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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