This double-blinded multicentre, randomised, phase 3 study looked at the effects of oral cladribine on conversion to clinically definite MS in individuals presenting with a first clinical demyelinating event.



The active metabolite of cladribine, 2-chlorodeoxyadenosine triphosphate, exerts an apopotic effect on lymphocytes with relative sparing of other immune cells. The inclusion criteria included 616 patients presenting with a first clinical demyelinating event within 75 days before screening, who had at least two clinically silent lesions of at least 3mm on a T2-weighted brain MRI scan and an EDSS score of 5.0 or below. Eligible patients were assigned 1:1:1, to receive cladribine tablets at cumulative doses of 5.25 mg/kg or 3.5 mg/kg or placebo. The primary endpoint was time to conversion to clinically definite MS according to the Poser criteria. Overall the results demonstrated that cladribine was associated with a reduced risk compared to placebo on the time to conversion to clinically definite MS. There was no increase in the risk of adverse events with active treatment versus placebo other than lymphopenia, which was severe in 5% of patients in the higher treatment group and 2% of patients in the lower treatment group.



Therefore this study showed that patients with a first clinical demyelinating event suggestive of MS, treated with cladribine over two years, significantly delayed conversion to clinically definite MS and also significantly reduced MRI lesion counts compared to placebo. Further studies are needed to investigate the use of cladribine as an induction agent in MS.





Authors: Leist TP, Comi G

Source: Lancet Neurol. 2014 Feb 3. pii: S1474-4422(14)70005-5. doi: 10.1016/S1474-4422(14)70005-5. [Epub ahead of print]

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