MRI 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 evaluate the effects of two short-course regimens of cladribine tablets vs. placebo on MRI parameters in patients with RRMS treated in the CLARITY (CLAdRIbine tablets Treating multiple sclerosis orallY) study. METHODS: Patients with RRMS (McDonald criteria, Expanded Disability Status Scale [EDSS] score 0-5.5) were randomised 1:1:1 to cladribine tablets (cumulative dose of 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 (both groups). Prespecified, hierarchically arranged, secondary MRI endpoints over 96 weeks included mean number of T1 Gd+, active T2 and combined unique (CU) lesions/patient/scan. RESULTS: Cladribine 5.25 or 3.5 mg/kg and placebo groups (ITT n = 456, 433 and 437 patients, respectively) were well balanced at baseline in demographics and other characteristics, including number of T1 Gd+ lesions, T2 lesion volume and T1 hypointense lesion number. Disease activity on MRI assessment over 96 weeks was significantly reduced in cladribine 5.25 or 3.5 mg/kg groups vs. placebo, with relative reductions of 87.9% and 85.7% for T1 Gd+ lesions, 76.9% and 73.4% for active T2 lesions, and 77.9% and 74.4% for CU lesions (all p < 0.001 vs. placebo). There was also a significantly greater median change from baseline in T2 lesion volume (-1010.75 and -583.00 vs. -227.00mL in cladribine 5.25 and 3.5 mg/kg groups vs. placebo, respectively, all p < 0.001). Effects were evident from the first assessment point at 24 weeks. CONCLUSIONS: MRI evidence of disease activity was greatly reduced by both cladribine tablet treatment regimens. These findings were accompanied by significant improvements in clinical outcomes, and an acceptable risk-benefit profile, as reported elsewhere, and suggest that this drug offers benefits to patients with RRMS.