The Burden of Disease

Transcription

1 The Burden of Disease A closer look at the consequences of living with multiple sclerosis 2011 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by MS.US.PO E your gateway to MS knowledge. Powered by 1

2 What is MS? MS is a chronic, variable disease of the central nervous system (CNS) MS is among the most common neurologic diagnoses cited as the cause of disability Worldwide, MS affects an estimated 2.1 million people More than 400,000 Americans have MS, and a new diagnosis is made every hour MS is variable and can present many challenges Loss of independence Decreased quality of life (QoL) Increasing limitations on mobility, cognition, and other physiologic functions Powered by 2

3 The burden of MS The true burden of MS falls on more than the healthcare system Powered by 3

4 Patients ultimately pay the price MS can cause symptoms that interfere with a patient s QoL and ability to function The consequences of MS are profound Increased unemployment Life expectancy is reduced by 5-10 years Strain on marriage and personal relationships Tolerability may be a concern with MS therapies Powered by 4

5 Dependence on caregivers can be overwhelming As the patient s ability to perform activities of daily living declines, dependence on caregivers increases Caregivers often face significant burdens Powered by 5

6 MS patients are vulnerable to noncompliance There are a range of barriers to adherence or causes of noncompliance Forgetting to administer therapy Fatigue Adverse events Needing a break from therapy Perceived lack of efficacy Problems injecting Powered by 6

7 Many factors constitute the true burden of MS Powered by 7

8 The burden of disease: What is the financial burden of MS? 2011 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by MS.US.PO E your gateway to MS knowledge. Powered by 8

9 MS is a costly disease Average costs estimated at $47,215 per patient per year (2004 data) * Estimated distribution does not equal 100% due to rounding. Powered by 9

10 EDSS score is a strong predictor of total cost Mean annual costs per patient nearly double from mild disability to severe disability Increased costs due to higher need for informal care, services, and investment to adapt the environment for the patient Powered by 10

11 The burden of disease: How does MS affect daily life? 2011 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by MS.US.PO E your gateway to MS knowledge. Powered by 11

12 MS affects patient independence Multiple impairments compound one another to create a synergistic, rather than additive, disabling effect Powered by 12

13 Mobility is the most frequently reported impairment in MS Two thirds of patients report trouble walking 94% say mobility impairment interrupts their overall daily life 70% of people with mobility impairment say it is the most challenging aspect of MS Walking impairment among people with MS is directly associated with loss of independence, restrictions on the ability to work, and reduction in household income Powered by 13

14 Causes of mobility changes also affect daily functioning Primary, secondary, and tertiary causes of mobility changes in MS Powered by 14

15 The burden of disease: Should there be more awareness of cognitive dysfunction? 2011 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by MS.US.PO E your gateway to MS knowledge. Powered by 15

16 Cognitive dysfunction affects daily function Up to 65% of MS patients have some form of cognitive impairment Remission of cognitive symptoms is uncommon in MS Powered by 16

17 Impact of MS starts early Cognitive impairment is seen in the CIS stage of disease Deficits were found mainly in memory, speed of information processing, attention, and executive functioning Powered by 17

18 Irreversible damage occurs early Cognitive dysfunction can be present even when other signs and symptoms are absent However, medications may negatively impact cognitive functioning EDSS does not adequately assess a patient s cognitive function EDSS assesses 8 functional systems: pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other Axonal damage and decreased brain volume can usually be seen prior to the clinical onset of MS Brain atrophy correlates with increased cognitive dysfunction Powered by 18

19 Barriers to cognitive testing exist Barriers to cognition testing must be overcome Access to neuropsychological services Cost of evaluations Increased staff time/training Early axonal damage and the reduced benefit of treatment later in the disease suggest that disease-modifying therapies should be initiated earlier in the course of MS Powered by 19

20 The burden of disease: Is benign MS truly benign? 2011 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by MS.US.PO E your gateway to MS knowledge. Powered by 20

