title: Reduced brain atrophy rates are associated with lower risk of disability progression in patients with relapsing multiple sclerosis treated with cladribine tablets.
abstract: Neuroimaging 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.
  
  
  
  In 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).
  
  
  
  Compared 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.
  
  
  
  Cladribine 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.
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: De Stefano
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giorgio
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Battaglini
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Leucio
authors.affiliation: Global Biostatistics, Merck KGaA, Darmstadt, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Hicking
authors.affiliation: Global Clinical Development, EMD Serono, Inc., Billerica, MA, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Dangond
authors.affiliation: Department of Neurology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D017338:Cladribine / Q000008:administration & dosage / Q000494:pharmacology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology*; D017063:Outcome Assessment, Health Care; D012306:Risk; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D017338:Cladribine
keywords: Brain atrophy; CLARITY; brain volume; cladribine; disease progression; relapsing multiple sclerosis