Cladribine is a drug used in chemotherapy. It has been effective in the treatment of certain leukaemias and lymphomas. It is likely to be of benefit in MS by suppressing the immune system. It was tried in MS because it is relatively less toxic than some of the other anti-cancer agents.
There have been studies of cladribine in MS in the literature since 1996, however, it has now been tested in the oral form and found to be effective. In January 2005, a large pharmaceutical company announced that it was beginning large scale trials of an oral formulation of cladribine.
This study has now been completed although at this time, the results have not been peer reviewed or published. This study, the CLARITY study, was a 96 week RCT enrolling 1,326 patients with relapsing-remitting MS. A low dose and high dose of cladribine were tested against placebo.
The cladribine tablets were taken in two or four treatment 4-5 day courses in the first year, so patients took cladribine tablets for only 8 to 20 days in the year. In the second year, all participants took two treatment courses.
The relapse rate in the placebo group was 0.33 per year on average; this fell to 0.14 per year in the low dose group, a 58% reduction (p<0.001) , and 0.15 in the high dose group, a 55% reduction (p<0.001).
The drug was well tolerated with more patients in the treatment groups finishing the study than those in the placebo groups, and relatively mild side effects according to data released by the drug company.
Longer term studies are under way looking at longer term safety, but as a chemotherapy agent, there are likely to be some downsides to long term treatment, especially related to bone marrow suppression and infections.
Side-effects of cladribine are relatively mild considering the class of drug. Bone marrow suppression, decreased platelet count and decreased white cell count have been recorded. Shingles may also occur, as with other immunosuppressant therapies.
The good news with this study is that the lower dose worked so well, at least as well as the higher dose, and that people tolerated the drug so well and stayed in the study.
This compares very favourably to the interferon studies where there was a very high drop out rate. The other really positive aspect is that the drug is taken orally, and only for a few days each year.
It has the potential to really make a difference to the lives of people with MS if it proves in the longer term to be safe, and if it actually makes a difference to disease progression. The drug company is submitting cladribine for approval in mid-2009 in the and Europe. It has been granted fast-track status by the FDA.