Analysis of relapse rates and relapse-free patients in the CLARITY and CLARITY extension studies

BACKGROUND: In CLARITY, giving cladribine tablets (CT) annually for 2 years, significantly reduced relapse rates and disability progression vs placebo (PBO) in patients with relapsing multiple sclerosis. OBJECTIVE: To assess the efficacy of 2-years’ additional treatment with CT or PBO in the CLARITY Extension (EXT) study. METHODS: In CLARITY-EXT, patients given PBO in CLARITY received CT3.5mg/kg bodyweight (CT3.5); those given CT3.5 or CT5.25mg/kg (CT5.25) in CLARITY were re-randomised to CT3.5 or PBO. Annualised relapse rates (ARR) and proportions of patients qualifying relapse free were compared at different times (i.e. CLARITY and CLARITY-EXT) within the following groups : patients treated with CT3.5 in CLARITY/PBO in CLARITY-EXT (n=98); CT3.5 in CLARITY/CT3.5 in CLARITY-EXT (n=186); CT5.25 in CLARITY/CT3.5 in CLARITY-EXT (n=186); PBO in CLARITY/CT3.5 in CLARITY-EXT (n=244). RESULTS: No significant differences in ARR were seen between CLARITY and CLARITY-EXT except in patients who received PBO in CLARITY and CT3.5 in CLARITY-EXT (0.26 vs 0.10, p<0.0001). In CLARITY-EXT, >70% of patients qualified relapse-free in each group, with no significant differences between CLARITY and CLARITY-EXT except in patients treated with PBO in CLARITY and CT3.5 in CLARITY-EXT (58.0% vs 79.6%, p<0.0001). CONCLUSIONS: For patients who received PBO in CLARITY, switching to CT3.5 in CLARITY-EXT significantly reduced ARR and increased the proportion of relapse-free patients. CT also produced durable clinical benefits : patients who received CT in CLARITY and PBO in CLARITY-EXT maintained low relapse rates throughout. Patients who received CT in CLARITY and CT in CLARITY-EXT showed no additional benefit vs treatment with CT in CLARITY only.