Evidence map›Paper›PMID 30901380›Full record

Trial reportJournal of Crohn's & colitis2019

Molecular Profiling of Ulcerative Colitis Subjects from the TURANDOT Trial Reveals Novel Pharmacodynamic/Efficacy Biomarkers.

Huanyu Zhou, Li Xi, Daniel Ziemek, Shawn O'Neil, Julie Lee, Zachary Stewart, Yutian Zhan, Shanrong Zhao, Ying Zhang, Karen Page and 11 more

Open access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of Crohn's & colitis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 1 institution in 1 country.

Huanyu ZhouPfizer, Cambridge, MA, USA.
Li XiPfizer, Cambridge, MA, USA.
Daniel ZiemekPfizer, Cambridge, MA, USA.
Shawn O'NeilPfizer, Cambridge, MA, USA.
Julie LeePfizer, Cambridge, MA, USA.
Zachary StewartPfizer, Cambridge, MA, USA.
Yutian ZhanPfizer, Cambridge, MA, USA.
Shanrong ZhaoPfizer, Cambridge, MA, USA.
Ying ZhangPfizer, Cambridge, MA, USA.
Karen PagePfizer, Cambridge, MA, USA.
Austin HuangPfizer, Cambridge, MA, USA.
Mateusz MaciejewskiPfizer, Cambridge, MA, USA.
Baohong ZhangPfizer, Cambridge, MA, USA.
Kenneth J GorelickPfizer, Cambridge, MA, USA.
Lori FitzPfizer, Cambridge, MA, USA.
Vivek PradhanPfizer, Cambridge, MA, USA.
Fabio CataldiPfizer, Cambridge, MA, USA.
Michael VincentPfizer, Cambridge, MA, USA.
David Von SchackPfizer, Cambridge, MA, USA.
Kenneth HungPfizer, Cambridge, MA, USA.
Mina Hassan-ZahraeePfizer, Cambridge, MA, USA.
Pfizer (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsTo define pharmacodynamic and efficacy biomarkers in ulcerative colitis [UC] patients treated with PF-00547659, an anti-human mucosal addressin cell adhesion molecule-1 [MAdCAM-1] monoclonal antibody, in the TURANDOT study.

methodsTranscriptome, proteome and immunohistochemistry data were generated in peripheral blood and intestinal biopsies from 357 subjects in the TURANDOT study.

resultsIn peripheral blood, C-C motif chemokine receptor 9 [CCR9] gene expression demonstrated a dose-dependent increase relative to placebo, but in inflamed intestinal biopsies CCR9 gene expression decreased with increasing PF-00547659 dose. Statistical models incorporating the full RNA transcriptome in inflamed intestinal biopsies showed significant ability to assess response and remission status. Oncostatin M [OSM] gene expression in inflamed intestinal biopsies demonstrated significant associations with, and good accuracy for, efficacy, and this observation was confirmed in independent published studies in which UC patients were treated with infliximab or vedolizumab. Compared with the placebo group, intestinal T-regulatory cells demonstrated a significant increase in the intermediate 22.5-mg dose cohort, but not in the 225-mg cohort.

conclusionsCCR9 and OSM are implicated as novel pharmacodynamic and efficacy biomarkers. These findings occur amid coordinated transcriptional changes that enable the definition of surrogate efficacy biomarkers based on inflamed biopsy or blood transcriptomics data.ClinicalTrials.gov identifierNCT01620255.

Indexed as

Antibodies, Monoclonal, HumanizedBiomarkersCell Adhesion Molecule-1Colitis, UlcerativeColonDose-Response Relationship, DrugDouble-Blind MethodGene Expression ProfilingHumansProteomicsTreatment OutcomeAntibodies, Monoclonal, HumanizedBiomarkersCADM1 protein, humanCell Adhesion Molecule-1ontamalimabbiomarkersinflammatory bowel diseaseMAdCAM-1PF-00547659Ulcerative colitis

Identifiers

PMID30901380
PMCPMC6535501
OpenAlexW2947222449

What OpenQuestion holds

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Registered trials

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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.