Evidence map›Paper›PMID 24535134›Full record

Trial reportJournal of neurology2014

A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis.

T L Vollmer, P S Sorensen, K Selmaj, F Zipp, E Havrdova, J A Cohen, N Sasson, Y Gilgun-Sherki, D L Arnold, BRAVO Study Group

Abstract readClinical Trial, Phase IIIComparative StudyMulticenter Study
PubMed Publisher
In one paragraph

Trial report in Journal of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 11 pooled it
15.2field-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.

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

94 citing papers in PubMed, 11 syntheses or guidelines pooled it, 194 citations in OpenAlex.

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  6. 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
    Pooled it
  7. Efficacy and acceptability of the S1P receptor in the treatment of multiple sclerosis: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021
    Pooled it
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  12. Trial
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  18. Brain atrophy rates vary with age in relapsing-remitting multiple sclerosis.Journal of neurology, neurosurgery, and psychiatry · 2026
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34 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

10 authors at 6 institutions in 7 countries.

T L VollmerDepartment of Neurology, University of Colorado, Aurora, CO, USA, timothy.vollmer@ucdenver.edu.
P S Sorensen
K Selmaj
F Zipp
E Havrdova
J A Cohen
N Sasson
Y Gilgun-Sherki
D L Arnold
BRAVO Study Group
Cleveland Clinic · USJohannes Gutenberg University Mainz · DETeva Pharmaceuticals (Israel) · ILUniversity of Copenhagen · DKNeuroRx Research (Canada) · CARocky Mountain MS Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS (RRMS), and descriptively compared laquinimod with interferon beta (IFNβ)-1a (Avonex(®) reference arm). RRMS patients age 18-55 years with Expanded Disability Status Scale (EDSS) scores of 0-5.5 and documented pre-study relapse (≥ 1 in previous year, 2 in previous 2 years, or 1 in previous 1-2 years and ≥ 1 GdE lesion in the previous year) were randomized (1:1:1) to laquinimod 0.6 mg once-daily, matching oral placebo, or IFNβ-1a IM 30 μg once-weekly (rater-blinded design), for 24 months. The primary endpoint was annualized relapse rate (ARR); secondary endpoints included percent brain volume change (PBVC) and 3-month confirmed disability worsening. In all, 1,331 patients were randomized: laquinimod (n = 434), placebo (n = 450), and IFNβ-1a (n = 447). ARR was not significantly reduced with laquinimod [-18 %, risk ratio (RR) = 0.82, 95 % CI 0.66-1.02; p = 0.075] vs. placebo. Laquinimod significantly reduced PBVC (28 %, p < 0.001). Confirmed disability worsening was infrequent (10 % laquinimod, 13 % placebo). The change in confirmed disability worsening with laquinimod measured using EDSS was -31 % [hazard ratio (HR) 0.69, p = 0.063], and using Multiple Sclerosis Functional Composite (MSFC) z-score was -77 % (p = 0.150), vs. placebo. IFNβ-1a reduced ARR 26 % (RR = 0.74, 95 % CI 0.60-0.92, p = 0.007), showed no effect on PBVC loss (+11 %, p = 0.14), and changes in disability worsening were -26 and -66 % as measured using the EDSS (HR 0.742, p = 0.13) and MSFC (p = 0.208), respectively. Adverse events occurred in 75, 82, and 70 % of laquinimod, IFNβ-1a, and placebo patients, respectively. Once-daily oral laquinimod 0.6 mg resulted in statistically nonsignificant reductions in ARR and disability progression, but significant reductions in brain atrophy vs. placebo. Laquinimod was well-tolerated.

Indexed as

AdolescentAdultEndpoint DeterminationFemaleHumansInterferon-betaMaleMiddle AgedMultiple SclerosisQuinolonesRecurrenceRisk AssessmentYoung AdultInterferon-betalaquinimodQuinolones

Identifiers

PMID24535134
OpenAlexW2011324376

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.