcerative colitis. Guided by the Pediatric Ulcerative Colitis Activity Index (PUCAI), patients received initial standardised treatment with mesalazine (PUCAI 10–30) oral corticosteroids (PUCAI 35–60), or intravenous corticosteroids (PUCAI ≥65). The key outcomes for this analysis were week 12 corticosteroid-free remission, defined as PUCAI less than 10 and taking only mesalazine, and treatment escalation during the 12 study weeks to anti-tumour necrosis factor α (TNFα) agents, immunomodulators, or colectomy among those initially treated with intravenous corticosteroids. We identified independent predictors of outcome through multivariable logistic regression using a per-protocol approach. This study is registered with ClinicalTrials.gov, number NCT01536535. Findings Patients were recruited between July 10, 2012, and April 21, 2015. 428 children initiated mesalazine (n=136), oral corticosteroids (n=144), or intravenous corticosteroids (n=148). Initial mean PUCAI was 31·1 (SD 13·3) in children initiating with mesalazine, 50·4 (13·8) in those initiating oral corticosteroids, and 66·9 (13·7) in those initiating intravenous corticosteroids (p<0·0001 for between-group comparison). Week 12 outcome data were available for 132 patients who initiated with mesalazine, 141 with oral corticosteroids, and 143 with intravenous corticosteroids. Corticosteroid-free remission with the patient receiving mesalazine treatment only at 12 weeks was achieved by 64 (48%) patients in the mesalazine group, 47 (33%) in the oral corticosteroid group, and 30 (21%) in the intravenous corticosteroid group (p<0·0001). Treatment escalation was required by nine (7%) patients in the mesalazine group, 21 (15%) in the oral corticosteroid group, and 52 (36%) in the intravenous corticosteroid group (p<0·0001). Eight patients, all of whom were initially treated with intravenous corticosteroids, underwent colectomy. Predictors of week 12 corticosteroid-free remission were baseline PUCAI less than 35 (odds ratio 2·44, 95% CI 1·41–4·22; p=0·0015), higher baseline albumin by 1 g/dL increments among children younger than 12 years (4·05, 1·90–8·64; p=0·00030), and week 4 remission (6·26, 3·79–10·35; p<0·0001). Predictors of treatment escalation by week 12 in patients initially treated with intravenous corticosteroids included baseline total Mayo score of 11 or higher (2·59, 0·93–7·21; p=0·068 [retained in model due to clinical relevance]), rectal biopsy eosinophil count less than or equal to 32 cells per high power field (4·55, 1·62–12·78; p=0·0040), rectal biopsy surface villiform changes (3·05, 1·09–8·56; p=0·034), and not achieving week 4 remission (30·28, 6·36–144·20; p<0·0001). Interpretation Our findings provide guidelines to assess the response of children newly diagnosed with ulcerative colitis to standardised initial therapy and identify predictors of treatment response and failure. These data suggest that additional therapeutic interventions might be warranted to improve early outcomes, especially in patients presenting with severe disease and requiring intravenous corticosteroids. Funding National Institutes of Health.

Original languageEnglish (US)
Pages (from-to)855-868
Number of pages14
JournalThe Lancet Gastroenterology and Hepatology
Volume2
Issue number12
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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Ulcerative Colitis
Adrenal Cortex Hormones
Cohort Studies
Mesalamine
Therapeutics
Colectomy
Biopsy
Pediatric ulcerative colitis
National Institutes of Health (U.S.)
Immunologic Factors
Treatment Failure
Eosinophils

