Perspectives for managed care organizations on the burden of multiple sclerosis and the cost-benefits of disease-modifying therapies.

Disease-modifying therapies (DMTs) are a core component of multiple sclerosis (MS) management. Given current constraints on health care expenditures, the relative cost-effectiveness of these therapies needs to be considered when making treatment decisions. The objective of this article is to review the burden of illness of MS, discuss the cost-effectiveness data for DMTs, and summarize the implications for payers. For the burden of illness in MS, a retrospective analysis of managed care administrative data from the IMS LifeLink Health Plan Claims Database was performed. Data from claims submitted for patients with confirmed MS (ICD-9-CM code 340) over a period of 1 year (2009) were analyzed. A literature review was conducted to put these data into perspective. The retrospective analysis determined that the mean annual cost of treating MS in the United States in 2009 was $23,434, which varied according to the presence of comorbidities/complications. Overall, DMTs accounted for 69% of the total costs of managing the disease. According to the literature review, the typical first-line DMTs (interferon beta [IFNß] formulations and glatiramer acetate [GA]) are generally associated with incremental cost-utility or cost-effectiveness ratios in excess of $100,000 per quality of life year gained. Natalizumab may have cost benefits over other agents in patients with more aggressive disease. According to the available data, studies indicate that DMT cost-effectiveness (specifically cost per quality-adjusted life years) appears to improve with treatment initiation during the early stages of the disease. In relapsing-remitting MS, there is currently little evidence to differentiate between the DMTs that are typically used first-line (IFNs and GA) based on cost-effectiveness or cost-utility studies. Presently, optimal therapy decisions for DMT-naïve patients are likely to be made individually based on patient and provider preference, adherence, and medication risk-benefit profiles. For patients with more advanced disease, natalizumab appears to have greater efficacy and to be more cost-effective than other agents.

Contemporary pharmacologic treatments for spasticity of the upper limb after stroke: a systematic review.

BACKGROUND: Muscle spasticity after stroke may be painful and severe and may restrict the patient's ability to perform routine daily tasks, particularly when the affected muscles are in the upper limbs. Treatments targeted at reducing this spasticity have evolved over time. OBJECTIVE: This was a systematic review of recent studies focusing on contemporary pharmacologic therapies for upper limb spasticity after stroke. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched for clinical trials published in English from January 1995 to July 2010 using search terms that included spasticity, stroke, hemiplegia, phenol, baclofen, tizanidine, dantrolene, benzodiazepine, and botulinum toxin. The level of evidence of the identified publications was assessed using the Oxford Centre for Evidence-Based Medicine criteria. RESULTS: A total of 113 potentially relevant articles were identified by the search; of these, 54 studies were included in the review (23 randomized controlled trials [RCTs] and 31 open-label, nonrandomized, or observational studies). Of these, 51 involved treatment with botulinum toxin (BTX). All studies assessed spasticity; some also assessed additional outcomes, such as pain, disability, and functional status. Thirty-eight clinical trials reported a significant reduction in spasticity with BTX, either compared with baseline or with placebo (P < 0.05). A head-to-head comparison found a significant reduction in spasticity with BTX injections compared with oral tizanidine (TZD) (P < 0.001). Two studies of intrathecal baclofen (ITB) reported significant reductions in upper limb spasticity after 12 months of treatment, and 1 study of tizanidine reported significant reductions in upper limb spasticity after 16 weeks of treatment (all, P < 0.001). General or local weakness, injection-site pain, and fatigue were the most frequently reported adverse events with BTX type A, and dry mouth was the most frequently reported adverse event with BTX type B. No serious or life-threatening adverse events were reported in any trial of BTX. CONCLUSIONS: The 54 studies included in this systematic review of treatments for upper limb spasticity after stroke measured multiple outcomes using a variety of instruments. Fifty-one studies focused on treatment with a BTX formulation. BTX appeared to be an effective and well-tolerated focal treatment for reducing tonicity in patients with upper limb spasticity after stroke, supporting current guideline recommendations.

