Clinical outcomes of short-course oral treatment with cladribine tablets for relapsing-remitting multiple sclerosis (RRMS) in the 96-week, phase III, double-blind, placebo-controlled CLARITY study

PURPOSE: To assess the clinical efficacy of two short-course regimens of cladribine tablets compared with placebo over 96 weeks in patients with RRMS in the CLARITY (CLAdRIbine tablets Treating multiple sclerosis orallY) phase III study. METHOD: Patients with RRMS (McDonald criteria, Expanded Disability Status Scale [EDSS] score 0–5.5) were randomised 1:1:1 to cladribine tablets (cumulative dose 5.25 or 3.5 mg/kg) or matching placebo. Treatments were given in short courses (once daily for 4–5 days) in 4 or 2 consecutive months (28-day periods) in the first 48 weeks, then 2 short courses at Weeks 48 and 52 (for both groups). The primary efficacy endpoint was qualifying relapse rate over 96 weeks. RESULTS: Baseline characteristics of the cladribine 5.25 or 3.5 mg/kg and placebo groups (ITT n = 456, 433 and 437 patients, respectively) were well balanced (overall: 68% female, mean age 38.6 years and mean EDSS 2.9). Treatment with cladribine tablets resulted in significantly lower annualised qualifying relapse rates over 96 weeks (relative reduction vs. placebo: 57.6% with 5.25 mg/kg and 54.5% with 3.5 mg/kg cladribine tablets, all p < 0.001) and a greater proportion of relapse-free patients (79% with 5.25 mg/kg and 80% with 3.5 mg/kg groups vs. 61% in the placebo group, all p < 0.001). This was accompanied by a statistically significant 31% and 33% relative reduction in the risk of 3-month sustained disability progression over 96 weeks in the 5.25 and 3.5 mg/kg groups vs. placebo, respectively. CONCLUSION: Short-course treatment with cladribine tablets resulted in significant improvements relative to placebo in clinical outcomes. When taken together with favourable MRI outcomes and safety/tolerability data, both reported elsewhere, the results provide evidence for the use of cladribine tablets in the treatment of RRMS