Differentiating societal costs of disability worsening in multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS), confirmed disability progression (CDP) can be either the result of progression independent of relapse activity (PIRA) or relapse-associated worsening (RAW). However, the economic effect of PIRA and RAW on societal economic costs in patients with MS is not well understood. OBJECTIVE: To determine societal economic costs of patients achieving disease activity free status (DAF) and compare them with those having PIRA and RAW events. METHODS: We used a roving EDSS score analysis to detect PIRA and RAW events with confirmation after at least 6 months. We estimated the age-, gender-, EDSS-adjusted effects of PIRA and RAW on total, direct medical, direct non-medical and indirect societal economic costs. Patients achieving DAF were assigned to as reference. RESULTS: Overall, 1959 patients were analyzed. Total mean quarterly societal economic costs including disease-modifying therapies (DMTs) were 6929€ (SD: 2886€) per patient averaged over a period of 2 years. Excluding DMTs, patients achieving DAF had total mean quarterly costs of 1703€ (SD: 2489€). PIRA caused 29% (IRR: 1.29; CI 1.06-1.50, p < 0.05) higher total costs compared to DAF. On the contrary, RAW increased total costs by factor 1.56 (CI 1.30-1.87, p < 0.001). The effect of PIRA and RAW was striking for direct medical costs which increased by factor 1.48 (95% CI 1.13-1.95, p < 0.01) and 2.25 (95% CI 1.72-2.94, p < 0.001), respectively. CONCLUSION: Disease progression increases societal economic costs significantly. Thus, delaying or even preventing disease progression in MS may reduce the societal economic burden of MS.

Natalizumab: a review of its use in the management of relapsing-remitting multiple sclerosis.

Natalizumab (Tysabri®) is a humanized monoclonal antibody against the α4 chain of integrins and was the first targeted therapy to be approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Natalizumab acts as a selective adhesion molecule antagonist, which binds very late antigen (VLA)-4 and inhibits the translocation of activated VLA-4-expressing leukocytes across the blood-brain barrier into the CNS. In a pivotal phase III clinical trial, natalizumab 300 mg intravenously every 4 weeks for 2 years in adults with RRMS significantly reduced the annualized relapse rate and the risk of sustained progression of disability compared with placebo, as well as significantly increasing the proportion of relapse-free patients at 1 and 2 years. Natalizumab also significantly reduced the number of T2-hyperintense, gadolinium-enhancing and T1-hypointense lesions on magnetic resonance imaging, and significantly reduced the volume of T2-hyperintense and T1-hypointense lesions compared with placebo. Natalizumab recipients generally experienced improved health-related quality of life at 1-2 years. Natalizumab was generally well tolerated in pivotal trials. The only adverse events that were more frequent with natalizumab monotherapy than with placebo were fatigue and allergic reactions. The main safety and tolerability issue with natalizumab is the incidence of progressive multifocal leukoencephalopathy (PML). As long as the risk of PML is managed effectively, natalizumab is a valuable therapeutic option for adults with highly active relapsing forms of multiple sclerosis.

Comparative effectiveness of early natalizumab treatment in JC virus-negative relapsing-remitting multiple sclerosis.

OBJECTIVES: To estimate the long-term comparative effectiveness of first-line treatment in patients negative for anti-JC virus (JCV) antibodies with glatiramer acetate (GA), fingolimod, or natalizumab for relapsing-remitting multiple sclerosis (RRMS). STUDY DESIGN: We developed a simulation model to estimate the average 20-year clinical risks and benefits of GA, fingolimod, and natalizumab for RRMS patients initially negative for anti-JCV antibodies. METHODS: Model inputs included published natural history progressions of the Expanded Disability Status Scale (EDSS), treatment effects from randomized controlled trials on slowing disease progression and reducing relapse rates, risk of progressive multifocal leukoencephalopathy (PML), and utility preference scores. Outputs were long-term risks (PML risk and other non-PML risks), benefits (average relapse rate and time to disability [EDSS >7]), and quality-adjusted life years (QALYs). RESULTS: Compared with GA, natalizumab resulted in 4.6 fewer relapses, 0.6 more years of disability free time, 0.0165 more cases of PML per treated patient, and an incremental 1.2 QALYs gained. Compared with fingolimod, natalizumab resulted in 1.7 fewer relapses, 0.1 more years of disability free time, 0.0165 more cases of PML per treated patient, and an incremental 0.4 QALYs gained. The probability that incremental QALYs favored natalizumab over GA was 0.963 and natalizumab over fingolimod was 0.720. CONCLUSIONS: Average QALYs, a measure that aggregates across risks and benefits, favored natalizumab, suggesting more aggressive early intervention with natalizumab in the negative anti-JCV population. For certain decision makers, more evidence may be needed to further reduce the uncertainty in these comparative projections prior to making population-based adoption decisions.

