PROCEEDINGS ECONOMICS OF MULTIPLE SCLEROSIS AND ITS TREATMENT* — Jacquelyn L. Bainbridge, PharmD, FCCP† ABSTRACT Multiple sclerosis (MS) is a chronic, severely disabling disease that typically makes its first appearance during young adulthood or early middle age. The lifetime treatment costs of MS exceed the costs of other disabling neurologic conditions, such as stroke or Alzheimer’s disease. Patients with MS have healthcare expenses that far exceed the expenses of typical patients with health insurance, with some studies suggesting average annual direct treatment costs exceeding $20 000 per patient. Nationwide treatment costs in the United States exceed $7 billion per year, and MS treatment costs have risen during the past several years with the introduction of disease-modifying agents, such as interferon beta and glatiramer acetate. Treatment algorithms or guidelines have recently been proposed to improve the cost-effective delivery of MS care. These approaches include the use of a steppedcare treatment algorithm that is based on a “platform” of immunosuppressive therapy. The stepped-care approach provides recommendations or interventions to improve treatment adherence, at-home treatment of MS exacerbations, and the use of specialty pharmacy companies to administer complex and costly MS treatments. (Adv Stud Pharm. 2007;4(11):330-333) *This article is based on a presentation at a roundtable on April 10, 2007, in San Diego, California. †Associate Professor, Department of Clinical Pharmacy, University of Colorado at Denver and Health Sciences Center, Denver, Colorado. Address correspondence to: Jacquelyn L. Bainbridge, PharmD, Associate Professor, Department of Clinical Pharmacy, University of Colorado at Denver and Health Sciences Center, Academic Office 1, 12631E–17th Avenue, Room L15-1419, School of Pharmacy C238-L15, PO Box 6511, Aurora, CO 80045. E-mail: jacci.bainbridge@uchsc.edu. 330 M ultiple sclerosis (MS) is associated with considerable economic impact in the United States due to the chronic and progressive course of the disorder, unpredictability of exacerbations, extensive disability, high cost of treatment, and effects on employment and job performance. The typical age of onset of MS is relatively young (20–35 years), and the total lifetime economic impact is therefore greater than other severe, disabling neurologic conditions, such as stroke or Alzheimer’s disease.1 This paper provides an overview of the costs associated with MS care in the United States, and describes methods that have been developed to optimize the use of newer MS therapies in managed care settings. DIRECT AND INDIRECT COSTS OF MS Recent studies have attempted to define the direct treatment costs of MS, as well as the indirect economic impact that the disorder has on the lives of patients with MS. Although these studies vary in the specific patient populations that they have enrolled, in the ways that costs are estimated, and in the definitions of direct and indirect costs, they consistently describe MS as a disease with considerable long-term economic impact for patients, healthcare systems, and society as a whole. Prescott et al recently estimated direct MS treatment costs using data from 80 private and public health plans in the United States, with a total of more than 9 million patients.1 These investigators estimated that direct treatment costs totaled an average of $12 879 per patient in 2004, and that direct costs had increased by 35% between 1995 and 2004. Other studies that have used data from health plans or patient surveys have estimated average direct treatment costs of approximately $20 000 to $30 000 per year.2,3 The direct medical costs to treat a single MS relapse have Vol. 4, No. 11 n October 2007 PROCEEDINGS been estimated to vary from a mean of $243 for a mild episode, to $1847 for a moderately severe episode, and $12 870 for patients requiring the most intensive care.4 It has been estimated that patients with MS have total treatment costs that are approximately 3 times the costs of patients without MS, with out-of-pocket healthcare expenditures that are approximately double those of individuals without MS.5,6 Indirect treatment costs that fall outside the healthcare system (eg, sick leave, early retirement, environmental home modifications, and informal care from family and friends) are important contributors to the total economic impact of MS, but have not been analyzed consistently from study to study.7 A patient survey of the total economic impact of MS found that the annual average cost of MS (direct and indirect costs) was more then $34 000 per patient (in 1994 dollars), with a lifetime per-case cost of approximately $2.2 million.8 The total cost of MS care in the United States was