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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2007.12.035 Byline: Matt Fisher (a), Mary Cushman (b), Volker Knappertz (a), George Howard (c) Abstract: The use of aspirin alone and statins alone has been shown to reduce markers of inflammation, including C-reactive protein (CRP); however, their combination has been poorly studied. Author Affiliation: (a) Bayer HealthCare, Morristown, NJ (b) University of Vermont, Burlington, VT (c) University of Alabama-Birmingham, Birmingham, AL Article History: Received 21 June 2007; Accepted 26 December 2007 Article Note: (footnote) [star] This research project is supported by a cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, and Department of Health and Human Services. The authors acknowledge the participating investigators and institutions: University of Alabama at Birmingham, Birmingham, AL (Study PI, Data Coordinating Center, Survey Research Unit ): George Howard, Leslie McClure, Virginia Howard, Libby Wagner, Virginia Wadley, Rodney Go; University of Vermont, Burlington, VT, (Central Laboratory): Mary Cushman; Wake Forest University, Winston-Salem, NC, (ECG Reading Center): Ron Prineas; Alabama Neurological Institute, Birmingham, AL, (Stroke Validation Center, Medical Monitoring): Camilo Gomez, David Rhodes, Susanna Bowling, Sean Orr; University of Arkansas for Medical Sciences, Little Rock, AR, (Survey Research): LeaVonne Pulley; Examination Management Services Incorporated, Scottsdale, AZ, (In Home Visits): Andra Graham; National Institute of Neurological Disorders and Stroke, National Institutes of Health (funding agency): Claudia Moy., [star][star] Matt Fisher and Volker Knappertz are employees of Bayer HealthCare.

Multiple sclerosis (MS) is a chronic, progressive, disabling disorder characterized by immune-mediated demyelination, inflammation, and neurodegenerative tissue damage in the central nervous system (CNS), associated with frequent exacerbations and remissions of neurologic symptoms and eventual permanent neurologic disability. While there are several MS therapies that are successful in reducing MS relapses, none have been effective in treating all patients. The specific response of an individual patient to any one of the MS therapies remains largely unpredictable, and physicians and patients are forced to use a trial and error approach when deciding on treatment regimens. A priori markers to predict the optimal benefit-to-risk profile of an individual MS patient would greatly facilitate the decision-making process, thereby helping the patient receive the most optimal treatment early on in the disease process. Pharmacogenomic methods evaluate how a person's genetic and genomic makeup affects their response to therapeutics. This review focuses on how pharmacogenomics studies are being used to identify biologically relevant differences in MS treatments and provide characterization of the predictive clinical response patterns. As pharmacogenomics research is dependent on the availability of longitudinal clinical research, studies concerning glatiramer acetate and the interferon beta products which have the majority of published long term data to date are described in detail. These studies have provided considerable insight in the prognostic markers associated with MS disease and potential predictive markers of safety and beneficial response. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To assess, from a Swedish societal perspective, the cost effectiveness of interferon β-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). Methods: A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. Results: In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. Conclusion: Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs. [Copyright &y& Elsevier]

Abstract: Background: Clinical trials have shown that treatment with disease-modifying therapies (DMTs), such as interferon, at the time of clinically isolated syndrome can delay the onset of multiple sclerosis (MS). Objectives: The objective of this study was to assess health care utilization and expenditures associated with treating patients early with DMTs rather than delaying until patients meet the full diagnostic criteria of MS. Methods: A retrospective study used insurance claims data (2000–2008) of enrolled patients before documented MS (1 inpatient or 2 outpatient claims with International Classification of Diseases, 9th Revision, Clinical Modification 340 coding). Treatment cohorts were early DMT (DMT claim before the first documented MS; N = 227) and delayed DMT (DMT started after documented MS; N = 3724). Comparisons during 1 year of follow-up were adjusted for confounding using multivariate methods. Results: Adjusted annual per-patient expenditures (including patient out of pocket) for early versus delayed were as follows: total ($28,280 vs $29,102; P = 0.44), excluding DMT cost ($15,214 vs $17,630; P < 0.01), and MS-related ($9365 vs $13,661; P < 0.01). Hospitalizations were 10.1% versus 16.5% (adjusted odds ratio [OR] = 0.51; 95% CI, 0.32–0.81). Conclusions: Analysis indicated that early DMT treatment was associated with fewer hospitalizations than delayed treatment, and there was no statistically significant difference in annual health care expenditures. This suggests that the drug costs of early therapy were offset by savings in other medical expenditures. [Copyright &y& Elsevier]

Summary: Background: The aim of the Betaferon Efficacy Yielding Outcomes of a New Dose (BEYOND) trial was to compare the efficacy, safety, and tolerability of 250 μg or 500 μg interferon beta-1b with glatiramer acetate for treating relapsing-remitting multiple sclerosis. Methods: Between November, 2003, and June, 2005, 2447 patients with relapsing-remitting multiple sclerosis were screened and 2244 patients were enrolled in this prospective, multicentre, randomised trial. Patients were randomly assigned 2:2:1 by block randomisation with regional stratification to receive one of two doses of interferon beta-1b (250 μg or 500 μg) subcutaneously every other day or 20 mg glatiramer acetate subcutaneously every day. The primary outcome was relapse risk, defined as new or recurrent neurological symptoms separated by at least 30 days from the preceding event and that lasted at least 24 h. Secondary outcomes were progression on the expanded disability status scale (EDSS) and change in T1-hypointense lesion volume. Clinical outcomes were assessed quarterly for 2·0–3·5 years; MRI was done at screening and annually thereafter. Analysis was by per protocol. This study is registered, number NCT00099502. Findings: We found no differences in relapse risk, EDSS progression, T1-hypointense lesion volume, or normalised brain volume among treatment groups. Flu-like symptoms were more common in patients treated with interferon beta-1b (p<0·0001), whereas injection-site reactions were more common in patients treated with glatiramer acetate (p=0·0005). Patient attrition rates were 17% (153 of 888) on 250 μg interferon beta-1b, 26% (227 of 887) on 500 μg interferon beta-1b, and 21% (93 of 445) for glatiramer acetate. Interpretation: 500 μg interferon beta-1b was not more effective than the standard 250 μg dose, and both doses had similar clinical effects to glatiramer acetate. Although interferon beta-1b and glatiramer acetate had different adverse event profiles, the overall tolerability to both drugs was similar. Funding: Bayer HealthCare Pharmaceuticals. [Copyright &y& Elsevier]