Oral Cladribrine Treatment Reduces Brain Atrophy Rates in Relapsing-Remitting Multiple Sclerosis: Exploratory Analysis of the CLARITY Study (P07.112)

OBJECTIVE: To evaluate the effect of oral cladribine on brain atrophy as assessed by magnetic resonance imaging (MRI) in patients with relapsing-remitting multiple sclerosis (RRMS) from the CLARITY study. BACKGROUND: The CLARITY study, a double-blind 96-week phase-3 trial of short-course oral therapy with cladribine demonstrated efficacy on clinical relapses and focal MRI lesions in RRMS patients. Global MRI measures of brain volume changes can provide a good measure of tissue atrophy rates, which is an expression of neuro-axonal integrity loss, gliosis, demyelination and possibly remyelination. DESIGN/METHODS: 1326 RRMS patients aged 18–55 years were randomized 1:1:1 to 5.25mg/kg cladribine, 3.5mg/kg cladribine, or placebo for 96 weeks. Brain atrophy measurements were performed on T1-weighted MRI data by using the SIENA method and expressed as percent brain volume change (PBVC) over the 96 weeks of treatment. Data were calculated using week-24 as baseline to avoid confounding factors such as delayed treatment effect and resolution of inflammation (i.e., pseudoatrophy). RESULTS: Brain atrophy assessments were performed for 889 cladribine treated patients and 437 placebo treated patients from CLARITY. The mean±SD PBVC from week 24 to week 96 was -0.77±0.95 for the combined cladribine treated group and -0.95 ±1.0 for the placebo group (p=0.002). There were no differences in PBVC between the two treatment regimens of cladribine (-0.77±0.96 with the 5.25 mg/kg dosage and -0.77±0.94 with the 3.5 mg/kg dosage). CONCLUSIONS: This exploratory analysis shows that treatment with cladribine tablets significantly reduced brain atrophy rates 24 weeks after its first assumption and for as long as 96 weeks. This additional benefit of this oral treatment for RRMS should be weighed against the risks. Supported by: Merck Serono S.A. – Geneva, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany. Disclosure: Dr. De Stefano has received personal compensation for activities with Merck Serono, Novartis, Teva Neuroscience, and BioMS. Dr. Giorgio has nothing to disclose. Dr. De Leucio has nothing to disclose. Dr. Hamlett has received personal compensation for activities with EMD Serono as an employee. Dr. Scaramozza has received personal compensation for activities with Pfizer research, employed by inVentiv Clinical Solutions, Inc. as an onsite consultant. Dr. Stubinski has received personal compensation for activities with Merck Serono S.A. as an employee.