Cladribine

Because autoimmune mechanisms have been implicated in the etiology of multiple sclerosis, antilymphocytic agents that were originally developed to treat leukemia and other related conditions theoretically could be effective in the treatment of multiple sclerosis. Cladribine is a highly specific antilymphocyte agent with relatively low toxicity. Sipe and colleagues performed a randomized, double-blind trial of cladribine in patients with chronic progressive multiple sclerosis.

The study included 51 patients who had confirmed chronic progressive multiple sclerosis of at least two years' duration and were established patients of a neurology clinic. They were matched into 24 pairs by age, sex and severity of disease. Three patients were lost to follow-up during the study One member of each pair was randomly assigned to receive cladribine through a surgically implanted catheter, and the other member received placebo.

The study was originally designed as a two-year crossover trial, but the study was concluded after one year of treatment because significant results were apparent by this time. During the trial, other treatments were continued as needed to control symptoms of multiple sclerosis. Patients were monitored by magnetic resonance imaging (MRI), evaluation of cerebrospinal fluid (CSF) and blood chemistry, and clinical evaluation. The primary end-point was clinical assessment by a neurologist who was blinded to the treatment status of each patient.

After one year, patients treated with cladribine showed stable or improved status in average neurologic scores, demyelinated volumes on MRI and concentrations of oligoclonal bands in CSF. These parameters continued to deteriorate in patients who received placebo. The differences in parameters between the treatment group and the placebo group were statistically significant. Several patients showed signs of bone marrow suppression, but this problem was only clinically significant in one patient. Herpes zoster developed in two patients in the cladribine group, and a serious hepatitis B infection occurred in another patient. These infections did not appear to be related to the study treatment.

The authors conclude that cladribine is a potentially useful agent for the treatment of chronic progressive multiple sclerosis. They plan future trials using a subcutaneous preparation of this drug. (Lancet, July 2,1994, vol. 344, p. 9.)

COPYRIGHT 1995 American Academy of Family Physicians
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