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Hyams, Jeffrey S. ; Davis, Sonia ; Mack, David R. ; Boyle, Brendan ; Griffiths, Anne M. ; LeLeiko, Neal S. ; Sauer, Cary G. ; Keljo, David J. ; Markowitz, James ; Baker, Susan S. ; Rosh, Joel ; Baldassano, Robert N. ; Patel, Ashish ; Pfefferkorn, Marian ; Otley, Anthony ; Heyman, Melvin ; Noe, Joshua ; Oliva-Hemker, Maria ; Rufo, Paul ; Strople, Jennifer ; Ziring, David ; Guthery, Stephen L. ; Sudel, Boris ; Benkov, Keith ; Wali, Prateek ; Moulton, Dedrick ; Evans, Jonathan ; Kappelman, Michael D. ; Marquis, Alison ; Sylvester, Francisco A. ; Collins, Margaret H. ; Venkateswaran, Suresh ; Dubinsky, Marla ; Tangpricha, Vin ; Spada, Krista L. ; Britt, Ashley ; Saul, Bradley ; Gotman, Nathan ; Wang, Jessie ; Serrano, Jose ; Kugathasan, Subra ; Walters, Thomas ; Denson, Lee A. / Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT) : a multicentre inception cohort study. In: The Lancet Gastroenterology and Hepatology. 2017 ; Vol. 2, No. 12. pp. 855-868.
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abstract = "Background Previous retrospective studies of paediatric ulcerative colitis have had limited ability to describe disease progression and identify predictors of treatment response. In this study, we aimed to identify characteristics associated with outcomes following standardised therapy after initial diagnosis. Methods The PROTECT multicentre inception cohort study was based at 29 centres in the USA and Canada and included paediatric patients aged 4–17 years who were newly diagnosed with ulcerative colitis. Guided by the Pediatric Ulcerative Colitis Activity Index (PUCAI), patients received initial standardised treatment with mesalazine (PUCAI 10–30) oral corticosteroids (PUCAI 35–60), or intravenous corticosteroids (PUCAI ≥65). The key outcomes for this analysis were week 12 corticosteroid-free remission, defined as PUCAI less than 10 and taking only mesalazine, and treatment escalation during the 12 study weeks to anti-tumour necrosis factor α (TNFα) agents, immunomodulators, or colectomy among those initially treated with intravenous corticosteroids. We identified independent predictors of outcome through multivariable logistic regression using a per-protocol approach. This study is registered with ClinicalTrials.gov, number NCT01536535. Findings Patients were recruited between July 10, 2012, and April 21, 2015. 428 children initiated mesalazine (n=136), oral corticosteroids (n=144), or intravenous corticosteroids (n=148). Initial mean PUCAI was 31·1 (SD 13·3) in children initiating with mesalazine, 50·4 (13·8) in those initiating oral corticosteroids, and 66·9 (13·7) in those initiating intravenous corticosteroids (p<0·0001 for between-group comparison). Week 12 outcome data were available for 132 patients who initiated with mesalazine, 141 with oral corticosteroids, and 143 with intravenous corticosteroids. Corticosteroid-free remission with the patient receiving mesalazine treatment only at 12 weeks was achieved by 64 (48{\%}) patients in the mesalazine group, 47 (33{\%}) in the oral corticosteroid group, and 30 (21{\%}) in the intravenous corticosteroid group (p<0·0001). Treatment escalation was required by nine (7{\%}) patients in the mesalazine group, 21 (15{\%}) in the oral corticosteroid group, and 52 (36{\%}) in the intravenous corticosteroid group (p<0·0001). Eight patients, all of whom were initially treated with intravenous corticosteroids, underwent colectomy. Predictors of week 12 corticosteroid-free remission were baseline PUCAI less than 35 (odds ratio 2·44, 95{\%} CI 1·41–4·22; p=0·0015), higher baseline albumin by 1 g/dL increments among children younger than 12 years (4·05, 1·90–8·64; p=0·00030), and week 4 remission (6·26, 3·79–10·35; p<0·0001). Predictors of treatment escalation by week 12 in patients initially treated with intravenous corticosteroids included baseline total Mayo score of 11 or higher (2·59, 0·93–7·21; p=0·068 [retained in model due to clinical relevance]), rectal biopsy eosinophil count less than or equal to 32 cells per high power field (4·55, 1·62–12·78; p=0·0040), rectal biopsy surface villiform changes (3·05, 1·09–8·56; p=0·034), and not achieving week 4 remission (30·28, 6·36–144·20; p<0·0001). Interpretation Our findings provide guidelines to assess the response of children newly diagnosed with ulcerative colitis to standardised initial therapy and identify predictors of treatment response and failure. These data suggest that additional therapeutic interventions might be warranted to improve early outcomes, especially in patients presenting with severe disease and requiring intravenous corticosteroids. Funding National Institutes of Health.",
author = "Hyams, {Jeffrey S.} and Sonia Davis and Mack, {David R.} and Brendan Boyle and Griffiths, {Anne M.} and LeLeiko, {Neal S.} and Sauer, {Cary G.} and Keljo, {David J.} and James Markowitz and Baker, {Susan S.} and Joel Rosh and Baldassano, {Robert N.} and Ashish Patel and Marian Pfefferkorn and Anthony Otley and Melvin Heyman and Joshua Noe and Maria Oliva-Hemker and Paul Rufo and Jennifer Strople and David Ziring and Guthery, {Stephen L.} and Boris Sudel and Keith Benkov and Prateek Wali and Dedrick Moulton and Jonathan Evans and Kappelman, {Michael D.} and Alison Marquis and Sylvester, {Francisco A.} and Collins, {Margaret H.} and Suresh Venkateswaran and Marla Dubinsky and Vin Tangpricha and Spada, {Krista L.} and Ashley Britt and Bradley Saul and Nathan Gotman and Jessie Wang and Jose Serrano and Subra Kugathasan and Thomas Walters and Denson, {Lee A.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1016/S2468-1253(17)30252-2",
language = "English (US)",
volume = "2",
pages = "855--868",
journal = "The Lancet Gastroenterology and Hepatology",
issn = "2468-1253",
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Hyams, JS, Davis, S, Mack, DR, Boyle, B, Griffiths, AM, LeLeiko, NS, Sauer, CG, Keljo, DJ, Markowitz, J, Baker, SS, Rosh, J, Baldassano, RN, Patel, A, Pfefferkorn, M, Otley, A, Heyman, M, Noe, J, Oliva-Hemker, M, Rufo, P, Strople, J, Ziring, D, Guthery, SL, Sudel, B, Benkov, K, Wali, P, Moulton, D, Evans, J, Kappelman, MD, Marquis, A, Sylvester, FA, Collins, MH, Venkateswaran, S, Dubinsky, M, Tangpricha, V, Spada, KL, Britt, A, Saul, B, Gotman, N, Wang, J, Serrano, J, Kugathasan, S, Walters, T & Denson, LA 2017, 'Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study', The Lancet Gastroenterology and Hepatology, vol. 2, no. 12, pp. 855-868. https://doi.org/10.1016/S2468-1253(17)30252-2

Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT) : a multicentre inception cohort study. / Hyams, Jeffrey S.; Davis, Sonia; Mack, David R.; Boyle, Brendan; Griffiths, Anne M.; LeLeiko, Neal S.; Sauer, Cary G.; Keljo, David J.; Markowitz, James; Baker, Susan S.; Rosh, Joel; Baldassano, Robert N.; Patel, Ashish; Pfefferkorn, Marian; Otley, Anthony; Heyman, Melvin; Noe, Joshua; Oliva-Hemker, Maria; Rufo, Paul; Strople, Jennifer; Ziring, David; Guthery, Stephen L.; Sudel, Boris; Benkov, Keith; Wali, Prateek; Moulton, Dedrick; Evans, Jonathan; Kappelman, Michael D.; Marquis, Alison; Sylvester, Francisco A.; Collins, Margaret H.; Venkateswaran, Suresh; Dubinsky, Marla; Tangpricha, Vin; Spada, Krista L.; Britt, Ashley; Saul, Bradley; Gotman, Nathan; Wang, Jessie; Serrano, Jose; Kugathasan, Subra; Walters, Thomas; Denson, Lee A.

In: The Lancet Gastroenterology and Hepatology, Vol. 2, No. 12, 01.12.2017, p. 855-868.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT)

T2 - a multicentre inception cohort study

AU - Hyams, Jeffrey S.

AU - Davis, Sonia

AU - Mack, David R.

AU - Boyle, Brendan

AU - Griffiths, Anne M.

AU - LeLeiko, Neal S.

AU - Sauer, Cary G.

AU - Keljo, David J.

