Evidence map›Paper›PMID 34951696›Full record

Trial reportBioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy2022

A Clinical Prediction Model to Determine Probability of Response to Certolizumab Pegol for Crohn's Disease.

Pavine L C Lefevre, Parambir S Dulai, Zhongya Wang, Leonardo Guizzetti, Brian G Feagan, Anca Pop, Mohamed Yassine, Lisa M Shackelton, Vipul Jairath, William J Sandborn and 1 more

Open access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 32% 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

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. 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

11 authors at 3 institutions in 3 countries.

Pavine L C LefevreAlimentiv, Inc., London, Ontario, Canada.
Parambir S DulaiDivision of Gastroenterology, University of California San Diego, 9500 Gilman Drive, #0956, La Jolla, CA, USA.
Zhongya WangAlimentiv, Inc., London, Ontario, Canada.
Leonardo GuizzettiAlimentiv, Inc., London, Ontario, Canada.
Brian G FeaganAlimentiv, Inc., London, Ontario, Canada.
Anca PopUCB Pharma, Smyrna, GA, USA.
Mohamed YassineUCB Pharma, Smyrna, GA, USA.
Lisa M ShackeltonAlimentiv, Inc., London, Ontario, Canada.
Vipul JairathAlimentiv, Inc., London, Ontario, Canada.
William J SandbornAlimentiv, Inc., London, Ontario, Canada.
Niels Vande CasteeleAlimentiv, Inc., London, Ontario, Canada. nvandecasteele@ucsd.edu.ORCID http://orcid.org/0000-0003-0854-0274
University of California San Diego · USUCB Pharma (United States) · USWestern University · CA

Funding

San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
NIDDK NIH HHS P30 DK120515
6 · The paper itself

Abstract

backgroundCertolizumab pegol (CZP) is effective for moderately to severely active Crohn's disease (CD). Higher plasma concentrations are associated with better outcomes and increased drug clearance is the driver of subtherapeutic CZP concentrations.

objectiveWe aimed to develop a prediction model incorporating predicted CZP clearance and patient variables to allow estimation of the probability for remission prior to initiating therapy.

methodsA population pharmacokinetic model estimated baseline CZP clearance in patients with CD from nine phase II and III trials. Multivariable prediction models were developed and validated using the PRECiSE 1 and PRECiSE 2 datasets to identify candidate predictors for a composite remission outcome (Crohn's Disease Activity Index ≤ 150 and fecal calprotectin concentration ≤ 250 μg/g) at Weeks 6 or 26. An online clinical decision support tool (CDST) was developed.

resultsBaseline predicted CZP clearance ≥ 0.5 L/day was associated with subtherapeutic Week 6 CZP plasma concentrations. Baseline weight (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.02-1.07), calculated CZP clearance (OR 0.92; 95% CI 0.87-0.96), hematocrit (OR 2.55; 95% CI 1.43-4.54), and fecal calprotectin (OR 0.66; 95% CI 0.54-0.80) were associated with Week 6 remission (p ≤ 0.0015 for all predictors). Baseline weight (OR 1.04; 95% CI 1.02-1.07), calculated CZP clearance (OR 0.93; 95% CI 0.88-0.97), and Patient-Reported Outcome-2 (PRO2) (OR 0.93; 95% CI 0.87-0.99) were associated with Week 26 remission (p ≤ 0.033 for all predictors).

conclusionsPatients who are predicted to have accelerated baseline CZP clearance are at risk of subtherapeutic CZP concentrations. Patient-level probabilities for a composite remission outcome can be predicted for patients with CD by entering commonly available patient- and disease-related factors into an online CDST ( https://premedibd.com ) incorporating predicted CZP clearance.

Indexed as

Crohn DiseaseCertolizumab PegolHumansModels, StatisticalProbabilityPrognosisTreatment OutcomeCertolizumab Pegol

Identifiers

PMID34951696
PMCPMC9826742
OpenAlexW4200032396

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.