Evidence map›Paper›PMID 30935734›Full record

Trial reportLancet (London, England)2019

Clinical and biological predictors of response to standardised paediatric colitis therapy (PROTECT): a multicentre inception cohort study.

Jeffrey S Hyams, Sonia Davis Thomas, Nathan Gotman, Yael Haberman, Rebekah Karns, Melanie Schirmer, Angela Mo, David R Mack, Brendan Boyle, Anne M Griffiths and 40 more

Registry-linked trialOpen access · greenAbstract readClinical TrialComparative StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01536535 (Multicenter Open-label Study Evaluating the Safety and Efficacy of Standardized Initial Therapy Using Either Mesalamine or Corticosteroids Then Mesalamine to Treat Children and Adolescents With Newly Diagnosed Ulcerative Colitis.), which is not on this map. Cited by 84 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 2 pooled it
15.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01536535 phase4completednot on this map

Multicenter Open-label Study Evaluating the Safety and Efficacy of Standardized Initial Therapy Using Either Mesalamine or Corticosteroids Then Mesalamine to Treat Children and Adolescents With Newly Diagnosed Ulcerative Colitis.

TypeinterventionalSponsorConnecticut Children's Medical CenterRan2012 to 2018Enrolled431ConditionsUlcerative ColitisArmsMesalazine, IV Corticosteroid, Oral Corticosteroids, Additional Therapies, Colectomy
3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 162 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Trial
  4. Trial
  5. Immunoglobulin A protease fromGut microbes · 2026
    Article
  6. A Novel Cationic Antimicrobial Peptide ScymidgutinProbiotics and antimicrobial proteins · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review

24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

50 authors at 20 institutions in 3 countries.

Jeffrey S HyamsDivision of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, CT, USA. Electronic address: jhyams@connecticutchildrens.org.
Sonia Davis ThomasCollaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, NC, USA; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA; RTI International, Research Triangle Park, NC, USA.
Nathan GotmanCollaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, NC, USA.
Yael HabermanDivision of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA; Sheba Medical Center, affiliated with the Tel Aviv University, Tel Hashomer, Israel.
Rebekah KarnsDivision of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Melanie SchirmerThe Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, MA, USA.
Angela MoGeorgia Institute of Technology, Atlanta, GA, USA.
David R MackSchool of Biological Sciences, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
Brendan BoyleDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, OH, USA.
Anne M GriffithsDivisioin of Pediatric Gastroenterology, Hospital For Sick Children, Toronto, ON, Canada.
Neal S LeLeikoIBD Centre, Department of Paediatrics, Hasbro Children's Hospital, Providence, RI, USA.
Cary G SauerDivisioin of Pediatric Gastroenterology, Nutritiion, and Liver Disease, Emory University, Atlanta, GA, USA.
David J KeljoDivision of Gastroenterology, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
James MarkowitzDivision of Gastroenterology, Hepatology, and Nutrition, Cohen Children's Medical Center Of New York, New Hyde Park, NY, USA.
Susan S BakerDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Women & Children's Hospital of Buffalo WCHOB, Buffalo, NY, USA.
Joel RoshDivision of Gastroenterology, Hepatology, and Nutrition, Goryeb Children's Hospital, Atlantic Health, Morristown, NJ, USA.
Robert N BaldassanoDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Ashish PatelDivision of Gastroenterology, Hepatology, and Nutrition, UT Southwestern, Dallas, TX, USA.
Marian PfefferkornDivision of Gastroenterology, Hepatology, and Nutrition, Riley Children's Hospital Indiana, Indianapolis, IN, USA.
Anthony OtleyDivision of Gastroenterology, Hepatology, and Nutrition, IWK Health Centre, Halifax, NS, Canada.
Melvin HeymanDivision of Gastroenterology, Hepatology, and Nutrition, University of California at San Francisco, San Francisco, CA, USA.
Joshua NoeDivision of Gastroenterology, Hepatology, and Nutrition, Medical College of Wisconsin, Milwaukee, WI, USA.
Maria Oliva-HemkerDivision of Gastroenterology, Hepatology, and Nutrition, Johns Hopkins Children's Center, Baltimore, MD, USA.
Paul A RufoDivision of Gastroenterology, Hepatology, and Nutrition, Children's Hospital Boston, Harvard Medical School Boston, MA, USA.
Jennifer StropleDivision of Gastroenterology, Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA.
David ZiringDivision of Gastroenterology, Hepatology, and Nutrition, UCLA Medical Center, Los Angeles, CA, USA.
Stephen L GutheryDivision of Gastroenterology, Hepatology, and Nutrition, Primary Children's Hospital and the University of Utah, Salt Lake City, UT, USA.
Boris SudelDivision of Gastroenterology, Hepatology, and Nutrition, University of Minnesota Medical Center, Minneapolis, MN, USA.
Keith BenkovDivision of Gastroenterology, Hepatology, and Nutrition, Mt Sinai Hospital, New York City, NY, USA.
Prateek WaliDivision of Gastroenterology, Hepatology, and Nutrition, State University of New York Upstate Medical University, Syracuse, NY, USA.
Dedrick MoultonDivision of Gastroenterology, Hepatology, and Nutrition, Monroe Carell Jr Children's Hospital of Vanderbilt, Nashville, TN, USA.
Jonathan EvansDivision of Gastroenterology, Hepatology, and Nutrition, Nemours Children's Clinic, Jacksonville, FL, USA.
Michael D KappelmanDepartment of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.
M Alison MarquisCollaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, NC, USA.
Francisco A SylvesterDepartment of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.
Margaret H CollinsDivision of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Suresh VenkateswaranDivisioin of Pediatric Gastroenterology, Nutritiion, and Liver Disease, Emory University, Atlanta, GA, USA.
Marla DubinskyDivision of Gastroenterology, Hepatology, and Nutrition, Mt Sinai Hospital, New York City, NY, USA.
Vin TangprichaDivisioin of Pediatric Gastroenterology, Nutritiion, and Liver Disease, Emory University, Atlanta, GA, USA.
Krista L SpadaDivision of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, CT, USA.
Bradley SaulCollaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, NC, USA.
Jessie WangCollaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, NC, USA.
Jose SerranoNational Institutes of Diabetes, Digestive and Kidney Diseases, Bethesda, MD, USA.
Kevin HommelDivision of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Urko M MarigortaGeorgia Institute of Technology, Atlanta, GA, USA.
Greg GibsonGeorgia Institute of Technology, Atlanta, GA, USA.
Ramnik J XavierThe Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Computational and Integrative Biology, Gastrointestinal Unit, and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA.
Subra KugathasanDivisioin of Pediatric Gastroenterology, Nutritiion, and Liver Disease, Emory University, Atlanta, GA, USA.
Thomas WaltersDivisioin of Pediatric Gastroenterology, Hospital For Sick Children, Toronto, ON, Canada.
Lee A DensonDivision of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
University of Cincinnati · USEmory University · USThe Coordinating Center · USGeorgia Institute of Technology · USConnecticut Children's Medical Center · USHospital for Sick Children · CASinai Hospital · USUniversity of North Carolina at Chapel Hill · USBroad Institute · USChildren's Hospital of Eastern Ontario · CAChildren's Hospital of Philadelphia · USChildren's Hospital of Pittsburgh · USCohen Children's Medical Center · USGoryeb Children's Hospital · USHarvard University · USHasbro Children's Hospital · USIzaak Walton Killam Health Centre · CAJohns Hopkins University · USLurie Children's Hospital · USMassachusetts General Hospital · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
Predicting Response to Standardized Pediatric Colitis Therapy: PROTECT StudyU01DK095745 · NIDDK · CONNECTICUT CHILDREN'S MEDICAL CENTER · PI DENSON, LEE ARMISTEAD, HYAMS, JEFFREY SAMUEL · 2012 to 2016
$10.4M
Identification and characterization of gut microbial bioactive molecules that determine predisposition to autoimmune disease and atopyR01AT009708 · NCCIH · HARVARD MEDICAL SCHOOL · PI CLARDY, JON, XAVIER, RAMNIK J · 2017 to 2021
$3.3M
NCCIH NIH HHS R01 AT009708NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30 DK078392NIDDK NIH HHS U01 DK095745
6 · The paper itself

