Cladribine is an immunosuppressive drug that produces a phenomenon of relatively selective lymphocyte killing (apoptosis) because of a resistance of the effects of adenosine deaminase. It was tested in MS patients and has a background in the treatment of lymphoid neoplasms and other autoimmune disorders.

The first-year results of a double-blind, placebo-controlled, cross-over study of intravenous cladribine in 50 patients with progressive MS, which was designed as a two-year study, were favourable. Neurologic scores and total lesion volumes on MRI were stable or improved in the patients receiving cladribine, but continued to deteriorate in patients on placebo. These favourable results could not be replicated in a recent phase III study in which 159 patients with progressive MS were randomised to receive cladribine in two different doses (0.7 or 2.1 mg/kg) or placebo. Patients were assessed monthly for 12 months with serial evaluation of disability scores and semiannual measurement of MRI. Although cladribine treatment had a remarkable effect in reducing the volume of gadolinium enhancement on MRI, a significant effect on disability could not be shown. The side-effect profile of this compound includes bone marrow suppression and increased susceptibility to viral infections (especially herpes zoster). Studies with oral cladribine are ongoing.

In the opinion of the Committee, therapy with cladribine has no proven clinical benefit. It must be considered investigational at this time because its use carries significant risk.