NICE recommends cladribine for highly active MS
In a final appraisal determination, NICE has recommended cladribine (Mavenclad) as an option for the treatment of highly active multiple sclerosis (MS) in adults. NICE recommends treatment with cladribine only if the patient has rapidly evolving severe relapsing-remitting MS (ie at least two relapses in the previous year and at least one T1 gadolinium-enhancing lesion at baseline MRI) or relapsing-remitting MS that has responded inadequately to treatment with disease-modifying therapy (defined as one relapse in the previous year and MRI evidence of disease activity).
Up until now, the main treatment options for highly active relapsing-remitting MS have been the biological therapies alemtuzumab, daclizumab and natalizumab, which are administered by intravenous infusion or subcutaneous injection, or the oral immunosuppressant fingolimod. NICE points out that, although there is not enough evidence to determine whether cladribine is more or less effective than these other treatments, it is a cost-effective option and needs less frequent dosing and monitoring.
The oral formulation of cladribine was licensed for the treatment of adult patients with highly active relapsing MS, as defined by clinical or imaging features, in August 2017. Cladribine has also been available as an intravenous infusion for the treatment of leukaemia since the 1990s (marketed as Leustat). It is a nucleoside analogue of deoxyadenosine, which is converted to its active form 2-chlorodeoxyadenosine triphosphate (Cd-ATP) within cells, inducing apoptosis (programmed cell death). This conversion is particularly efficient in lymphocytes, leading to the selective depletion on T and B cells and an immunosuppressant action.
The efficacy of cladribine was demonstrated in the phase 3 CLARITY trial, in which cladribine reduced the annualised relapse rate by 58% compared with placebo in patients with relapsing-remitting MS. The most common adverse effect is lymphopenia, and lymphocyte count must be normal before initiating cladribine treatment; other common side-effects include neutropenia, oral herpes and rash.
Cladribine is available as 10mg tablets, and the recommended cumulative dose is 3.5mg/kg body weight over two years, taken as one treatment course of 1.75mg/kg per year. Following completion of the two treatment courses, no further cladribine treatment is required in years three and four; treatment beyond year four has not been studied.
The list price of cladribine is £2047 per 10mg tablet, making the cost of a year’s treatment for a 70–80kg adult approximately £28,660.