Supplements Best Practices for Natalizumab Utilization in the Treatment of Multiple Sclerosis
Quantifying the Role of Natalizumab in Health and Economic Outcomes in Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system defined by inflammation, demyelination, and axonal degeneration. MS progresses slowly and usually strikes at a fairly young age, causing both the direct and indirect costs of treating the disease to be very high. The direct costs to treat MS can average up to $30,000 per year; including indirect costs raises this to as high as $47,000. Natalizumab has proven to be able to reduce the signs of MS and has been associated with improvements in health-related quality-of-life measures; these effects have the potential to also reduce some of the economic burden of this debilitating disease. The significant clinical burden of MS can be quantified by cost and societal impact, important information to both payers and employers.
(Am J Manag Care. 2010;16:S171-S177)
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by inflammation, demyelination, and axonal degeneration. In the United States, there are an estimated 400,000 people with MS.1 Most patients are diagnosed between the ages of 20 and 50 years, but MS can afflict both younger and older persons.1
MS is a disease that afflicts many people who have their most productive years ahead. The economic burden associated with MS can be considerable, especially when taking into account both direct costs (eg, MS-specific healthcare) and indirect costs (eg, lost ability to work). The purpose of this article is to quantify the burden of MS in terms of domains that directly or indirectly affect economic outcomes, and identify the economic impact of natalizumab on those same outcomes.
The Clinical Burden of MS
MS is a progressive disease that can be disabling as early as 6 years after diagnosis, with permanent disability often occurring within 10 years after diagnosis if not properly treated.2 Disease progression can be quantified using the Expanded Disability Status Scale (EDSS).3 EDSS scores range from 0 to 10; a score of 0 indicates no disability, while a score of 10 indicates death due to MS. It is a nonlinear scale with emphasis on ambulation. Mild MS (ie, patients without ambulatory difficulty) is defined as an EDSS score less than 4.0, moderate MS (ie, those with some ambulation impairment) have an ED SS score between 4.0 and 6.0, and more severe MS (ie, patients with significant ambulation impairment) is defined by scores greater than 6.0. With more severe MS, mechanical assistance is utilized. The use of unilateral equipment (eg, cane, crutch, brace) begins with a score of 6.0, and wheelchair use begins with a score of 7.0. As shown in Figure 1, the level of disability in untreated MS generally increases over time.2 On average, patients who are not receiving treatment have ED SS scores of 4.0 or higher by the 7th year after initial diagnosis.
The disabilities that patients with MS experience are numerous and are not just physical disabilities. Cognitive impairment is a major concern for MS patients. Chiaravalloti and DeLuca noted that cognitive impairment affects 43% to 70% of patients with MS.4 Cognitive impairment in patients with MS usually relates to slowed mental processing speed and difficulty with memory recall and multitasking. Basic intelligence is usually not affected. These patients frequently cannot "keep up" with coworkers. Thus, a decline in cognitive function may be the major reason many patients with MS are unable to work. Over half of patients with MS are unemployed within 10 years of diagnosis, and this is often attributed to a decline in cognition.4
One of the most common physical disabilities in MS patients is overwhelming physical fatigue. Based on a Canadian study of 85 patients, a total of 40% report fatigue on a daily basis; 69% of these patients stated that fatigue was the worst, or one of the worst, symptoms of MS.5 Other common symptoms of MS include numbness, gait disturbances, poor balance and coordination, bladder and/or bowel dysfunction, visual impairment, dizziness, vertigo, sexual dysfunction, pain, and spasticity.6
Overall, the decline in physical and mental function associated with MS greatly impacts quality of life. Rudick et al examined health-related quality of life (HRQOL) in patients enrolled in 2 large phase 3 clinical trials (SENTINEL [Safety and Efficacy of Natalizumab in Combination with Interferon beta-1a] and AFFIRM [Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis]). Using the Short Form-36 instrument, which is complementary to the ED SS and provides a generic (ie, not specific to MS patients) measure of HR QOL, it was observed that baseline physical and mental component summary scores were significantly lower than the general population.7 Not surprisingly, HRQOL was directly related to the severity of MS as well as to whether the patient was experiencing a relapse (defined as a period of worsening neurologic function).