Abstract

backgroundLack of evidence-based outcomes data leads to uncertainty in developing treatment regimens in children who are newly diagnosed with ulcerative colitis. We hypothesised that pretreatment clinical, transcriptomic, and microbial factors predict disease course.

methodsIn this inception cohort study, we recruited paediatric patients aged 4-17 years with newly diagnosed ulcerative colitis from 29 centres in the USA and Canada. Patients initially received standardised mesalazine or corticosteroids, with pre-established criteria for escalation to immunomodulators (ie, thiopurines) or anti-tumor necrosis factor-α (TNFα) therapy. We used RNA sequencing to define rectal gene expression before treatment, and 16S sequencing to characterise rectal and faecal microbiota. The primary outcome was week 52 corticosteroid-free remission with no therapy beyond mesalazine. We assessed factors associated with the primary outcome using logistic regression models of the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01536535.

findingsBetween July 10, 2012, and April 21, 2015, of 467 patients recruited, 428 started medical therapy, of whom 400 (93%) were evaluable at 52 weeks and 386 (90%) completed the study period with no protocol violations. 150 (38%) of 400 participants achieved week 52 corticosteroid-free remission, of whom 147 (98%) were taking mesalazine and three (2%) were taking no medication. 74 (19%) of 400 were escalated to immunomodulators alone, 123 (31%) anti-TNFα therapy, and 25 (6%) colectomy. Low baseline clinical severity, high baseline haemoglobin, and week 4 clinical remission were associated with achieving week 52 corticosteroid-free remission (n=386, logistic model area under the curve [AUC] 0·70, 95% CI 0·65-0·75; specificity 77%, 95% CI 71-82). Baseline severity and remission by week 4 were validated in an independent cohort of 274 paediatric patients with newly diagnosed ulcerative colitis. After adjusting for clinical predictors, an antimicrobial peptide gene signature (odds ratio [OR] 0·57, 95% CI 0·39-0·81; p=0·002) and abundance of Ruminococcaceae (OR 1·43, 1·02-2·00; p=0·04), and Sutterella (OR 0·81, 0·65-1·00; p=0·05) were independently associated with week 52 corticosteroid-free remission.

interpretationOur findings support the utility of initial clinical activity and treatment response by 4 weeks to predict week 52 corticosteroid-free remission with mesalazine alone in children who are newly diagnosed with ulcerative colitis. The development of personalised clinical and biological signatures holds the promise of informing ulcerative colitis therapeutic decisions.

fundingUS National Institutes of Health.

Indexed as

AdolescentAdrenal Cortex HormonesAnti-Inflammatory Agents, Non-SteroidalBiomarkersChildChild, PreschoolCohort StudiesColitis, UlcerativeFemaleHospitalizationHumansMaleMesalamineTreatment OutcomeAdrenal Cortex HormonesAnti-Inflammatory Agents, Non-SteroidalBiomarkersMesalamine

Identifiers

PMID30935734
PMCPMC6501846
OpenAlexW2935449958

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.