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| |  Cladribine Safe and Tolerable, Improves Outcomes in Patients With Relapsing-Remitting MS: Presented at ECTRIMS By Chris Berrie DÜSSELDORF, Germany -- September 16, 2009 -- Cladribine significantly improves a range of clinical and magnetic resonance imaging (MRI) outcomes while maintaining safety and tolerability in patients with definite multiple sclerosis (MS), researchers noted here at the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Gavin Giovannoni, MD, PhD, Neuroimmunology Unit, Neuroscience Centre, Institute of Cell and Molecular Science, Barts and the London NHS Trust, London, United Kingdom, presented the results of the multicentre, randomised, double-blind, placebo-controlled Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study on September 10 and 11. The study evaluated the use of oral cladribine for patients with relapsing-remitting MS (McDonald criteria), who had at least 1 relapse in the prior 48 weeks. In all, 1,326 patients were randomised to placebo (n = 437) or oral cladribine at either 3.5 mg/kg (n = 433) or 5.25 mg/kg (n = 456) for 96 weeks. The low-dose group received active treatment starting on day 1 and week 5, and then again at weeks 48 and 52. The high-dose group received the same, with further treatment added on weeks 9 and 13. Patient baseline characteristics were comparable across all groups. The primary efficacy endpoint was the rate of qualifying relapses at 96 weeks. Secondary endpoints included the proportion of relapse-free patients, the time to sustained disability progression, time to first relapse, and the proportion of patients receiving rescue therapy with interferon (IFN) beta-1a. Significant reductions were seen in both the low- and high-dose cladribine groups over placebo for an annualised relapse rate at 96 weeks (0.14/0.15 vs 0.33; P < .001 for both). Of the patients in the low- and high-dose cladribine groups, 79.7% and 78.9% were relapse-free compared with 60.9% of placebo patients (P < .001 for both). Time to first relapse was 13.4 months in the low-dose group, 13.3 months in the high-dose group, and 4.6 months in the placebo group (P < .001). The risk of 3-month sustained disability progression was also significantly reduced. The proportion of patients receiving rescue therapy with IFN beta-1a was 6.2% for patients receiving placebo versus 2.5%/2.0% for patients receiving high-dose/low-dose cladribine. Magnetic resonance imaging endpoints at 96 weeks showed reduction in T1 gadolinium-enhancing (Gd+) lesions for patients receiving both cladribine doses versus placebo (P < .001 for both), as well as reduction in active T2 lesions (P < .001 for both), and reduction in combined unique (CU) lesions (P < .001 for both). These improvements were all apparent and significant at the first MRI assessment of 24 weeks, and continued as such throughout the study. The proportion of lesion-free patients over 96 weeks was significantly increased for both cladribine treatments versus placebo for T1 Gd+ lesions, active T2 lesions, and CU lesions, (P < .001 for all). In the safety analysis, the overall incidences of adverse events were comparable across the 3 treatment groups, with some exceptions relating to the mechanism of action of cladribine. Lymphopenia was more frequent with cladribine (placebo, 1.8%; low cladribine, 21.6%; high cladribine, 31.5%), as was herpes zoster (placebo, 0.0%; low cladribine, 1.9%; high cladribine, 2.4%). Malignancies were seen as isolated cases across different organ systems. Of the 2 deaths in each treatment group, cladribine appeared to contribute to 1 of them, where a woman who had pulmonary pneumonia was found to have tuberculosis upon a postmortem examination. Patients should be screened for tuberculosis before administration of the drug, Dr. Giovanni noted. Funding for these studies was provided by Merck Serono SA. [Presentation titles: Reductions in MRI Activity in Relapsing-Remitting Multiple Sclerosis Achieved With Cladribine Tablets in the 96-Week, Phase III, Double-Blind, Placebo-Controlled CLARITY Study. Abstract P469 and Clinical Outcomes With Cladribine Tablets in the 96-Week, Phase III, Double-Blind, Placebo-Controlled CLARITY Study in Patients With Relapsing-Remitting Multiple Sclerosis. Abstract P470 and Safety and Tolerability of Cladribine Tablets in Relapsing-Remitting Multiple Sclerosis During the 96-Week, Phase III, Double-Blind, Placebo-Controlled CLARITY Study. Abstract O88]
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