Reduced brain atrophy rates are associated with lower risk of disability progression in patients with relapsing multiple sclerosis treated with cladribine tablets

Abstract

Background:Neuroimaging studies have used magnetic resonance imaging-derived methods to assess brain volume loss in multiple sclerosis (MS) as a reliable measure of diffuse tissue damage.Methods:In the CLARITY study (ClinicalTrials.gov NCT00213135), the effect of 2 years’ treatment with cladribine tablets on annualized percentage brain volume change (PBVC/y) was evaluated in patients with relapsing MS (RMS).Results:Compared with placebo (–0.70% ± 0.79), PBVC/y was reduced in patients treated with cladribine tablets 3.5 mg/kg (–0.56% ± 0.68, p = 0.010) and 5.25 mg/kg (–0.57% ± 0.72, p = 0.019). After adjusting for treatment group, PBVC/y showed a significant correlation with the cumulative probability of disability progression (HR = 0.67, 95% CI = 0.571, 0.787; p < 0.001), with patients with lower PBVC/y showing the highest probability of remaining free from disability progression at 2 years and vice versa.Conclusions:Cladribine tablets given annually for 2 years in short-duration courses in patients with RMS in the CLARITY study significantly reduced brain atrophy in comparison with placebo treatment, with residual rates in treated patients being close to the physiological rates.

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options

“…Cladribine, an antiproliferative agent that takes effect by interfering with DNA synthesis, has shown significant effects in terms of relapse rate and disability progression [160,161]. Data from CLARITY study suggested that at 18 months, patients treated with cladribine had 20%reduction in brain atrophy compared with patients receiving placebo [162]. However, further studies are needed, in order to cladribine's effect on brain atrophy rates, be fully elucidated [161,163,164].…”

Effects of disease modifying therapies on brain and grey matter atrophy in relapsing remitting multiple sclerosis

“…An exploratory analysis on the cladribine tablets treating multiple sclerosis orally (CLARITY) study (phase-3, double-blind, placebo-controlled, multicenter trial in patients with RMS assessing the effects of cladribine tablets given annually over 2 years) [117] disclosed that cladribine significantly reduced brain atrophy in comparison with placebo treatment, with residual rates in treated patients being close to the physiological rates [118]. Indeed, compared with placebo (−0.70% ± 0.79), the annualized percentage brain volume change (PBVC/ y) was reduced in patients treated with cladribine tablets 3.5 mg/kg (−0.56% ± 0.68, p = 0.010) and 5.25 mg/kg (−0.57% ± 0.72, p = 0.019).…”

Cladribine: mechanisms and mysteries in multiple sclerosis

“…Cladribine treatment was associated with an increase in the proportion of participants who remained free from Gd-enhancing lesions and new T2 lesions at the end of the 96-week study period 24. There was also a statistically significant reduction in annual brain volume loss in the cladribine treatment groups compared with placebo 25. The positive clinical effects were further underpinned by positive Quality of life data also indicated significant improvement in one out of the two metrics used (EQ-5D) in the cladribine versus placebo groups 26.…”