Dr. Robertson is director of the Multiple Sclerosis Center of Excellence at James A. Haley Veterans' Hospital in Tampa, Florida. Dr. Moreo is a PGY-1 multiple sclerosis fellow, and Dr. Robertson is an assistant professor of neurology and director of the multiple sclerosis division, both at the University of South Florida in Tampa.
Author disclosures Dr. Robertson has served as a consultant for Biogen, Genzyme, Teva Neuroscience, and Pfizer; is on the speakers’ bureaus of Biogen, Pfizer, EMD Serono, Genzyme, Novartis, Teva Neuroscience, Mallinckrodt, and Acorda; and has received grant support from Biogen, Genzyme, Novartis, Sun Pharma, MedImmune, Actelion, Mallinckrodt, EMD Serono, and Genetech.
Disclaimer The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Certain clinical indicators, such as higher relapse rates early in the disease course and MRI characteristics, including total lesion burden and the location of lesions within the CNS, seem to be associated with a higher risk of disease progression.56 These are potential prognostic indicators that can help tailor the choice of disease-modifying therapy for patients.57 Those with highly inflammatory and potentially aggressive disease at onset, for example, may benefit from early initiation of higher efficacy therapies, whereas those with more benign forms of MS at onset may fare well on lower efficacy therapies. In general, when it comes to currently available MS treatments, higher efficacy is often tied to riskier AE profiles, so the best medication may be the “least efficacious” one that can still control the disease.20
Hauser and colleagues suggested a treatment decision-making model that identifies the interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide as acceptable first-line therapies; fingolimod and natalizumab as acceptable second-line options; and mitoxantrone and alemtuzumab as acceptable third-line therapeutic options.20 The authors generally agree with Hauser and colleagues’ model, and it is important to consider individual patient factors (eg, comorbidities, concurrent medications, life circumstances) and disease severity when deciding on a treatment plan.
Perhaps an even more difficult question is, when is the right time to switch therapies? There remains a dearth of either guidelines or comparative studies for treatment management decisions. Further, without reliable biomarkers, the clinical and pathologic heterogeneity of MS makes treatment difficult.4,19 In practice, there is general consensus that 1 year of treatment monitoring for effects on clinical and radiologic outcomes is an acceptable time frame to evaluate effectiveness of a disease-modifying treatment. If adherence is maintained and there is still evidence of clinical or MRI activity (suggesting a suboptimal response), an alternative therapy, particularly one with a different MOA, should be strongly considered. This highlights the importance of broad access to all available MS therapies to allow for early selection of a correct therapy that patients will remain adherent to and that controls their disease.
Multiple sclerosis remains a highly unpredictable disease, and relapses have the ability to produce a measurable and sustained impact on the level of disability.58 Still, the influence of reduced relapses on preventing disability in an individual patient remains unclear. Large, long-term, prospective cohort studies may clarify whether early treatment affects disease progression and disability.20 However, it is quite evident that effective relapse reduction decreases discomfort, reduces days lost from work and other important activities of daily life, and improves QOL.58,59
There is still much to learn about this unique disease, but emerging evidence in the medical literature highlights the importance of setting treatment goals that include targeting disease activity to achieve early and effective control. Attaining control with a MS medication seems to be a key component of slowing the physical and emotional disability that can accumulate, helping patients remain active and maintain the highest QOL possible for as long as possible.
