Multiple Sclerosis
In multiple sclerosis (MS), 2008 has been a big year in terms of diseasemodifying therapies. Results from key clinical trials presented at the 60th annual meeting of the American Academy of Neurology (AAN) revealed that high-dose interferon beta-1b (Betaferon®/Betaseron®, Bayer Schering Pharma) had little advantage in efficacy over its lowdose counterpart, and no clear superior efficacy could be discerned between interferon beta-1b or glatiramer acetate (Copaxone®, Teva Pharmaceuticals). Nor have any greater clinical benefits been found by doubling the standard dose of glatiramer acetate. Significantly, very strong evidence has been presented in support of early treatment with interferons and glatiramer acetate immediately following the initial MS attack. This strategy has been proposed as potentially delaying progression to clinically definite MS.

Also presented at the AAN meeting were updates on new and current therapeutics. The anti-CD52 monoclonal antibody alemtuzumab (Campath®, Genzyme/Bayer Schering Pharma) has been under investigation for the treatment of relapsing–remitting MS (RRMS). At three years, alemtuzumab was associated with significant reductions in relapse rate (73%) and risk for sustained accumulation of disability (71%) compared with the interferon beta-1a comparator; clinical trials continue that will help to define the role of alemtuzumab in RRMS. Positive results have also been reported for daclizumab (Zenapax®, Biogen Idec) and rituximab (Rituxan®/Mabthera®, Genentech/Biogen Idec/Roche). Natalizumab (Tysabri®, Biogen Idec/Élan), approved for monotherapy in MS patients who were unresponsive to or intolerant of alternate MS therapies, has been associated with an increased risk for progressive multifocal leukoencephalopathy (PML). With more than 40,000 natalizumabexperienced patients and no cases of PML, there was hope that the previous cases were due to interaction with concomitant therapies, controllable by natalizumab monotherapy. Sadly, two cases of PML have emerged this year in patients receiving natalizumab monotherapy for approximately 14 and 17 months. While the current indication for natalizumab remains unchanged, physicians are urged to be extra vigilant about any adverse effects observed. As all currently approved MS medications are available only as injectable formulations, there has been much interest oral agents and positive results from clinical trials have been reported this year for the following: vitamin D3, rolipram, ibudilast (MN-166, Avigen), laquinimod (Teva Pharmaceutical Industries and Active Biotech), cladribine (Leustatin®, Merck Serono), fingolimod (FTY720, NovartisPharma), and BG-12 (dimethyl fumarate, Biogen Idec).