Evidence map›Paper›PMID 25011949›Full record

Trial reportDiabetes care2014

Low-dose otelixizumab anti-CD3 monoclonal antibody DEFEND-1 study: results of the randomized phase III study in recent-onset human type 1 diabetes.

Ronnie Aronson, Peter A Gottlieb, Jens S Christiansen, Thomas W Donner, Emanuele Bosi, Bruce W Bode, Paolo Pozzilli, DEFEND Investigator Group

Open access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes care, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 5 pooled it
8.6field-weighted citation impact, top 2% 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

83 citing papers in PubMed, 5 syntheses or guidelines pooled it, 149 citations in OpenAlex.

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  7. Nasal administration of anti-CD3 mAb (Foralumab) downregulatesProceedings of the National Academy of Sciences of the United States of America · 2023
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23 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

8 authors at 7 institutions in 4 countries.

Ronnie AronsonLMC Diabetes & Endocrinology, Toronto, Ontario, Canada ronnie.aronson@lmc.ca.
Peter A GottliebUniversity of Colorado, Denver, CO.
Jens S ChristiansenUniversity of Aarhus, Aarhus University Hospital, Aarhus, Denmark.
Thomas W DonnerJohns Hopkins University School of Medicine, Baltimore, MD.
Emanuele BosiSan Raffaele Hospital Scientific Institute, Vita Salute San Raffaele University, Milan, Italy.
Bruce W BodeEmory University, Atlanta Diabetes Associates, Atlanta, GA.
Paolo PozzilliUniversità Campus Bio-Medico di Roma, Rome, Italy Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, U.K.
DEFEND Investigator Group
Aarhus University Hospital · DKAtlanta Diabetes Associates · USJohns Hopkins Medicine · USLMC Diabetes & Endocrinology (Canada) · CAUniversità Campus Bio-Medico · ITUniversity of Colorado Denver · USVita-Salute San Raffaele University · IT

Funding

Impact of MHC Genotype on Ex Vivo T cell Function in Type 1 DiabetesDP3DK097681 · NIDDK · DANA-FARBER CANCER INST · PI LOVE, JOHN CHRISTOPHER, WUCHERPFENNIG, KAI W · 2012 to 2012
$3.9M
NIDDK NIH HHS DP3 DK097681
6 · The paper itself

Abstract

objectivePrevious studies demonstrated that the anti-CD3 monoclonal antibody otelixizumab, administered at a total dose of 48-64 mg, can slow the loss of C-peptide in recent-onset type 1 diabetes patients, with frequent reactivation of Epstein Barr virus (EBV). The DEFEND-1 (Durable Response Therapy Evaluation for Early or New-Onset Type 1 Diabetes) trial was designed to test whether a lower dose of otelixizumab could preserve C-peptide secretion in new-onset type 1 diabetes patients. RESEARCH DESIGN AND

methodsA multicenter, randomized, placebo-controlled trial was performed in sites in the U.S., Canada, and Europe. Two hundred eighty-one patients were randomized to treatment with 3.1 mg otelixizumab administered over 8 days or placebo. The primary end point of the study was the change in C-peptide area under the curve (AUC) from a 2-h mixed-meal tolerance test at month 12.

resultsThe change in 2-h C-peptide AUC was not different between placebo-treated patients and otelixizumab-treated patients (-0.20 vs. -0.22 nmol/L, P = 0.81). Secondary end points, including HbA1c, glucose variability, and insulin dose, were also not statistically different between the two groups. More patients in the otelixizumab group than in the placebo group experienced adverse events, mostly grade 1 or grade 2. There was no EBV reactivation (viral load >10,000 copies/10(6) peripheral blood mononuclear cells) in the otelixizumab group, in contrast with previously published studies at higher doses of otelixizumab.

conclusionsOtelixizumab was well tolerated in patients with recent-onset type 1 diabetes at a total dose of 3.1 mg, but did not achieve preservation of levels of C-peptide or other markers of metabolic control.

Indexed as

AdolescentAdultAge of OnsetAntibodies, Monoclonal, HumanizedCanadaCD3 ComplexChildC-PeptideDiabetes Mellitus, Type 1Dose-Response Relationship, DrugEuropeFemaleHumansHypoglycemic AgentsInsulinMaleAntibodies, Monoclonal, HumanizedCD3 ComplexC-PeptideHypoglycemic AgentsInsulinotelixizumab

Identifiers

PMID25011949
PMCPMC4392937
OpenAlexW2094345654

What OpenQuestion holds

Textmetadata
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.