conservatively estimated by these investigators at nearly $7 billion. Kobelt et al, in a recent large US nationwide survey, estimated that MS was associated with lost productivity costs of approximately $15 000 per patient per year, largely due to the effects of early retirement.3 Finally, despite differences in specific study patient populations or analysis methods, the direct and indirect costs increase markedly with worsening MS disability (as measured using scores on clinical rating scales, such as the Expanded Disability Status Scale).9 This suggests that treatments intended to slow or prevent MS disability have the potential to significantly reduce the total economic burden of MS.9 COST OF CARE: DRUGS, MONITORING, AND SIDE EFFECTS The proportion of MS treatment costs that are accounted for by drug costs has increased over the past decade, as a result of the introduction of newer disease-modifying drugs.3 Drug costs are now the largest single contributor to direct treatment costs for patients with MS.3 A study of MS spending in 55 health plans found that drug costs accounted for approximately 50% of total per-patient treatment costs.2 An analysis of healthcare claims data from more than 10 000 patients with MS found that pharmacy costs accounted for approximately 65% of direct healthcare costs for MS treatment overall, and 75% of total costs for patients who had a prescription for at least one diseasemodifying agent.1 In this study, total annual per- University of Tennessee Advanced Studies in Pharmacy n patient treatment costs were estimated at $16 928 for glatiramer acetate, $17 987 for interferon beta-1a for intramuscular (IM) administration, $19 616 for interferon beta-1b, and $22 557 for interferon beta-1a for subcutaneous (SC) administration. The current average wholesale price for these agents per year when given at the standard dose are $19 632 for interferon beta-1b, $18 360 for interferon beta-1a (IM), $21 163 for interferon beta-1a (SC), and $19 749 for glatiramer acetate. Natalizumab, which has recently reentered the marketplace, costs approximately $30 000 per year.10 In addition, estimates of patient out-ofpocket costs to obtain MS medications have varied from $500 to more than $3000 per year, a considerable economic barrier for many patients.2,11 Costs are also associated with treatment monitoring and side effects, although these costs have not been extensively studied in patients with MS. Total direct and indirect treatment costs associated with MS in a recent nationwide US study are summarized in the Table and Figure. TREATMENT ALGORITHMS TO IMPROVE COST-EFFECTIVE DELIVERY OF MS CARE Direct treatment costs increase in proportion to the frequency of exacerbations and severity of MS. Therefore, treatment algorithms that effectively reduce the number and severity of exacerbations have the potential to help managed care organizations to treat MS more effectively and with lower total cost.9 For example, Morrow has outlined a process to control costs of MS treatment in the managed care setting.12 The author emphasized that patients should be monitored for poor treatment adherence, and interventions should be employed as needed to improve treatment adherence (eg, home visits by specially trained MS nurses). Another component of cost control is to anticipate that a certain number of relapses will occur and to plan for home care, rather than hospitalization, for as many of these expected events as possible. Many managed care organizations are partnering with specialty pharmacy companies, which specialize in the administration of high-cost, difficult-to-administer medications. Rich et al have described the use of a stepped-care approach to MS treatment to reduce the number of MS exacerbations.13 This approach is based on the selection of a “platform” therapy to provide a basic degree of immunosuppression throughout the course of the disease, with the addition of other agents 331 PROCEEDINGS Table. Mean Total Cost Per Patient and Year Costs Total costs (SD) Cost per Person Share of and Year ($, 2004) Total Cost, % 47 215 (35 292) 100.0 Total direct costs (SD) 29 634 (17 553) 62.8 Hospital inpatient care 1245 2.6 Ambulatory care 1582 3.4 Day stays 165 0.3 Physicians 565 1.2 Nurses/physiotherapists 419 0.9 Paramedical 436 0.9 Tests 857 1.8 Drugs 18 628 39.5 Disease-modifying drugs (94% of sample) 16 050 34.0 Services 822 1.7 Adaptations 1885 4.0 Informal care 4614 9.8 Total indirect costs (SD) 17 581 (23 640) 37.2 Short-term absence 533 1.1 Reduced working time/ income 3362 7.1 Early retirement 13 685 29.0 may be used in addition to platform therapy if necessary; however, natalizumab is to be used only as monotherapy. CONCLUSIONS Due to the young age at onset, chronic course, severe