Epub: Comi et al. MRI outcomes with cladribine tablets for multiple sclerosis in the CLARITY study. J Neurol. 2012.
Objectives: We herein provide a comprehensive assessment of magnetic resonance imaging (MRI) outcomes from CLARITY, a 96-week, double-blind study demonstrating significant clinical and MRI improvements in patients with relapsing-remitting multiple sclerosis (RRMS) treated with cladribine tablets.
Methods: Patients with RRMS were randomized 1:1:1 to annual short-course therapy with cladribine tablets cumulative dose 3.5 or 5.25 mg/kg or placebo. MRI endpoints included mean number of T1 gadolinium-enhancing (Gd+), active T2 and combined unique (CU) lesions/patient/scan. MRI-measured disease activity was significantly reduced in both cladribine tablets groups versus placebo.
Results: The proportion of patients with no active lesions at study end was: T1 Gd+ lesions: 86.8 and 91.0 versus 48.3 % (p < 0.001); active T2 lesions: 61.7 and 62.5 versus 28.4 % (p < 0.001); CU lesions: 59.6 and 60.7 versus 26.1 % (p < 0.001). Clinically meaningful and significant reductions in active lesion counts and increases in proportions of active lesion-free patients were achieved consistently in cladribine tablet groups when data were stratified by baseline disease characteristics. For example, the percentage of patients who remained lesion-free over the study was significantly greater in cladribine tablet groups than in the placebo group for all lesion types regardless of relapse category at baseline (p < 0.001 for all analyses of patients with ≤1 or 2 relapses; p ≤ 0.022 for analyses of patients with ≥3 relapses).
Conclusion: MRI-measured disease activity was greatly reduced by both doses of cladribine tablets, with consistent effect across clinically relevant patient populations. These findings add to our scientific understanding of the neurological impact of this therapeutic modality in patients with RRMS.
Yet more evidence that oral cladribine was active in treating RRMS. This study looking at MRI lesions supports the clinical observations already published, that cladribine can . Despite the promising efficacy data observed in the cladribine tablets clinical trial program, because of concerns made by the regulators, Merck-Serono made the decision to withdraw the agent from the regulatory approval process.
Surely it is time to re-investigate generic cladribine or the other oral agents that work via this mechanisms, which will clearly work as well as the new DMTs and would be unlikely to have any worse side-effects than most new DMT.
CoI: Prof G was a co-author and PI on the CLARITY study