A cost-effectiveness analysis of subcutaneous interferon beta-1a 44mcg 3-times a week vs no treatment for patients with clinically isolated syndrome in Sweden.

OBJECTIVE: To assess the cost-effectiveness of subcutaneous interferon (sc IFN) beta-1a 44 mcg 3-times weekly (tiw) vs no treatment at reducing the risk of conversion to multiple sclerosis (MS) in patients with clinically isolated syndrome (CIS) in Sweden. METHODS: A Markov model was constructed to simulate the clinical course of patients with CIS treated with sc IFN beta-1a 44 mcg tiw or no treatment over a 40-year time horizon. Costs were estimated from a societal perspective in 2012 Swedish kronor (SEK). Treatment efficacy data were derived from the REFLEX trial; resource use and quality-of-life (QoL) data were obtained from the literature. Costs and outcomes were discounted at 3%. Sensitivity analyses explored whether results were robust to changes in input values and use of Poser criteria. RESULTS: Using McDonald criteria sc IFN beta-1a was cost-saving and more effective (i.e., dominant) vs no treatment. Gains in progression free life years (PFLYs) and quality-adjusted life-years (QALYs) were 1.63 and 0.53, respectively. Projected cost savings were 270,263 SEK. For Poser criteria cost savings of 823,459 SEK were estimated, with PFLY and QALY gains of 4.12 and 1.38, respectively. Subcutaneous IFN beta-1a remained dominant from a payer perspective. Results were insensitive to key input variation. Probabilistic sensitivity analysis estimated a 99.9% likelihood of cost-effectiveness at a willingness-to-pay threshold of 500,000 SEK/QALY. CONCLUSION: Subcutaneous IFN beta-1a is a cost-effective option for the treatment of patients at high risk of MS conversion. It is associated with lower costs, greater QALY gains, and more time free of MS. LIMITATIONS: The risk of conversion from CIS to MS was extrapolated from 2-year trial data. Treatment benefit was assumed to persist over the model duration, although long-term data to support this are unavailable. Cost and QoL data from MS patients were assumed applicable to CIS patients.

A comparative study of self-efficacy in men and women with multiple sclerosis.

The purpose of this study was to examine if there was a difference in the level of self-efficacy between men and women with relapsing-remitting multiple sclerosis (RRMS) and progressive forms of multiple sclerosis (MS). A quantitative, descriptive, comparative design was used. The convenience sample included 556 individuals with MS, of which 124 were men (73 RRMS and 51 progressive MS) and 432 women (348 RRMS and 84 progressive MS). Participants completed the Multiple Sclerosis Self-Efficacy Scale (MSSE). This study found gender differences in self-efficacy among those living with MS. The women had a significantly greater belief in their ability to function with MS. The women also had a greater belief in their ability to control their MS than the men, although the difference was not significant. This study also found significant differences in self-efficacy between those with RRMS and those with progressive forms of MS. When men were compared by type of MS, those with RRMS had significantly greater belief in their ability to control their disease and function with it than those with progressive forms of MS. For women, those with RRMS had significantly greater belief in their ability to control their MS and function with it than women with progressive forms of MS. Individuals with MS could benefit from strategies that enhance self-efficacy. Such strategies include providing skills for self-management of MS, providing education and support of the patient and family, introducing the patient to a role model with MS, encouraging physical reconditioning, and referring to a support group that will meet individualized needs.

Cost of managing an episode of relapse in multiple sclerosis in the United States.

BACKGROUND: The purpose of this study was to determine the direct medical US cost of managing multiple sclerosis relapses. METHODS: Direct data analysis and cost modeling were employed to derive typical resource use profiles and costs in 2002 US dollars, from the perspective of a third-party payer responsible for comprehensive health-care. The location and scope of health care services provided over a 90-day period were used to define three levels of relapse management. Hospitalization and resulting subsequent care was defined as high intensity management. A medium level of intervention was defined as either use of the emergency room, an observational unit, or administration of acute treatments, such as intravenous methylprednisolone in an outpatient or home setting. The lowest intensity of care comprised physician office visits and symptom-related medications. Data were obtained from many sources including all payer inpatient, ambulatory and emergency room databases from several states, fee schedules, government reports, and literature. All charges were adjusted using cost-to-charge ratios. RESULTS: Average cost per person for high management level was 12,870 dollars, based on analysis of 4,634 hospital cases (mean age 48 years, 73% female). Hospital care comprised 71% of that cost. At discharge, 36% required inpatient sub-acute care, rehabilitation or home care. The typical cost per moderate episode was 1,847 dollars and mild episode 243 dollars. CONCLUSIONS: Management strategies leading to a reduction in the frequency and severity of a relapse, less reliance on inpatient care, or increased access to steroid infusions in the home, would have a substantial impact on the economic consequences of managing relapses.