Durability of no evidence of disease activity-3 (NEDA-3) in patients receiving cladribine tablets: The CLARITY extension study

Background: No evidence of disease activity (NEDA-3) is a patient-centric outcome increasingly used as the goal of multiple sclerosis treatment. Objective: Determine treatment durability of cladribine tablets beyond 2 years considering the variable bridging interval of 0.1–116.0 weeks between CLARITY and CLARITY Extension. Methods: Between CLARITY and CLARITY Extension, patients transitioned from cladribine tablets 3.5 mg/kg to placebo (CP3.5 group, n = 98) or continued further treatment with cladribine tablets 3.5 mg/kg (CC7.0 group, n = 186). Treatment assignment was randomized and blinded in both CLARITY and CLARITY Extension. Results: The 2-year NEDA-3 in CLARITY Extension (encompassing both years of CLARITY Extension) was 29.6% in the CP3.5 group and 32.8% in the CC7.0 group. There was no evidence that treatment effect differed with varying bridging intervals. For patients in the CP3.5 group with a bridging interval of ⩽48 weeks, 1 year NEDA-3 (the first year of CLARITY Extension) was 44.4% (28/63) compared with 31.4% (11/35) in patients with a bridging interval of >48 weeks. Conclusion: Treatment with cladribine tablets in CLARITY, followed by either placebo or cladribine tablets in CLARITY Extension, produced sustained benefits for NEDA-3 and its constituent elements for a follow up period up to 6 years from CLARITY baseline.

Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: The CLARITY and CLARITY Extension studies

Background: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study of patients with relapsing-remitting multiple sclerosis, treatment with cladribine tablets 3.5 mg/kg (CladT) significantly reduced the annualised relapse rate (ARR) versus placebo; this effect was sustained in CLARITY Extension, without further treatment. Objective: To assess the frequency and severity of relapses in patients treated with CladT versus placebo in CLARITY over 2 years and evaluate the durability of effect in patients who received no further treatment for 2 years in CLARITY Extension. Methods: In this post hoc analysis, ARRs were calculated for qualifying and all relapses, and qualifying and all severe relapses (i.e. requiring steroid treatment or leading to hospitalisation) in patients treated with CladT ( n = 433) and placebo ( n = 437) in CLARITY, and those from the CladT group who received placebo in CLARITY Extension ( n = 98). Results: At Month 6, Year 1 and Year 2, patients receiving CladT had a significantly lower risk of qualifying or all relapses (all p < 0.0001), and qualifying or all severe relapses (all p < 0.005), compared with placebo. This effect was sustained in CLARITY Extension without further treatment. Conclusion: The results show durable efficacy of cladribine tablets 3.5 mg/kg for reducing frequency and severity of relapses in patients with relapsing-remitting multiple sclerosis. CLARITY: NCT00213135; CLARITY Extension: NCT00641537