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Cladribine Is Safe Overall in Patients With Multiple Sclerosis: Presented at ENS

By Judith Moser, MD

MILAN, Italy -- June 24, 2009 -- According to a safety analysis of a study presented here at the 19th Meeting of the European Neurological Society (ENS), the incidence of treatment-emergent adverse events in the trial was comparable between 2 doses of cladribine and placebo in patients with multiple sclerosis (MS), with exceptions related to the mechanism of action of cladribine.

In the 96-week phase 3, randomised, double-blind, placebo-controlled Cladribine Tablets Treating MS Orally (CLARITY) trial, cladribine tablets demonstrated significant efficacy in the treatment of patients with relapsing-remitting MS.

Vissia Viglietta, MD, Merck Serono, Inc., Rockland, Massachusetts, presented the safety results of the study at a poster presentation on June 22.

The trial assessed 2 dosing regimens of the immunomodulatory drug and compared them with placebo. A total of 1,326 patients were randomised to either cladribine 5.25 mg/kg total dose, cladribine 3.5 mg/kg total dose, or placebo.

As expected based on the mechanism of action of cladribine, lymphopenia occurred more frequently with active treatment. The association was dose related; patients in the highest-dose group showed the highest incidence (31.5% vs 21.6% and 1.8% in the 3.5-mg/kg and placebo groups, respectively).

"This finding was not associated with any clinical outcomes," Dr. Viglietta emphasised. "Furthermore, the vast majority of patients recovered quickly during the 96-week period."

Infections/infestations occurred with similar incidence across treatment groups (48.9%, 47.7%, and 42.5% with cladribine 5.25 mg/kg, cladribine 3.5 mg/kg, and placebo, respectively), suggesting that first-line immune defence mechanisms remained adequate.

In almost all cases in each group, infections were considered mild or moderate by the investigators.

"Three isolated solid malignancies occurred in the 3.5-mg/kg group," Dr. Viglietta reported. "They were unrelated to the mechanism of action of cladribine." One choriocarcinoma was noted in the highest-dosage group approximately 9 months after the completion of the study.

In the 5.25-mg/kg, 3.5-mg/kg, and placebo groups, 7.9%, 3.5%, and 2.1% of patients discontinued treatment because of adverse events (AEs). Lymphopenia was the reason for discontinuation in 2.0%, 0.5%, and 0%.

Apart from blood and lymphatic system disorders, AEs leading to treatment discontinuation were comparable across the treatment groups. In the same group order, 9.0%, 8.4%, and 6.4% of patients experienced serious AEs.

"We are acquiring more safety data with the 4-year extension trial," Dr. Viglietta concluded. At the same time, a safety registry is being established. "Every patient who has been treated with cladribine even once will be followed for a total of 8 years."

Funding for this study was provided by Merck Serono S.A.

[Presentation title: Safety of Cladribine Tablets in the Treatment of Relapsing-Remitting Multiple Sclerosis: Results From the CLARITY Study, a 96-Week, Phase III, Double-Blind, Placebo-Controlled Trial. Abstract P360]

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