Multiple sclerosis: treatmentTuesday, June 23, 2009, 17:15 - 17:30Magnetic resonance imaging (MRI) outcomes in patients with relapsing–remitting multiple sclerosis (RRMS) treated with cladribine tablets: results from the CLARITY study, a 96-week, phase III, double-blind, placebo-controlled trialG. Comi, S. Cook, G. Giovannoni, K. Rammohan, P. Rieckmann, P. Soelberg-Sørensen, P. Vermersch, P. Chang, A. Hamlett, B. Musch, T. Fevr, S. Greenberg on behalf of the CLARITY Study Group
Objectives: Cladribine tablets are in development for the treatment of multiple sclerosis. Cladribine is a pro-drug, and activation in specific cell types provides targeted and sustained immunomodulation, permitting the investigation of an oral short-course annual treatment. We evaluated the MRI outcomes of cladribine tablets vs. placebo for patients with RRMS, in a 96-week, randomised, double-blind, 3-arm, placebo-controlled, multicentre study: the CLARITY (CLAdRIbine tablets Treating multiple sclerosis orallY) study.
Methods: Patients with RRMS (McDonald criteria; Expanded Disability Status Scale [EDSS] score 0 to 5.5) were randomised to 2 dosing regimens of cladribine tablets (cumulative doses of 5.25 or 3.5 mg/kg), or matching placebo (1:1:1). Cladribine tablets were given as short courses (once daily for 4-5 days) in Weeks 1, 5, 9 and 13 (5.25 mg/kg arm) or Weeks 1 and 5 (3.5 mg/kg arm), and again in Weeks 48 and 52 (both arms). Prespecified secondary MRI endpoints over 96 weeks included number of T1 Gd+ lesions, number of active T2 lesions and number of combined unique lesions (CU)/patient/scan. MRI data were evaluated using a non-parametric analysis of covariance (ANCOVA) model adjusting for treatment, region and baseline lesion counts.
Results: In the ITT population, 456, 433 and 437 patients were randomised to 5.25 or 3.5 mg/kg cladribine tablets or placebo, respectively; groups were comparable for baseline characteristics, including number of T1 Gd+ lesions (mean 1.0, 1.0 and 0.8), and T2 lesion volume (mean 17.2, 14.8 and 14.3 mL, respectively). Cladribine-treated patients in 5.25 or 3.5 mg/kg groups had significantly less disease activity on neuroimaging assessment compared to placebo-treated patients, exemplified by 87.9% and 85.7% relative reductions in T1 Gd-enhancing lesions (mean 0.11 and 0.12 vs. 0.91), 76.9% and 73.4% relative reductions in active T2 lesions (mean 0.33 and 0.38 vs. 1.43), and 77.9% and 74.4% relative reductions in CU lesions (mean 0.38 and 0.43 vs. 1.72 lesions per subject per scan), respectively; all p<0.001 vs. placebo. This highly significant cladribine-related treatment effect on MRI was evident at Weeks 24, 48 and 96 of study.
Conclusions: Brain MRI activity is greatly reduced by cladribine at both dosing regimens. The effects on MRI activity mirror the clinical benefits reported with cladribine tablets, supporting the key role of the drug in the treatment of RRMS
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