Evidence map›Paper›PMID 25336114›Full record

Trial reportGut2015

The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease.

Niels Vande Casteele, Reena Khanna, Barrett G Levesque, Larry Stitt, G Y Zou, Sharat Singh, Steve Lockton, Scott Hauenstein, Linda Ohrmund, Gordon R Greenberg and 5 more

Registry-linked trialAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03773445 (Association of Golimumab Trough Levels With Endoscopic and Histologic Healing in Patients With Ulcerative Colitis), which is not on this map. Cited by 112 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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.

NCT03773445 completednot on this mapstarted 2019, after this paper: background citation

Association of Golimumab Trough Levels With Endoscopic and Histologic Healing in Patients With Ulcerative Colitis

TypeobservationalSponsorHospital San Carlos, MadridRan2019 to 2021Enrolled52ConditionsUlcerative ColitisArmsGolimumab trough levels, Antibodies to golimumab, Histology, Colonoscopy
3 · Its place in the literature

Who cites it

112 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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

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

15 authors.

Niels Vande CasteeleKU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium Division of Gastroenterology, University of California San Diego, La Jolla, California, USA Robarts Clinical Trials, Western University, London, Ontario, Canada.ORCID http://orcid.org/0000-0003-0854-0274
Reena KhannaRobarts Clinical Trials, Western University, London, Ontario, Canada.
Barrett G LevesqueDivision of Gastroenterology, University of California San Diego, La Jolla, California, USA Robarts Clinical Trials, Western University, London, Ontario, Canada.
Larry StittRobarts Clinical Trials, Western University, London, Ontario, Canada.
G Y ZouRobarts Clinical Trials, Western University, London, Ontario, Canada.
Sharat SinghPrometheus Laboratories, Inc., San Diego, California, USA.
Steve LocktonPrometheus Laboratories, Inc., San Diego, California, USA.
Scott HauensteinPrometheus Laboratories, Inc., San Diego, California, USA.
Linda OhrmundPrometheus Laboratories, Inc., San Diego, California, USA.
Gordon R GreenbergUniversity of Toronto, Mount Sinai Hospital, Toronto, Ontario, Canada.
Paul J RutgeertsKU Leuven Department of Clinical and Experimental Medicine, Leuven, Belgium.
Ann GilsKU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
William J SandbornDivision of Gastroenterology, University of California San Diego, La Jolla, California, USA.
Séverine VermeireKU Leuven Department of Clinical and Experimental Medicine, Leuven, Belgium.
Brian G FeaganRobarts Clinical Trials, Western University, London, Ontario, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveAlthough low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab.

designIn an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most discriminant for remission, defined as a C-reactive protein concentration of ≤ 5 mg/L, were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission.

resultsBased upon analysis of 1487 samples, 77.1% of patients had detectable and 22.9% had undetectable infliximab concentrations, of which 9.5% and 71.8%, respectively, were positive for ATI. An infliximab concentration of > 2.79 μg/mL (area under the curve (AUC) = 0.681; 95% CI 0.632 to 0.731) and ATI concentration of < 3.15 U/mL (AUC = 0.632; 95% CI 0.589 to 0.676) were associated with remission. Multivariable analysis showed that concentrations of both infliximab trough (OR 1.8; 95% CI 1.3 to 2.5; p < 0.001) and ATI (OR 0.57; 95% CI 0.39 to 0.81; p = 0.002) were independent predictors of remission.

conclusionsThe development of ATI increases the probability of active disease even at low concentrations and in the presence of a therapeutic concentration of drug during infliximab maintenance therapy. Evaluation of strategies to prevent ATI formation, including therapeutic drug monitoring with selective infliximab dose intensification, is needed.

Indexed as

AdultAntibodies, MonoclonalBiomarkersCrohn DiseaseDose-Response Relationship, DrugFemaleFollow-Up StudiesGastrointestinal AgentsHumansInfliximabMalePredictive Value of TestsPrognosisRemission InductionROC CurveSeverity of Illness IndexAntibodies, MonoclonalBiomarkersGastrointestinal AgentsInfliximabCROHN'S DISEASEINFLIXIMABPHARMACOKINETICSPHARMACOLOGYTNF

Identifiers

PMID25336114
PMCPMC4602247

What OpenQuestion holds

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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.