Early onset of effect of treatment with cladribine tablets for relapsing-remitting multiple sclerosis in the 96-week, phase III, double-blind, placebo-controlled CLARITY study

BACKGROUND: Cladribine is activated specifically in lymphocyte sub-types resulting in targeted and sustained immunomodulation, whichprovides the rationale for use of cladribine tablets as a short-courseannual treatment in multiple sclerosis (MS). We investigated the timeof onset of treatment effect with cladribine tablets relative to placebo,in the CLARITY (CLAdRIbine tablets Treating multiple sclerosisorallY) study in patients with relapsing-remitting MS (RRMS). METHODS: Patients with RRMS (McDonald criteria; ExpandedDisability Status Scale [EDSS] score 0-5.5) were randomised 1:1:1 tocladribine tablets (cumulative dose of 5.25 or 3.5 mg/kg), or matchingplacebo. Cladribine tablets were given in short courses (once daily for4-5 days) in 4 or 2 consecutive months (28-day periods) in the first 48weeks, then 2 short courses at Weeks 48 and 52 (for both groups).Qualifying relapses were evaluated serially throughout the study,and MRI parameters (T1-Gd+, active T2, and combined unique [CU]lesions per patient per scan) were evaluated at 24, 48 and 96 weekspost-randomisation. RESULTS: The ITT population comprised 456, 433 and 437 patientsrandomised to 5.25 mg/kg, 3.5 mg/kg or placebo groups, respectively.Differences in qualifying relapse rate between active treatment groupsvs. placebo were apparent as early as 4 weeks post first treatmentcourse (5.25 and 3.5 mg/kg vs. placebo: 0.27 and 0.23 vs. 0.42, respec-tively). Statistically significant differences for all three MRI parameterswere also evident at the first assessment (mean number of lesions perpatient per scan in the 5.25 and 3.5 mg/kg vs. placebo groups at Week24: 0.07 and 0.07 vs. 0.97 for T1 Gd+ lesions, 0.33 and 0.45 vs. 1.59for active T2 lesions, and 0.38 and 0.49 vs. 1.91 for CU lesions,respectively). CONCLUSIONS: Treatment with cladribine tablets resulted in earlyonset of effect in clinical and MRI outcomes. Taken together withthe favourable tolerability and safety results observed in this study(reported elsewhere), these findings provide strong support forannual short-course treatment with cladribine tablets in patientswith MS