Evidence map›Paper›PMID 28140753›Full record

Trial reportMultiple sclerosis (Houndmills, Basingstoke, England)2018

Reduced brain atrophy rates are associated with lower risk of disability progression in patients with relapsing multiple sclerosis treated with cladribine tablets.

Nicola De Stefano, Antonio Giorgio, Marco Battaglini, Alessandro De Leucio, Christine Hicking, Fernando Dangond, Gavin Giovannoni, Maria Pia Sormani

2 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Multiple sclerosis (Houndmills, Basingstoke, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 40 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 3 pooled it
6.3field-weighted citation impact, top 3% 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.

NCT00213135 phase3completednot on this map

A Phase III, Randomized, Double-blind, Three-arm, Placebo-controlled, Multi-center Study to Evaluate the Safety and Efficacy of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)

TypeinterventionalSponsorEMD SeronoRan2005 to 2008Enrolled1,326ConditionsMultiple Sclerosis, Relapsing-RemittingArmsCladribine 5.25 mg/kg, Cladribine 3.5 mg/kg, Placebo
NCT04178005 phase4active not recruitingnot on this mapstarted 2020, after this paper: background citation

Cladribine Tablets After Treatment With Natalizumab (CLADRINA)

TypeinterventionalSponsorUniversity of Texas Southwestern Medical CenterRan2020 to 2026Enrolled40ConditionsMultiple SclerosisArmsCladribine
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 65 citations in OpenAlex.

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  13. Cladribine tablets in the new multiple sclerosis era.Therapeutic advances in neurological disorders · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 3 countries.

Nicola De StefanoDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Antonio GiorgioDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Marco BattagliniDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Alessandro De LeucioDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Christine HickingGlobal Biostatistics, Merck KGaA, Darmstadt, Germany.
Fernando DangondGlobal Clinical Development, EMD Serono, Inc., Billerica, MA, USA.
Gavin GiovannoniDepartment of Neurology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Maria Pia SormaniBiostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
University of Siena · ITMerck (Germany) · DEQueen Mary University of London · GBUniversity of Genoa · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeuroimaging studies have used magnetic resonance imaging-derived methods to assess brain volume loss in multiple sclerosis (MS) as a reliable measure of diffuse tissue damage.

methodsIn the CLARITY study ( ClinicalTrials.gov NCT00213135), the effect of 2 years' treatment with cladribine tablets on annualized percentage brain volume change (PBVC/y) was evaluated in patients with relapsing MS (RMS).

resultsCompared with placebo (-0.70% ± 0.79), PBVC/y was reduced in patients treated with cladribine tablets 3.5 mg/kg (-0.56% ± 0.68, p = 0.010) and 5.25 mg/kg (-0.57% ± 0.72, p = 0.019). After adjusting for treatment group, PBVC/y showed a significant correlation with the cumulative probability of disability progression (HR = 0.67, 95% CI = 0.571, 0.787; p < 0.001), with patients with lower PBVC/y showing the highest probability of remaining free from disability progression at 2 years and vice versa.

conclusionsCladribine tablets given annually for 2 years in short-duration courses in patients with RMS in the CLARITY study significantly reduced brain atrophy in comparison with placebo treatment, with residual rates in treated patients being close to the physiological rates.

Indexed as

Disease ProgressionOutcome Assessment, Health CareAdolescentAdultAgedAtrophyBrainCladribineFemaleHumansImmunosuppressive AgentsMaleMiddle AgedMultiple Sclerosis, Relapsing-RemittingRiskYoung AdultCladribineImmunosuppressive AgentsBrain atrophybrain volumecladribineCLARITYdisease progressionrelapsing multiple sclerosis

Identifiers

PMID28140753
PMCPMC5818021
OpenAlexW2583686943

What OpenQuestion holds

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LicenceCC BY-NC
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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.