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NICE guidance - cladribine for treating relapsing–remitting multiple sclerosis

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Cladribine is recommended as an option for treating highly active multiple sclerosis in adults, only if the person has (1):Cladribine is recommended as an option for treating highly active multiple sclerosis in adults, only if the person has (1):

  • rapidly evolving severe relapsing - remitting multiple sclerosis, that is with at least:
    • 2 relapses in the previous year and
    • 1 T1 gadolinium-enhancing lesion at baseline MRI or a significant increase in T2-lesion load compared with a previous MRI, or
  • relapsing - remitting multiple sclerosis that has responded inadequately to treatment with disease-modifying therapy, defined as 1 relapse in the previous year and MRI
    evidence of disease activity

Cladribine is a deoxyadenosine analogue prodrug that preferentially depletes lymphocytes, key cells underlying multiple sclerosis (MS) pathogenesis (2):

  • cladribine has a prolonged intracellular residence time (due to its resistance to the purine-degrading enzyme, adenosine deaminase) and is phosphorylated to its active triphosphate moiety (CdATP) by intracellular deoxycytidine kinase (DCK)
    • process occurs especially well in lymphocytes, due to their high DCK levels and low levels of 5′-nucleotidase (5′-NTase; an enzyme that dephosphorylates and inactivates CdATP)

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