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Objective: To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40mg compared to a 20mg dose. Methods: Patients with multiple sclerosis (MS) with ≥1 documented relapse in 12 months prior to screening, or ≥2 documented relapses in 24 months prior to screening, and Expanded Disability Status Scale (EDSS) score 0 to 5.5 were enrolled. Patients were evaluated at screening, baseline, and at months 1, 2, 3, 6, 9, and 12. Primary endpoint was rate of confirmed relapses observed during 12-month study. Analysis was by intent-to-treat. Results: A total of 1,155 patients randomized to GA 20mg (n = 586) or 40mg (n = 569). The groups were well-matched at baseline on demographic, clinical, and magnetic resonance imaging (MRI) characteristics. The primary endpoint was similar in both groups (relative risk [RR] = 1.07; 95% confidence interval [CI], 0.88–1.31; p = 0.486) with mean annualized relapse rates (ARRs) of 0.33 for the 20mg group, 0.35 for the 40mg group, and 0.27 for patients from both groups who completed the entire 1-year treatment. A total of 77% of patients remained relapse-free in both groups. Both groups showed a reduction in mean number of gadolinium-enhancing and new T2 lesions over time with trend for faster reduction in the first trimester with the 40mg dose compared with 20mg dose. Both doses were well-tolerated with a safety profile similar to that observed in previous studies of 20mg GA. Interpretation: In relapsing-remitting MS patients, both the currently-approved GA 20mg and 40mg doses were safe and well-tolerated, with no gain in efficacy for the higher dose. Ann Neurol 2011;69:75–82.

Summary Background Interferon beta-1a and glatiramer acetate are commonly prescribed for relapsing-remitting multiple sclerosis (RRMS), but no published randomised trials have directly compared these two drugs. Our aim in the REGARD (REbif vs Glatiramer Acetate in Relapsing MS Disease) study was to compare interferon beta-1a with glatiramer acetate in patients with RRMS. Methods In this multicentre, randomised, comparative, parallel-group, open-label study, patients with RRMS diagnosed with the McDonald criteria who had had at least one relapse within the previous 12 months were randomised to receive 44 μg subcutaneous interferon beta-1a three times per week or 20 mg subcutaneous glatiramer acetate once per day for 96 weeks to assess the time to first relapse. A subpopulation of 460 patients (230 from each group) also had serial MRI scans to assess T2-weighted and gadolinium-enhancing lesion number and volume. Treatments were assigned by a computer-generated randomisation list that was stratified by centre. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00078338. Findings Between February and December, 2004, 764 patients were randomly assigned: 386 to interferon beta-1a and 378 to glatiramer acetate. After 96 weeks, there was no significant difference between groups in time to first relapse (hazard ratio 0·94, 95% CI 0·74 to 1·21; p=0·64). Relapse rates were lower than expected: 258 patients (126 in the interferon beta-1a group and 132 in the glatiramer acetate group) had one or more relapses (the expected number was 460). For secondary outcomes, there were no significant differences for the number and change in volume of T2 active lesions or for the change in the volume of gadolinium-enhancing lesions, although patients treated with interferon beta-1a had significantly fewer gadolinium-enhancing lesions (0·24 vs 0·41 lesions per patient per scan, 95% CI −0·4 to 0·1; p=0·0002). Safety and tolerability profiles were consistent with the known profiles for both compounds. The overall number and severity of adverse events were similar between the treatments and were not an important cause for discontinuation of the trial during the 96 weeks. Interpretation There was no significant difference between interferon beta-1a and glatiramer acetate in the primary outcome. The ability to predict clinical superiority on the basis of results from previous studies might be limited by a trial population with low disease activity, which is an important consideration for ongoing and future trials in patients with RRMS. Funding EMD Serono; Pfizer.

Analyses of shallow cores obtained at the European Project for Ice Coring in Antarctica (EPICA) drilling site Kohnen station (758000 S, 008040 E; 2892ma.s.l.) on the plateau of Dronning Maud Land reveal the presence of conserved snow dunes in the firn. In situ observations during three dune formation events in the 2005/06 austral summer at Kohnen station show that these periods were characterized by a phase of 2 or 3 days with snowdrift prior to dune formation which only occurred during high wind speeds of >10ms–1 at 2m height caused by the influence of a low-pressure system. The dune surface coverage after a formation event varied between 5% and 15%, with a typical dune size of (4 2)m (8 3) m, a maximum height of 0.2 0.1m and a periodicity length of about 30 m. The mean density within a snow dune varied between 380 and 500 kgm–3, whereas the mean density at the surrounding surface was 330 5kgm–3. The firn cores covering a time-span of 22 2 years reveal that approximately three to eight events per year occurred, during which snow dunes had been formed and were preserved in the firn.