A 2-year, placebo-controlled, double-blind, crossover study was started in 1992 to evaluate cladribine, an immunosuppressive drug, in the treatment of chronic progressive multiple sclerosis. In the first year patients were given cladribine 0.10 mg/kg per day for 7 days as four monthly courses for a total of 2.8 mg/kg or placebo. During the second year patients treated with placebo during the first year were given i.v. infusions of 0.10 mg, 0.05 mg, and 0. Since there is no satisfactory treatment for chronic progressive MS, the use of cladribine was considered because of its relatively low toxicity and the long-lasting lymphopenia that it produces. Open-label feasibility studies were begun in 1990 with a small number of patients. The results in terms of both apparent benefit on neurological performance and lack of toxicity were favorable and encouraged us to proceed with a larger 2-yr placebo-controlled crossover study to further explore issues of safety and therapeutic effect. The first-year results of this study showed a positive effect (7). We now report observations from the entire 2 yr of this double-blind study and an additional 6-mo unblinded follow-up. tTo whom reprint requests should be addressed at: METHODS

We conducted an 18-month, placebo-controlled, double-blind study to evaluate cladribine in the treatment of 52 patients with relapsing-remitting multiple sclerosis. Patients received either placebo or cladribine 0.07 mg/kg/day by subcutaneous injection for 5 consecutive days as six monthly courses for a total cumulative dose of 2.1 mg/kg. Analysis of results revealed a statistically significant favorable effect of cladribine on the joint frequency and severity of relapses and magnetic resonance imaging (MRI) findings. MRI-enhancing lesions were completely suppressed in the cladribine patients by the sixth month of treatment. Mild segmental herpes zoster occurred in two cladribine-treated patients and one patient receiving placebo. Otherwise, there were no side effects or adverse events. We conclude that cladribine shows promise as a treatment for relapsing-remitting multiple sclerosis.

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We used a flow cytometry assay to measure proliferation and cytokine production of self-antigenspecific T cells in individual patients during the clinical course of multiple sclerosis (MS). Myelinassociated oligodendrocytic basic protein (MOBP) was selected for proof of principles in the assay, along with myelin basic protein (MBP) to assess specific activated T cells in 10 MS patients over an 18-month period, in parallel with brain magnetic resonance imaging (MRI) scans and clinical rating scale. A positive correlation occurred between antigen-specific T cell proliferation and interferon-γ production with clinical relapses and MRI lesion activity that was absent when the same patients were in remission.

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