Multiple Sclerosis: clinical aspectsMonday, June 22, 2009, 14:15 - 14:30Clinical efficacy of cladribine tablet therapy in patients with relapsing-remitting multiple sclerosis (RRMS): results from the CLARITY study, a 96-week, phase III, double-blind, placebo-controlled trialG. Giovannoni, G. Comi, S. Cook, 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. Here we assess the clinical efficacy of cladribine tablets vs. placebo in patients with RRMS.
Methods: In the CLARITY (CLAdRIbine tablets Treating multiple sclerosis orallY) study, patients with RRMS (McDonald criteria; Expanded Disability Status Scale [EDSS] score 0-5.5) were randomised 1:1:1 to receive placebo or a cumulative dose of 5.25 or 3.5 mg/kg cladribine tablets. Four (5.25 mg/kg arm) or two (3.5 mg/kg arm) courses of 0.875 mg/kg were administered over 4-5 days in Weeks 1, 5, 9 and 13; or Weeks 1 and 5, respectively. Two further short courses were administered in Weeks 48 and 52, to both active arms. The primary efficacy endpoint was qualifying relapse rate over 96 weeks, analyzed using a Poisson regression model.
Results: 1326 patients were randomised to 5.25 or 3.5 mg/kg cladribine tablets or placebo (ITT population; n=456, 433 and 437, respectively). Groups were comparable for baseline characteristics, including age, gender and relapse rate in the 48 weeks prior to treatment. Cladribine treatment resulted in significant reductions in the annualised rate of qualifying relapses to Week 96 (0.15 and 0.14 vs. 0.33 in the 5.25 and 3.5 mg/kg groups vs. placebo; relative reduction 55% and 58%, respectively, both p<0.001). In addition, significantly more patients were relapse-free at Week 96 in the 5.25 and 3.5 mg/kg groups vs. placebo (79% and 80% vs. 61%), with a relative risk to relapse of 0.54 and 0.52, respectively (both p<0.001). The risk of 3-month sustained disability progression was also significantly reduced, with a hazard ratio for relative reduction vs. placebo of 0.69 (95% CI: 0.49, 0.96; p=0.026) for cladribine 5.25 mg/kg and 0.67 (95% CI: 0.48, 0.93; p=0.018) for cladribine 3.5 mg/kg. This was accompanied by significant improvements in MRI outcomes and good safety and tolerability, as reported elsewhere.
Conclusions: Treatment with cladribine tablets in the CLARITY study resulted in a significant reduction in relapse rates and prolonged time to sustained disability progression relative to placebo. When taken alongside the MRI and safety data, the results provide clear evidence supporting the use of cladribine tablets in the treatment of RRMS.
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