AU - Markowitz, James

AU - Baker, Susan S.

AU - Rosh, Joel

AU - Baldassano, Robert N.

AU - Patel, Ashish

AU - Pfefferkorn, Marian

AU - Otley, Anthony

AU - Heyman, Melvin

AU - Noe, Joshua

AU - Oliva-Hemker, Maria

AU - Rufo, Paul

AU - Strople, Jennifer

AU - Ziring, David

AU - Guthery, Stephen L.

AU - Sudel, Boris

AU - Benkov, Keith

AU - Wali, Prateek

AU - Moulton, Dedrick

AU - Evans, Jonathan

AU - Kappelman, Michael D.

AU - Marquis, Alison

AU - Sylvester, Francisco A.

AU - Collins, Margaret H.

AU - Venkateswaran, Suresh

AU - Dubinsky, Marla

AU - Tangpricha, Vin

AU - Spada, Krista L.

AU - Britt, Ashley

AU - Saul, Bradley

AU - Gotman, Nathan

AU - Wang, Jessie

AU - Serrano, Jose

AU - Kugathasan, Subra

AU - Walters, Thomas

AU - Denson, Lee A.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background Previous retrospective studies of paediatric ulcerative colitis have had limited ability to describe disease progression and identify predictors of treatment response. In this study, we aimed to identify characteristics associated with outcomes following standardised therapy after initial diagnosis. Methods The PROTECT multicentre inception cohort study was based at 29 centres in the USA and Canada and included paediatric patients aged 4–17 years who were newly diagnosed with ulcerative colitis. Guided by the Pediatric Ulcerative Colitis Activity Index (PUCAI), patients received initial standardised treatment with mesalazine (PUCAI 10–30) oral corticosteroids (PUCAI 35–60), or intravenous corticosteroids (PUCAI ≥65). The key outcomes for this analysis were week 12 corticosteroid-free remission, defined as PUCAI less than 10 and taking only mesalazine, and treatment escalation during the 12 study weeks to anti-tumour necrosis factor α (TNFα) agents, immunomodulators, or colectomy among those initially treated with intravenous corticosteroids. We identified independent predictors of outcome through multivariable logistic regression using a per-protocol approach. This study is registered with ClinicalTrials.gov, number NCT01536535. Findings Patients were recruited between July 10, 2012, and April 21, 2015. 428 children initiated mesalazine (n=136), oral corticosteroids (n=144), or intravenous corticosteroids (n=148). Initial mean PUCAI was 31·1 (SD 13·3) in children initiating with mesalazine, 50·4 (13·8) in those initiating oral corticosteroids, and 66·9 (13·7) in those initiating intravenous corticosteroids (p<0·0001 for between-group comparison). Week 12 outcome data were available for 132 patients who initiated with mesalazine, 141 with oral corticosteroids, and 143 with intravenous corticosteroids. Corticosteroid-free remission with the patient receiving mesalazine treatment only at 12 weeks was achieved by 64 (48%) patients in the mesalazine group, 47 (33%) in the oral corticosteroid group, and 30 (21%) in the intravenous corticosteroid group (p<0·0001). Treatment escalation was required by nine (7%) patients in the mesalazine group, 21 (15%) in the oral corticosteroid group, and 52 (36%) in the intravenous corticosteroid group (p<0·0001). Eight patients, all of whom were initially treated with intravenous corticosteroids, underwent colectomy. Predictors of week 12 corticosteroid-free remission were baseline PUCAI less than 35 (odds ratio 2·44, 95% CI 1·41–4·22; p=0·0015), higher baseline albumin by 1 g/dL increments among children younger than 12 years (4·05, 1·90–8·64; p=0·00030), and week 4 remission (6·26, 3·79–10·35; p<0·0001). Predictors of treatment escalation by week 12 in patients initially treated with intravenous corticosteroids included baseline total Mayo score of 11 or higher (2·59, 0·93–7·21; p=0·068 [retained in model due to clinical relevance]), rectal biopsy eosinophil count less than or equal to 32 cells per high power field (4·55, 1·62–12·78; p=0·0040), rectal biopsy surface villiform changes (3·05, 1·09–8·56; p=0·034), and not achieving week 4 remission (30·28, 6·36–144·20; p<0·0001). Interpretation Our findings provide guidelines to assess the response of children newly diagnosed with ulcerative colitis to standardised initial therapy and identify predictors of treatment response and failure. These data suggest that additional therapeutic interventions might be warranted to improve early outcomes, especially in patients presenting with severe disease and requiring intravenous corticosteroids. Funding National Institutes of Health.

