Cladribine

Cladribine (Mavenclad) is a drug for people with active relapsing remitting MS taken orally over two years.

Cladribine (Mavenclad) received marketing authority in 2017 for use in “very active relapsing remitting MS”.  This is usually defined as 2 or more relapses in 1 year, but working definitions change from country to country.  

The drug was initially developed as a treatment for a form of leukaemia, in injectable form.  It appears to work by targeting two types of white blood cell (B and T lymphocytes), destroying them temporarily.  The immune system then rebuilds these cells, with the theory being that they will no longer target the body’s own myelin sheath (the fatty covering of nerves that is damaged in MS).  It doesn’t appear to suppress the overall immune system, so infections can still be fought, and it also doesn’t appear to damage cells other than the white blood cells, limiting side effects.

Cladribine was initially put forward for approval in 2010, but withdrawn due to concerns over increased numbers of cancers in the treatment group, versus those in the placebo group of the trial (those who did not receive the active drug).

When this was researched further and compared with other trials however, it was concluded that the relative increased cancer risk in the Cladribine group had been due to an actual reduced incidence in the placebo group compared with the general population – thereby appearing to make the figures appear worse in the treatment group. It is now felt that Cladribine does not increase the individual’s risk of cancer.

Treatment

In treating MS it is given as a tablet, with 2 treatment courses over 2 years.  Each treatment course consists of 2 treatment weeks, which are one month apart at the beginning of each treatment year.

 A treatment week consists of 4 or 5 days of taking one or two, 10mg tablets orally (depending on the patient’s weight), with or without food, daily. After the second dose in year two of treatment, individuals are observed for an additional 2 years.

It is unknown yet whether patients may require further treatment in subsequent years, but those in the original study haven’t required further treatment to date.

Evidence

Evidence for Cladribine in MS comes from the CLARITY trial.  It was a 2-year, phase III study of more than 1,300 people comparing 2 doses of cladribine against placebo. Compared to placebo, there was a reduction in relapse rate of 58%.  Later analyses of the study results also found that brain volume loss was reduced and numbers of participants with no evidence of disease activity (NEDA) were increased in those taking Cladribine.​  The chance of disability progression was reduced by around 30%.

Pregnancy and Breastfeeding

Cladribine should not be used by men or women while trying for a family, or in pregnancy. 

In men it can affect sperm production and quality for up to 6 months after treatment, and in women it could seriously harm the developing baby. Both men and women are advised to avoid pregnancy for 6 months following their most recent dose of Cladribine. Breastfeeding is not currently recommended.

Side Effects:

Common side effects (affecting more than 1 person in 100):

  •  decrease in white blood cells (lymphopenia)

  •  herpes virus infection (shingles or cold sores)

  •  rash

  •  hair loss

Before starting treatment, tests are performed to check for tuberculosis, HIV and hepatitis.

Conclusion

In summary, the evidence would suggest that Cladribine is effective, well tolerated and safe.  As with all the modern MS drugs, the longer-term effects are not fully understood, but at least the results show less serious potential side effects than some of the similarly effective drugs (such as Alemtuzumab and Natalizumab), in the medium term.  


Reference:

DOI: 10.1056/NEJMoa0902533

Page last updated 16 May 2019 

Medication