Cladribine is an antineoplastic agent licensed previously for the treatment of hairy cell leukaemia (Leustat, Litak) and B-cell chronic lymphocytic leukaemia (Leustat). The mechanism by which the drug exerts its effects in MS is not fully understood but it is thought that its predominant effect on B and T lymphocytes interrupts the cascade of immune events central to the disease.
Improvements in relapse rates
In the study (n=1,326) patients with relapsing-remitting MS were randomised to receive a cumulative dose of cladribine 3.5mg/kg (n=433) or 5.25mg/kg (n=456), or placebo (n=437) over 96 weeks in two treatment courses. Treatment courses were given at weeks 1 and 5 of each year with patients in the higher dose group given additional treatment at weeks 9 and 13 of the first year.
Patients in the cladribine 3.5mg/kg group showed significant improvements in the annualised relapse rate, with a relative reduction of 57.6% compared with those in the placebo group. In addition, cladribine 3.5mg/kg was associated with significant improvements in the proportion of patients relapse-free over 96 weeks (79.7% vs 60.9%), proportion of patients free of sustained disability over 96 weeks, and time to 3-month Expanded Disability Status Scale (EDSS) progression (13.6 vs 10.8 months) compared with those in the placebo group.
Higher cumulative doses were not found to add any clinically meaningful benefit but were associated with a higher incidence in ≥grade 3 lymphopenia (44.9% in the 5.25mg/kg group vs 25.6% in the 3.5mg/kg group).
Findings from the study showed that the magnitude of effect in reducing the frequency of relapse and slowing disability progression in patients receiving cladribine 3.5mg/kg was maintained in years 3 and 4.
The most commonly reported adverse effects in clinical studies with cladribine were lymphopenia and herpes zoster. Lymphocyte counts should be monitored before initiating treatment and two and six months after the start of treatment in each treatment year. The lymphocyte count must be normal before starting treatment in year 1 and ≥800 cells/mm3 in year 2.
Treatment administration simplified
Commenting on the launch of Mavenclad, Gavin Giovannoni, Professor of Neurology at Barts and the London School of Medicine and Dentistry, Queen Mary University of London said, "This is an exciting moment and one that will change the way we treat MS". He added, "Mavenclad is a selective immune reconstitution therapy (SIRT) which simplifies treatment administration, by giving patients just two short annual courses of tablets in four years. Patients can benefit from the treatment over a longer period of time without having to continually take medication and without the need for frequent monitoring."