NICE guidance - cladribine for treating relapsing–remitting multiple sclerosis

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)

Reference:

• NICE (December 2019). Cladribine for treating relapsing - remitting multiple sclerosis
• Deeks E. Cladribine Tablets: A Review in Relapsing MS.CNS Drugs. 2018; 32(8): 785-796