AAN 2011: Oral Cladribine Reduces Relapses in MS Patients Who Failed Injectable Therapies

Results from the CLARITY study show cladribine reduces the relapse rate in multiple sclerosis patients who have failed other disease-modifying therapies.

The oral drug cladribine reduces the relapse rate in multiple sclerosis patients who have failed other disease-modifying therapies, according to a study presented at the 63rd Annual Meeting of the American Academy of Neurology.

Cladribine reduced relapse rate among all patients by 41.5% when dosed at 3.5 mg/kg, and by 56.1% when dosed at 5.25 mg/kg, versus placebo. The effect on relapse rate was significantly better than placebo in patients intolerant of injectable therapies, but not in patients who had not responded to previous treatment.

“Many patients with relapsing-remitting multiple sclerosis are unable to tolerate treatment with current injectable disease-modifying drugs, or fail to achieve adequate control of symptoms or disease progression,” according to lead author Stuart Cook, MD, of the University of Medicine and Dentistry, New Jersey Medical School, Newark, NJ.

About one-third of the patients in the CLARITY study, a 96-week pivotal trial of cladribine, had received prior treatment with injectable therapies, including interferon beta and glatiramer acetate. Approximately half of those patients had failed treatment, defined as either suboptimal response (n=78) or intolerance (n=152) to previous injectable treatment. Cook performed a sub-group analysis on these patients to determine cladribine's efficacy in this clinical situation.

In addition to the dose-dependent improvement in relapse rate with cladribine, patients experienced reduction in brain gadolinium-enhancing MRI lesion activities of 91% and 94% for low and high doses respectively, 75% and 88% reduction in T2 lesions, and 77% and 87% reduction in combined lesions (all differences significant versus placebo at p<0.0001). Significant improvements were seen in both the injection-intolerant and the non-responder subgroups.

A significant delay in progression on the EDSS disability scale was seen for patients in the non-responder subgroup at the low cladribine dose, but not in non-responders at the higher dose or with either dose for those who were intolerant to previous therapies.

Cladribine was discontinued by 7 patients in the low-dose, 8 patients in the high-dose, and 2 patients in the placebo group. Lymphopenia was the predominant reason for discontinuation among those receiving active treatment. These discontinuations were in contrast to those seen with injectable therapies, Cook noted, which were primarily due to injection-site reactions and flu-like symptoms.

“These results support the potential use of cladribine in fulfilling an unmet medical need in relapsing-remitting multiple sclerosis,” Cook said.

The differential effect on relapse rate seen between the injection-intolerant and non-responder groups may be a reflection of the smaller patient numbers in the non-responder group. “It is also possible that this group included relatively treatment-resistant patients,” he said.

The study was funded by Merck Serono of Switzerland