Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study

Background: In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS). Objective: To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. Methods: In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5mg/kg or placebo, with blind maintained. Results: A total of 806 patients were assigned to treatment. Adverse event rates were generally similar between groups, but lymphopenia Grade3 rates were higher with cladribine than placebo (Grade 4 lymphopenia occurred infrequently). In patients receiving cladribine 3.5mg/kg in CLARITY and experiencing lymphopenia Grade3 in the Extension, >90% of those treated with cladribine 3.5mg/kg and all treated with placebo in the Extension, recovered to Grade 0-1 by study end. Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension; in patients treated with cladribine 3.5mg/kg in CLARITY, approximately 75% remained relapse-free when given placebo during the Extension. Conclusion: Cladribine tablets treatment for 2years followed by 2years' placebo treatment produced durable clinical benefits similar to 4years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.