title: MRI outcomes with cladribine tablets for multiple sclerosis in the CLARITY study.
abstract: We herein provide a comprehensive assessment of magnetic resonance imaging (MRI) outcomes from CLARITY, a 96-week, double-blind study demonstrating significant clinical and MRI improvements in patients with relapsing-remitting multiple sclerosis (RRMS) treated with cladribine tablets. Patients with RRMS were randomized 1:1:1 to annual short-course therapy with cladribine tablets cumulative dose 3.5 or 5.25 mg/kg or placebo. MRI endpoints included mean number of T1 gadolinium-enhancing (Gd+), active T2 and combined unique (CU) lesions/patient/scan. MRI-measured disease activity was significantly reduced in both cladribine tablets groups versus placebo. The proportion of patients with no active lesions at study end was: T1 Gd+ lesions: 86.8 and 91.0 versus 48.3 % (p < 0.001); active T2 lesions: 61.7 and 62.5 versus 28.4 % (p < 0.001); CU lesions: 59.6 and 60.7 versus 26.1 % (p < 0.001). Clinically meaningful and significant reductions in active lesion counts and increases in proportions of active lesion-free patients were achieved consistently in cladribine tablet groups when data were stratified by baseline disease characteristics. For example, the percentage of patients who remained lesion-free over the study was significantly greater in cladribine tablet groups than in the placebo group for all lesion types regardless of relapse category at baseline (p < 0.001 for all analyses of patients with ≤1 or 2 relapses; p ≤ 0.022 for analyses of patients with ≥3 relapses). MRI-measured disease activity was greatly reduced by both doses of cladribine tablets, with consistent effect across clinically relevant patient populations. These findings add to our scientific understanding of the neurological impact of this therapeutic modality in patients with RRMS.
authors.affiliation: Department of Neurology and Institute of Experimental Neurology, Scientific Institute H.S. Raffaele, Università Vita-Salute San Raffaele, via Olgettina 60, 20132 Milan, Italy. comi.giancarlo@hsr.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Cook
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.forename: Kottil
authors.initials: K
authors.lastname: Rammohan
authors.forename: Peter
authors.initials: P
authors.lastname: Rieckmann
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sørensen
authors.forename: Patrick
authors.initials: P
authors.lastname: Vermersch
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Hamlett
authors.forename: Vissia
authors.initials: V
authors.lastname: Viglietta
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Greenberg
mesh_terms: D000704:Analysis of Variance; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D017338:Cladribine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005682:Gadolinium; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology*; D055502:Secondary Prevention; D012720:Severity of Illness Index; D013607:Tablets / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D013607:Tablets; D017338:Cladribine; D005682:Gadolinium