Multiple Sclerosis
Emerging Therapies in Multiple Sclerosis— New Decisions in the Formulation of Treatment Strategies
Guy J Buckle, MD, MPH Director of Clinical Care, Partners Multiple Sclerosis Center, Brigham and Women’s Hospital, and Assistant Professor of Neurology, Harvard Medical School
Abstract
The therapeutic options available to neurologists treating multiple sclerosis (MS) are profoundly changing. Hitherto, disease modifying therapies (DMTs) were entirely administered by injection and were only able to retard disease progression. The frequency of site reactions and flu-like symptoms has made adherence to treatment problematic and resulted in resistance from some patients. The recent approval of the first oral DMT in MS (fingolimod) and the development of other oral agents will provide much more attractive options to both physicians and patients and may promote earlier commencement of treatment. The development of the monoclonal antibody alemtuzumab may for the first time provide a MS treatment that will, in certain patients with relapsing disease, restore some degree of lost neurologic function. Therefore these new medications will fundamentally change the decision-making process from diagnosis to choice of treatment. However, these treatments do not address progressive disease. The challenge will be which MS patients should receive the new treatments and how much benefit such treatments will provide over current strategies.
Keywords Multiple sclerosis, disease-modifying therapies, new treatments, decision-making process
Disclosure: In the past 12 months, Guy J Buckle, MD, MPH, has received consulting fees from Acorda Therapeutics, Bayer, Biogen-Idec, EMD-Serono, Genzyme, Novartis, and Teva Pharmaceuticals. Acknowledgment: Editorial Assistance was provided by James Gilbart, PhD, at Touch Briefings. Received: October 6, 2010 Accepted: December 6, 2010 Citation: US Neurology, 2010;6(2):60–9 Correspondence: Guy J Buckle, MD, MPH, Director of Clinical Care, Partners Multiple Sclerosis Center, Brigham and Women’s Hospital, One Brookline Place, Suite 225, Brookline, MA 02445. E:
gbuckle@partners.org
Five of the currently-approved DMTs are given by injection at frequent intervals and have a range of adverse effects, notably ‘flu-like symptoms and injection site reactions. These effects can be a problem not only for patients who are newly prescribed the treatments, but also for some patients who experience ‘injection fatigue’ after years of continuous administration.2
The probable approval within
the next few years of a more effective monoclonal antibody treatment (alemtuzumab)3
fingolimod, teriflumomide, and BG00012)2,4–7
and several of the new oral DMTs (laquinimod, cladribine will represent a landmark
change that could substantially alter approaches to MS treatment. DMTs are widely used in the treatment of patients with MS in North America and have changed the prognosis in many patients for the better.8–10 However, in other territories they are often either not used commonly enough or not initiated early enough in the disease course to be effective. Factors including conservatism among physicians, delays in diagnosis and treatment initiation, fear of adverse events, and high cost or limited healthcare coverage can limit DMT use in these regions.
60
The Impact of Current Disease-modifying Therapies on Prognosis
In 1993, the first pivotal trial of interferon beta-1β (IFNβ-1β) was published, illustrating its efficacy in relapsing–remitting MS (RRMS).11 That same year, this drug was also made commercially available. Since then, a number of injectable DMTs have been approved for use in MS treatment, including IFNβ-1α and glatiramer acetate. These drugs all reduce relapse rates and magnetic resonance imaging (MRI) activity and appear to slow disease progression.12,13
Unfortunately, several factors
hinder researchers from assessing the true impact that current therapies have on MS disease course. First, there is a lack of natural
© TOUCH BRIEFINGS 2010
Disease-modifying therapies (DMTs) for treating multiple sclerosis (MS) are entering a period of rapid and profound change that will greatly expand treatment options and improve quality of life for the approximately 2.5 million people worldwide who suffer from this chronic, disabling disease.1
The aim of this article is to consider the way in which existing treatments have changed the outlook for MS patients and to assess the intravenous and oral treatments currently in late-stage development. Once given regulatory approval, these therapies are likely to have a dramatic effect on the choice and convenience of MS treatments. Therefore, it is timely to discuss the decision-making process neurologists go through prior to initiating treatment and during ongoing treatment and to reflect on the impact these novel therapies will have on this process.
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