disability, unpredictability of exacerbations, and other factors, treatment costs for MS total several billion dollars per year in the United States. Per-patient direct medical costs have been estimated at approximately $20 000 to $30 000 per year in recent studies, due largely to the cost of disease-modifying drugs. Indirect costs (eg, lost productivity and early retirement) also contribute to the considerable economic burden of MS for society as a whole. Approaches to improving the cost effectiveness of treatment in managed care settings have focused on the development of algorithms or other procedures to reduce the number and severity of MS relapses. Figure. Distribution of Costs Hospital inpatient care 3% Ambulatory care 4% Reprinted with permission from Kobelt et al. Neurology. 2006;66:16961702.3 Tests 2% as needed as the disease progresses. In this approach, interferon beta preparations or glatiramer acetate are recommended as platform therapy because they can decrease the number of relapses and brain lesions on magnetic resonance imaging. Treatment for several months may be required before therapy is completely effective, and patient education is therefore essential to help patients set realistic expectations about the effects of treatment. A number of other agents may be combined with platform therapy as needed to address specific symptoms, including baclofen or tizanidine for spasticity, stimulants for fatigue, selective serotonin reuptake inhibitors or other antidepressants for depression, and anticholinergic agents or alpha adrenergic antagonists for bladder dysfunction. Additional immunosuppressive or immunomodulatory agents (eg, mitoxantrone or natalizumab) may be used to treat breakthrough MS symptoms. Mitoxantrone 332 Early retirement 34% Disease modifying drugs 22% Prescription and OTC drugs 6% Sick-leave and reduced working time 10% Informal care 12% Services 2% Adaptations 5% Distribution of costs on different types of resources, adjusted for estimated national use of disease-modifying drugs (DMD). To estimate average costs for patients with multiple sclerosis in the United States, we adjusted the use of the new DMD to an estimated national average of 52%. No other costs were changed in the absence of data, as Expanded Disability Status Scale has been shown to be by far the strongest predictor of total costs (in the absence of a relapse). Under this assumption, mean total costs per patient and year would be approximately $40 000. OTC = over the counter. Reprinted with permission from Kobelt et al. Neurology. 2006;66:1696-1702.3 Vol. 4, No. 11 n October 2007 PROCEEDINGS REFERENCES 1. Prescott JD, Factor S, Pill M, Levi GW. Descriptive analysis of the direct medical costs of multiple sclerosis in 2004 using administrative claims in a large nationwide database. J Manag Care Pharm. 2007;13:44-52. 2. Goldman DP, Joyce GF, Lawless G, et al. Benefit design and specialty drug use. Health Aff (Millwood). 2006;25:1319-1331. 3. Kobelt G, Berg J, Atherly D, Hadjimichael O. Costs and quality of life in multiple sclerosis: a cross-sectional study in the United States. Neurology. 2006;66:1696-1702. 4. O’Brien JA, Ward AJ, Patrick AR, Caro J. Cost of managing an episode of relapse in multiple sclerosis in the United States. BMC Health Serv Res. 2003;3:17. 5. Minden SL, Frankel D, Hadden L, Hoaglin DC. Access to health care for people with multiple sclerosis. Mult Scler. 2007;13:547-558. 6. Pope GC, Urato CJ, Kulas ED, et al. Prevalence, expenditures, utilization, and payment for persons with MS in insured populations. Neurology. 2002;58:37-43. 7. Kobelt G. Economic evidence in multiple sclerosis: a review. Eur J Health Econ. 2004;5(suppl 1):S54-S62. University of Tennessee Advanced Studies in Pharmacy n 8. Whetten-Goldstein K, et al. A comprehensive assessment of the cost of multiple sclerosis in the United States. Mult Scler. 1998;4:419-425. 9. Patwardhan MB, Matchar DB, Samsa GP, et al. Cost of multiple sclerosis by level of disability: a review of literature. Mult Scler. 2005;11:232-239. 10. Hauser SL, Johnston SC. Recombinant therapeutics: from bench to bedside (if your health plan concurs). Ann Neurol. 2006;60:10A-11A. 11. Lundy J, Craig BM. The use of disease-modifying agents among multiple sclerosis patients enrolled in Medicare from 1995 to 2002 and the impact of Medicare part D: analysis of claims data from the Medicare current beneficiary survey. Clin Ther. 2006;28:140-145. 12. Morrow TJ. The costs and consequences of multiple sclerosis relapses: a managed care perspective. J Neurol Sci. 2007;256(suppl 1):S39-S44. 13. Rich SR, Coleman IC, Cook R, et al. Stepped-care approach to treating MS: a managed care treatment algorithm. J Manag Care Pharm. 2004;10(suppl B):S26-S32. 333