Monitoring and Treating Multiple Sclerosis: Advances in 2010

Treatment and monitoring of patients with multiple sclerosis (MS) made important strides in 2010, according to a review in Nature [2011;7:74-75]. Magnetic resonance imaging (MRI) and immunologic biomarkers were identified to track the evolution of the disease and guide clinical decisions regarding treatment. Also, 2010 saw the emergence of oral disease-modifying therapies designed to increase medication regimen adherence and to improve patient outcomes. Because of MRI’s high sensitivity for revealing focal white matter lesions, use of the imaging technology is particularly useful in the diagnosis of patients suspected of having MS. There are diagnostic MRI criteria for patients presenting with clinically isolated syndromes suggestive of MS. These criteria allow clinicians to exclude the presence of alternative neurologic conditions and to demonstrate disease dissemination in space and time sooner and with more certainty than with clinical assessment alone. When MS is diagnosed early, clinicians are able to begin treatment in the early stages of the disease, which has been shown to have a positive effect on the course of the disease. Working with earlier diagnostic MRI criteria for MS, the European Multicenter Collaborative Research Network on MRI in MS (MAGNIMS) has developed a new set of MRI-based criteria. An MRI scan performed at any time that demonstrates disease dissemination in space and showing the simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions (the latter being used as evidence for disease dissemination in time) is considered sufficient to diagnose MS using the new criteria. An MRI scan performed at any time that shows disease dissemination in space but no enhancing lesions would require further imaging. The MAGNIMS criteria simplify the earlier criteria, but maintain a high specificity for MS. Specificity is essential to minimize false-positive diagnoses. For patients with MS, the disease can take variable courses, so effective and accessible biomarkers are needed to enable clinicians to monitor the progression of the disease and make informed decisions about treatment. Immunologic biomarkers promise to provide an alternative to MRI markers for monitoring disease progression. A study reported in Brain [2010;133:1602-1611] quantified complement factor H and its Tyr402His polymorphic variant in serum from 350 patients with MS. The researchers found that factor H levels were significantly higher in patients with progressive MS compared with healthy patients or patients with relapsing-remitting multiple sclerosis (RRMS). The serum factor H levels allowed clinicians to distinguish cases of secondary progressive MS from RRMS, the researchers said. MS research in 2010 also focused on defining the impact of neutralizing antibodies (NAbs) on progression of MS. A study reported in Archives of Neurology [2010;67:402-407] found that 24% of study participants with RRMS were NAb-positive after a median interval of 25 months following cessation of treatment, and that the presence of persistent NAbs was associated with an increase in annual rate of relapse, reduction in time to reach a sustained score on 6 on the Expanded Disability Status Scale, and a greater probability of switching to second-line therapies. Two large, double-blind, randomized, placebo-controlled phase 3 trials evaluating the efficacy of oral treatments for MS were completed and published in 2010. The FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis) trial evaluated oral fingolimod for the treatment of RRMS. Study participants were assigned to receive 0.5 mg of fingolimod daily, 1.25 mg, or placebo. Compared with the placebo group, patients in the 2 treatment groups had a decreased annual relapse rate and a reduced risk of disability progression during the follow-up period. Cladribine, an MS drug administered orally, also gained attention in 2010. The CLARITY (Cladribine Tablets Treating Multiple Sclerosis Orally) trial was a 96-week, placebo-controlled phase 3 study designed to evaluate the safety and efficacy of cladribine at doses of 3.5 and 5.25 mg/kg of body weight. Patients in the 2 treatment groups had a decreased annualized rate of relapse, an increased relapse-free rate, and a decreased risk of 3-month sustained progression in disability compared with patients in the placebo group. The review authors noted that the observed treatment effects for both fingolimod and cladribine and the method of administration of the drugs are “likely to markedly increase patients’ adherence in treatment regimens and, ultimately, improve treatment responses.” They cautioned, however, that the “beneficial effects of both drugs will need to be weighed against the adverse events and long-term risks associated with their use, which will only become apparent in the postmarketing phase of these agents, as was the case for natalizumab.”