AB - Background Previous retrospective studies of paediatric ulcerative colitis have had limited ability to describe disease progression and identify predictors of treatment response. In this study, we aimed to identify characteristics associated with outcomes following standardised therapy after initial diagnosis. Methods The PROTECT multicentre inception cohort study was based at 29 centres in the USA and Canada and included paediatric patients aged 4–17 years who were newly diagnosed with ulcerative colitis. Guided by the Pediatric Ulcerative Colitis Activity Index (PUCAI), patients received initial standardised treatment with mesalazine (PUCAI 10–30) oral corticosteroids (PUCAI 35–60), or intravenous corticosteroids (PUCAI ≥65). The key outcomes for this analysis were week 12 corticosteroid-free remission, defined as PUCAI less than 10 and taking only mesalazine, and treatment escalation during the 12 study weeks to anti-tumour necrosis factor α (TNFα) agents, immunomodulators, or colectomy among those initially treated with intravenous corticosteroids. We identified independent predictors of outcome through multivariable logistic regression using a per-protocol approach. This study is registered with ClinicalTrials.gov, number NCT01536535. Findings Patients were recruited between July 10, 2012, and April 21, 2015. 428 children initiated mesalazine (n=136), oral corticosteroids (n=144), or intravenous corticosteroids (n=148). Initial mean PUCAI was 31·1 (SD 13·3) in children initiating with mesalazine, 50·4 (13·8) in those initiating oral corticosteroids, and 66·9 (13·7) in those initiating intravenous corticosteroids (p<0·0001 for between-group comparison). Week 12 outcome data were available for 132 patients who initiated with mesalazine, 141 with oral corticosteroids, and 143 with intravenous corticosteroids. Corticosteroid-free remission with the patient receiving mesalazine treatment only at 12 weeks was achieved by 64 (48%) patients in the mesalazine group, 47 (33%) in the oral corticosteroid group, and 30 (21%) in the intravenous corticosteroid group (p<0·0001). Treatment escalation was required by nine (7%) patients in the mesalazine group, 21 (15%) in the oral corticosteroid group, and 52 (36%) in the intravenous corticosteroid group (p<0·0001). Eight patients, all of whom were initially treated with intravenous corticosteroids, underwent colectomy. Predictors of week 12 corticosteroid-free remission were baseline PUCAI less than 35 (odds ratio 2·44, 95% CI 1·41–4·22; p=0·0015), higher baseline albumin by 1 g/dL increments among children younger than 12 years (4·05, 1·90–8·64; p=0·00030), and week 4 remission (6·26, 3·79–10·35; p<0·0001). Predictors of treatment escalation by week 12 in patients initially treated with intravenous corticosteroids included baseline total Mayo score of 11 or higher (2·59, 0·93–7·21; p=0·068 [retained in model due to clinical relevance]), rectal biopsy eosinophil count less than or equal to 32 cells per high power field (4·55, 1·62–12·78; p=0·0040), rectal biopsy surface villiform changes (3·05, 1·09–8·56; p=0·034), and not achieving week 4 remission (30·28, 6·36–144·20; p<0·0001). Interpretation Our findings provide guidelines to assess the response of children newly diagnosed with ulcerative colitis to standardised initial therapy and identify predictors of treatment response and failure. These data suggest that additional therapeutic interventions might be warranted to improve early outcomes, especially in patients presenting with severe disease and requiring intravenous corticosteroids. Funding National Institutes of Health.

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DO - 10.1016/S2468-1253(17)30252-2

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JO - The Lancet Gastroenterology and Hepatology

JF - The Lancet Gastroenterology and Hepatology

SN - 2468-1253

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