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| |  Atorvastatin Decreases New Brain MRI T2 Lesion Activity in Patients With Clinically Isolated Syndrome: Presented at ECTRIMS By Chris Berrie DÜSSELDORF, Germany -- September 16, 2009 -- Atorvastatin significantly decreased new brain magnetic resonance imaging (MRI) T2 lesion activity in patients with clinically isolated syndrome (CIS), despite not meeting its primary endpoint due to discontinuation of enrolment, researchers noted here at the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). This multicentre, double-blind, phase 2 trial was presented here on September 12 by principal investigator Emmanuelle Waubant, MD, PhD, Department of Neurology, University of California, San Francisco, San Francisco, California. Oral statin use previously has shown indications of decreased MRI activity in patients with multiple sclerosis (MS). Said Dr. Waubant, “The objective [of this trial] was to test the efficacy and safety of oral atorvastatin 80 mg/day compared with placebo in patients with CIS.” Subjects included in the trial were all adults (18 to 55 years) with CIS of 48 hours or greater duration seen within 90 days of symptom onset, with 2 or more silent T2-bright lesions of 3 mm or greater diameter. The primary endpoint was for development of 3 or more T2-bright brain foci or 1 new clinical exacerbation during 12 months of treatment, with the calculated need for a sample of 152 patients. With discontinuation of enrolment due to slow recruitment, however, the study was underpowered to detect the planned effect size. In all, 81 patients were randomised, with 32 receiving placebo and 49 receiving atorvastatin 80 mg/day for 12 months. Baseline characteristics indicated a mean age of 33.8 years, 76.5% female, and a mean duration of time from symptom onset of 66 days. Baseline MRI features indicated higher values for atorvastatin over placebo for mean numbers of T2 lesions (21.6 vs 19.5) and gadolinium-enhancing (Gd+) lesions (0.7 vs 0.2). “These differences were not statistically significant,” Dr. Waubant noted, “but could actually have bias against defining the treatment in the atorvastatin group.” The patient presentation of CIS included: optic neuritis, 40.7%; spinal-cord syndrome, 34.6%; brainstem/cerebellar, 17.3%; and other, 6.2%. In all, 56.3% placebo subjects and 49.0% atorvastatin-treated patients met the primary endpoint (P = .650). “The time for half of the patients to meet the primary endpoint was about 280 days in the [placebo] group, whereas it was almost 400 days in the atorvastatin group,” Dr. Waubant commented. As a secondary endpoint, freedom from new T2 lesions was significantly increased in atorvastatin- treated patients over placebo subjects: 55.3% versus 27.6% (P = .032). The possibility of remaining free of T2 lesions was also significantly higher for atorvastatin-treated patients versus placebo subjects, with an odds ratio (OR) of 3.93 (P = .012; 2-stage regression). Similarly, there was a trend in favour of treated patients regarding the possibility of patients remaining Gd+ lesion-free, with an OR of 2.70 (P = .078; 2-stage regression). In the safety analysis, atorvastatin showed some increase over placebo for adverse events (AEs) leading to treatment discontinuation (18.4% vs 12.5%), or decrease or interruption (24.5% vs 3.1%), although there were no increases in SAE incidence (4.1% vs 3.1%) or grade 3 or higher AEs (16.3% vs 12.5%). The increased AEs potentially related to atorvastatin use were nausea (28.6% vs 9.4%), alanine aminotransferase increase (18.4% vs 3.1%), and aspartate aminotransferase increase (16.3% vs 3.1%), although there were no changes for myalgia (10.2% vs 12.5%) or creatine phosphokinase (8.2% vs 6.3%). While this study did not meet its primary endpoint, Dr. Waubant concluded, it does provide indications of improved disease activity with atorvastatin treatment that require further investigation in larger trials. Funding for this study was provided by Pfizer Inc. [Presentation title: Atorvastatin Therapy in Patients With Clinically Isolated Syndrome and High-Risk for Conversion to Multiple Sclerosis: The STAyCIS Study. Abstract 132]
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