Evidence map›Paper›PMID 23424159›Full record

Trial reportAnnals of neurology2013

Randomized study combining interferon and glatiramer acetate in multiple sclerosis.

Fred D Lublin, Stacey S Cofield, Gary R Cutter, Robin Conwit, Ponnada A Narayana, Flavia Nelson, Amber R Salter, Tarah Gustafson, Jerry S Wolinsky, CombiRx Investigators

Registry-linked trialOpen access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00211887 (A Multi-Center, Double-Blind, Randomized Study Comparing the Combined Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Patients With Relapsing-Remitting Multiple Sclerosis), which is not on this map. Cited by 95 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 11 pooled it
21.4field-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.

NCT00211887 phase3completednot on this map

A Multi-Center, Double-Blind, Randomized Study Comparing the Combined Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Patients With Relapsing-Remitting Multiple Sclerosis (CombiRx)

TypeinterventionalSponsorFred LublinRan2005 to 2013Enrolled1,008ConditionsRelapsing Remitting Multiple SclerosisArmsInterferon beta 1-a, glatiramer acetate, placebo
3 · Its place in the literature

Who cites it

95 citing papers in PubMed, 11 syntheses or guidelines pooled it, 200 citations in OpenAlex.

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  7. Comparative safety of high-efficacy disease-modifying therapies in relapsing-remitting multiple sclerosis: a systematic review and network meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022
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35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Fred D LublinCorinne Goldsmith Dickinson Center for Multiple Sclerosis, Department of Neurology, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. fred.lublin@mssm.edu
Stacey S Cofield
Gary R Cutter
Robin Conwit
Ponnada A Narayana
Flavia Nelson
Amber R Salter
Tarah Gustafson
Jerry S Wolinsky
CombiRx Investigators
The University of Texas Health Science Center at Houston · USUniversity of Alabama at Birmingham · USIcahn School of Medicine at Mount Sinai · USNational Institutes of Health · US

Funding

Extension of Combination Therapy for Multiple Sclerosis (eCombiRx)U01NS045719 · NINDS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI LUBLIN, FRED D · 2003 to 2012
$44.7M
Combination Therapy in Multiple SclerosisR21NS041986 · NINDS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI LUBLIN, FRED D · 2001 to 2001
$247k
NINDS NIH HHS R21 NS041986NINDS NIH HHS R21NS41986NINDS NIH HHS U01 NS045719NINDS NIH HHS UO1NS045719
6 · The paper itself

Abstract

objectiveA double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30 μg intramuscularly weekly and glatiramer acetate (GA) 20 mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis.

methodsA total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics.

resultsCombination IFN+GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results.

interpretationCombining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences.

Indexed as

AdolescentAdultAnalysis of VarianceCase-Control StudiesDisability EvaluationDouble-Blind MethodDrug Therapy, CombinationFemaleGlatiramer AcetateHumansImmunologic FactorsInterferon-betaLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedGlatiramer AcetateImmunologic FactorsInterferon-betaPeptides

Identifiers

PMID23424159
PMCPMC3631288
OpenAlexW1512495229

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.