This chapter reviews the mechanism of action of cladribine, summarizes data from clinical trials in patients with multiple sclerosis (MS), and provides guidance on the management of these patients in clinical practice. The study of parenteral cladribine showed encouraging results, which lead to the development of an oral tablet formulation. Cladribine is rapidly absorbed with Cmax within 30- 50 minutes after oral administration. CLARITY, a 96-week, placebo-controlled Phase 3 study of cladribine tablets as an annual short-course oral monotherapy in RRMS, was recently completed and the principal results published. Benefit of doses of cladribine over placebo was demonstrated for a variety of clinical and imaging end-points. The most common adverse events in the patients were lymphopenia, headache, nasopharyngitis, and upper respiratory tract infections (URTI). The outcomes observed during the CLARITY study were associated with a reduced consumption of health care resources and a decreased need for medical and societal support.

The atypical characteristics of primary progressive multiple sclerosis (PPMS) have presented problems in the recruitment to and design of therapeutic trials. The problem areas in the implementation of therapeutic trials are: diagnostic criteria, sample size calculations, and choice of outcome measures. Although there is no definitively proven disease-modifying treatment available for PPMS, several randomized controlled trials have now been specifically designed for this group. The clinical trials in PPMS are based on glatiramer acetate and rituximab. The planned clinical trials in PPMS are based on fingolimod (FTY720) and cladribine. The smaller trials in PPMS are based on Interferon beta-1a, Interferon beta-1b, mitoxantrone and riluzole. A retrospective open-label study of intravenous cyclophosphamide and methylprednisolone in progressive MS included 128 patients with PPMS. PPMS may be the ideal model to investigate disease progression and neuronal protection, and is becoming an important focus for treatment trials in these areas.