The Economic Burden of MS
The economic burden associated with MS is daunting, and includes considerable medical and nonmedical expenditures. With regard to medical costs, a study by Kobelt et al estimated total direct medical costs of MS to be $29,634 per year (2004 dollars); total costs including indirect costs were $47,215.8
Another US study reported the average annual costs for the direct care of MS to be $12,879 (2004 dollars).9 Compared with the costs reported above by Kobelt et al, there is a visible dissimilarity, which was due to methodology. The analysis by Prescott et al utilized costs for medical care taken directly from administrative claims data specific to MS (as compared with information from survey data mapped to costs used by Kobelt et al). Additionally, the patient population differed; the latter analysis represented a larger percentage of patients not currently using disease-modifying treatments (DM Ts). Among patients receiving DMTs, reported costs were closer to those in the Kobelt et al study. The analysis by Prescott and colleagues also noted that MS costs were dependent on the general health of the patient; patients reporting symptoms such as gait abnormality, ataxia, convulsions, malaise/ fatigue, optic neuritis, or spasms had significantly higher total costs.9
Generally, the cost of MS is dependent on its severity. A study based in Europe estimated the total mean annual costs per patient (2005 values) to be €18,000 ($22,500) for mild MS (EDSS score <4.0), €36,500 ($45,625) for moderate MS (EDSS score 4.0-6.5), and €62,000 ($77,500) for severe MS (EDSS score >7.0).10 Interestingly, this study noted that direct medical costs (including pharmacy) were fairly even among the 3 categories, while indirect costs increased sharply with increased severity. A similar pattern was observed in the United States, where informal costs rose dramatically with increased severity of disease (Figure 2).8 In this latter study, informal care referred to the time spent by family and friends caring for a patient with MS. A study from Germany showed a similar pattern; the average annual cost of MS to the payer was €18,988 ($23,735 [2005 dollars]) while the cost to society was €39,998 ($49,998).11 A large portion of the societal costs were informal care and loss of productivity/early retirement. The authors of this study also noted that as MS progresses, patients must purchase walking aids and wheelchairs, modify cars/houses for handicap access, and rely on family and friends for some form of help. They calculated that if a patient with MS requires approximately 500 hours of assistance per year, this results in an additional cost of €4400 ($5500) per patient.11 A recent presentation by Miltenburger and Gunther also showed that the cost of informal care for patients with MS was much higher as the disease progressed.12 In Germany, 70% of informal care costs were allocated for patients with EDSS scores greater than 7. In Italy, 82% of early retirement costs and 92% of informal care costs were related to caring for patients with EDSS scores greater than 5.0.
Impact of Natalizumab on Clinical Outcomes
The introduction of natalizumab in 2006 gave clinicians a new treatment option for relapsing MS. The landmark AFFIRM study showed that natalizumab reduced the risk of sustained progression of disability over 2 years by 42% (hazard ratio [HR ], 0.58; 95% confidence interval [CI ], 0.43-0.77; P <.001); reduced the rate of clinical relapse at 1 year by 68% (0.23 vs 0.73, respectively; P <.001), which was maintained at 2 years; and reduced the accumulation of new or enlarging T2 hyperintense lesions by 83% (mean number of lesions, 1.9 with natalizumab and 11.0 with placebo; P <.001), as detected by magnetic resonance imaging.13
In addition to these clinical outcome improvements, natalizumab was also shown to improve quality-of-life measures in patients with MS. For example, Rajagopalan et al measured MS-specific quality-of-life measures using the Multiple Sclerosis Impact Scale-29 in patients receiving natalizumab (n = 296) over the course of 6 infusions and found that patients had significant improvements in both physical and psychological scores (physical impact score: baseline 48 ± 23, third infusion 40 ± 23, sixth infusion 40 ± 25 [P <.0001]; psychological impact score: baseline 41 ± 22, third infusion 33 ± 21, sixth infusion 33 ± 23 [P <.0001]).14 Similarly, a small study reported improvements with natalizumab in selfreported fatigue, cognition, and weakness in 70% (41/59), 68% (40/59), and 68% (40/59) of patients, respectively.15