The diagnosis of asthma and exercise-induced bronchospasm in division I athletes.

OBJECTIVE: To determine the accuracy of clinically diagnosed exercise-induced bronchospasm (EIB) and asthma among National Collegiate Athletic Association Division I student athletes. DESIGN: Cohort study. SETTING: Division I university athletic department and primary care sports medicine clinic/athletic training room. PATIENTS: All varsity athletes were eligible for the study. Seventy-five participants entered the study; 74 completed all the study protocols. INTERVENTIONS: Study participants underwent measurement of exhaled nitric oxide (eNO), followed by baseline spirometry. Eucapnic voluntary hyperventilation (EVH) was then performed, followed by spirometry every 3 minutes for a total of 21 minutes to measure change in forced expiratory volume in 1 second. MAIN OUTCOME MEASURES: Exhaled nitric oxide levels, baseline spirometry, and response of forced expiratory volume in 1 second to EVH. RESULTS: There were a total of 16 subjects with a positive EVH test. There were 16 (80%) individuals using a bronchodilator who had a negative EVH test versus 4 (20%) who had a positive test. Mean eNO values were different across subject groups defined by treatment status, although not statistically significant. The highest mean eNO value of 24.32 ppb was found in subjects only taking bronchodilators compared with the lowest mean value of 16.75 ppb in athletes who were not taking any medications. CONCLUSIONS: The results from this study provide further evidence to support the need for objective testing to correctly diagnose EIB. These data suggest that measuring eNO may help to distinguish truly isolated EIB from asthma in athletes, but a larger study is needed to confirm these initial observations.

The cost-effectiveness of sertraline in the treatment of depression.

Depressive disorders are common conditions that place a large burden of illness on patients, employers, payers, and society. Although efficacious interventions exist to treat various forms of the condition, substantial gaps in care remain. The selective serotonin re-uptake inhibitors (SSRIs) represent the most commonly utilized drug class for the treatment of depression; sertraline is the most prescribed single agent and received generic drug approval in 2006. The results of pharmacoeconomic analyses comparing the costs and outcomes of sertraline with other antidepressants are mixed; in particular, investigations emphasize branded medications relative to costs. Continued research is needed to support decision making given recent changes in the antidepressant marketplace, particularly the introduction of generic sertraline and newer agents, and the complexity that surrounds the management of depressive disorders.

Cost-effectiveness of urokinase and alteplase for treatment of acute peripheral artery disease: comparison in a decision analysis model.

PURPOSE: The cost-effectiveness of urokinase and alteplase for the treatment of acute peripheral artery disease (PAD) was compared using decision analysis. METHODS: A literature-based decision model to evaluate cost-effectiveness was constructed using a base case of a 65-year-old man with acute PAD. Successful treatment outcomes were defined as clot lysis with a subsequent 30-day survival posttreatment. Direct medical costs were assessed from the payer perspective in the United States and analyzed using sensitivity analyses. A Monte Carlo analysis with 5000 patients was performed to obtain mean and incremental cost-effectiveness ratios (ICERs). RESULTS: The mean cost-effectiveness ratio was $67,581 (95% confidence interval [CI], $36,899 to $108,836) per 30-day treatment success for alteplase and $78,729 (95% CI, $43,411 to $130,063 for urokinase). The ICER for urokinase relative to alteplase was $332,309 per additional 30-day treatment success (95% CI, $-565,540 to $1,661,247). Approximately 75% of simulated cases indicated that urokinase was associated with increased costs and increased treatment success compared with alteplase. Results of a post hoc sensitivity analysis indicated that dominance decreased to approximately 10% of cases only under the most strict criteria. CONCLUSION: Decision analysis found an ICER of $332,309 per additional 30-day treatment success for urokinase relative to alteplase in the treatment of PAD from the perspective of the payer in the United States. In about 75% of cases resulting from a Monte Carlo simulation, urokinase was associated with increased costs and slightly increased treatment success compared with alteplase, although this finding was sensitive to the distributional assumptions made concerning certain costs in the model.