Cladribine and progressive MS - Clinical and MRI outcomes of a multicentercontrolled trial

Objective: To evaluate the safety and efficacy of two doses of cladribine i n patients with progressive MS. Background: Treatment of progressive MS pat ients with cladribine in a previous single-center, placebo-controlled clini cal trial was associated with disease stabilization. Methods: In the curren t study, 159 patients with a median baseline Kurtzke's Expanded Disability Status Scale (EDSS) score of 6.0 were randomly assigned to receive placebo or cladribine 0.07 mg/kg/day for 5 consecutive days every 4 weeks for eithe r two or six cycles (total dose, 0.7 mg/kg or 2.1 mg/kg, respectively), fol lowed by placebo, for a total of eight cycles. Thirty percent had primary p rogressive MS (PPMS) and 70% had secondary progressive MS (SPMS). EDSS and Scripps Neurologic Rating Scale (SNRS) scores were assessed bimonthly and M RI was performed every 6 months. The primary outcome measure was disability (mean change in EDSS). Results: Mean changes in disability did not differ among the groups at the end of the 12-month double-blind phase. Both cladri bine treatments were superior to placebo for the proportion of patients hav ing gadolinium-enhanced T1 lesions and for the mean volume and number of su ch lesions (p less than or equal to 0.003). Differences were statistically significant at the B-month evaluation time, with greater than or equal to 9 0% reduction in volume and number of enhanced T1 lesions, which was maintai ned through final evaluation. This effect segregated largely with the SPMS group. The T2 burden of disease showed a modest improvement in cladribine-t reated patients and worsened in placebo-treated patients. Most adverse even ts were mild or moderate in severity and not treatment limiting. Conclusion : No significant treatment effects were found for cladribine in terms of ch anges in EDSS or SNRS scores. Both doses of cladribine produced and sustain ed significant reductions in the presence, number, and volume of gadolinium -enhanced T1 brain lesions on MRI, and cladribine 2.1 mg/kg reduced the acc umulation of T2 lesion load. Cladribine at doses up to 2.1 mg/kg was genera lly safe and well tolerated.