Glatiramer acetate is an approved drug for relapsing-remitting multiple sclerosis (MS). An Article published Online First (www.thelancet.com) and in an upcoming edition of the Lancet shows that early treatment with this drug can reduce by almost half the risk of patients progressing from the very early signs of MS to clinically definite disease. The Article is written by Professor Giancarlo Comi, Department of Neurology, University Vita-Salute, Milan, Italy, and colleagues.
In around 85% of patients eventually diagnosed with MS, the first the first clinical event is an acute and usually spontaneously remitting episode that suggests a lesion in the central nervous system—known as clinically isolated syndrome. However, not all patients with this syndrome develop MS and, of those that do, prognosis is highly variable. For instance, after 15-20 years from clinical onset, about half will have major disability, and up to a third will have little or no disability. Clinical and MRI evidences suggests that early treatment can prevent or delay accumulation of irreversible neuronal damage.
This randomised, double-blind trial took place at 80 sites in 16 countries. 481 patients presenting with a clinically isolated syndrome were randomly assigned to receive either subcutaneous glatiramer acetate 20 mg per day (n=243) or placebo (n=238) for up to 36 months, unless they converted to clinically definite MS. The primary endpoint was time to clinically definite MS, based on a second clinical attack. A preplanned interim analysis was done for data accumulated from 81% of the 3-year study exposure.
Glatiramer acetate reduced the risk of developing clinically definite MS by 45% compared with placebo. The time for 25% of patients to convert to clinically definite disease was more than doubled, from just under a year for placebo to just under two years for glatiramer acetate. The most common adverse events in the glatiramer acetate group were injection-site reactions (56% glatiramer acetate vs 24% placebo) and immediate post-injection reactions (19% vs 5%).
The authors note that the robustness of the positive results was emphasised by the concomitant efficacy of glatiramer acetate in reducing all the MRI measures of disease activity (ie, evidence of MS-related lesions in the brain). In a post-hoc analysis based on all patients who completed 2 years of the study without converting to clinically definite multiple sclerosis, they noted a significant reduction of the cumulative number of new T2 lesions in patients receiving glatiramer acetate versus those receiving placebo, both in the four and in the eight scans done during the first year and the entire 2 years, respectively. The results of this study reiterate the key importance of early treatment in MS to contrast the accumulation of irreversible nervous damage.
The authors conclude: "This study establishes glatiramer acetate as an option for patients with clinically isolated syndrome who choose to start treatment early to improve control of the underlying disease process."
In an accompanying Comment, Dr David H Miller, UCL Institute of Neurology, London, UK, and Dr Siobhan M Leary National Hospital for Neurology and Neurosurgery, London, UK, conclude: "The greatest unmet therapeutic need in multiple sclerosis is to identify treatments that delay, prevent, and even reverse progressive irreversible disability; strategies focused on neuroprotection and repair—in addition to or instead of immunomodulation— might be needed to achieve this goal."
Professor Giancarlo Comi, Department of Neurology, University Vita-Salute, Milan, Italy. T) +39 02 2643 2990 E) comi.giancarlo@hsr.it
Dr David H Miller, UCL Institute of Neurology, London, UK. Contact by e-mail only. E) d.miller@ion.ucl.ac.uk
For full Article and Comment, see: http://press.thelancet.com/precisefinal.pdf
Journal
The Lancet