21 Benign MS is highly prevalent Benign MS is characterized by a symptomatic period followed by full recovery with normal functioning, achieving a state of permanent arrest Although there is no consensus, benign MS is commonly defined as EDSS 3.0 (ie, mild disability) years after disease onset Estimates of the prevalence of benign MS vary widely and range from 5%-40%, depending on definition Patients with benign MS are reassured that disabling symptoms or loss of function are unlikely to occur as they would for patients with MS A significant percentage, however, can develop a secondary progressive course or progress in disease severity and accumulate noteworthy disability Powered by 21

22 Patients with benign MS experience debilitating symptoms Powered by 22

23 Benign MS can lead to significant disability progression In a 20-year longitudinal follow-up of patients with benign MS, almost half had progressed to EDSS scores >3.0 21% of patients with benign MS advanced to EDSS >6 In this study, 23% of patients had converted to secondary progressive MS by the 20-year follow-up Powered by 23

24 Benign and early MS: To treat or not to treat? Early axonal damage and the reduced benefit of treatment later in the disease suggest that disease-modifying therapies should be initiated earlier in the course of MS Early treatment may limit the damage caused by early disease and thereby minimize or delay the impact of the illness on long-term function Powered by 24

25 The burden of disease: Can early signs of disease indicate poorer prognosis? 2011 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by MS.US.PO E your gateway to MS knowledge. Powered by 25

26 MRI metrics may predict disease progression Studies indicate that certain MRI metrics may have predictive value in MS T2 lesions at the very early stages of the disease Changes in brain atrophy Brain atrophy can indicate demyelination and axonal loss in T2 lesions and tissue of normal-appearing white and gray matter Brain tissue loss correlates with clinical disability, and the rate of progression of brain atrophy in relapsing-remitting MS is predictive of long-term disability Powered by 26

27 Frequent early relapses lead to more rapid disease progression Relapses within the first 2 years have important prognostic significance and are a predictor of disability Relapses after 2 years have less impact on the rate of progression and have little impact on the time to increased disability DSS = disability status scale. Powered by 27

28 New advances may help predict disease progression and response to treatment Therapeutic efficacy biomarkers Neutralizing antibodies (NAbs) Interleukin-17 Gene expression profiling Proteomics Antigen microarray Powered by 28

29 Quality of life worsens as disability progresses Changes in EDSS significantly affect health-related QoL Physical component summary (PCS) is derived from the SF-36, a QoL measurement that complements the EDSS Higher EDSS scores were associated with lower PCS scores Powered by 29

30 The burden of disease: Can patients bear the burden of disease progression as a result of suboptimal response? 2011 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by MS.US.PO E your gateway to MS knowledge. Powered by 30

31 Factors leading to suboptimal treatment response Efficacy Failure to reduce relapses, breakthrough relapses, new lesions, progressing disability Tolerability Injection site reactions, depression, fatigue, flu-like symptoms Safety PML, malignancies, herpesvirus infection, lymphopenia, bradycardia, AV block Mode of administration Daily injections, daily oral dosing, monthly infusions Powered by 31

32 Despite disease-modifying therapy, disease often continues to progress The natural course of relapsing-remitting MS Powered by 32

33 Proposed criteria for identifying patients with suboptimal response Clinical status measured by serial history and examination Relapse rates of >1 per year, or failure to reduce annual relapse rate after 6-12 months of disease-modifying therapy Incomplete recovery from repeated relapses Relapses affecting multiple neurologic systems Subjective impression indicated by diminished function not reflected by neurologic exam finding Worsening neurologic impairment sufficient to disrupt daily activities, irrespective of changes on exam provided that influence of depression, medication, or concurrent disease is eliminated MRI indicators of active disease New or recurrent brainstem or spinal cord lesions Powered by 33

34 How should we identify suboptimal treatment response? Should factors other than relapse be considered? EDSS progression Brain atrophy Increased cognitive symptoms Many unmet needs still exist Induction of disease remission Reduction in number of relapses and increase in time between relapses Stopping or even improving EDSS or disability progression for a substantial period Is one relapse too many? Powered by 34

35 Can disease-modifying therapy go further? Identifying appropriate patients to treat early and aggressively may help prevent rapid worsening of disability Treatment goals should encompass: Freedom from disease Reversing disability Halting disease progression Increasing patient well-being Are currently available treatments doing enough to control symptoms of MS? Powered by 35

36 How can we lift the burden of MS? 2011 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by MS.US.PO E your gateway to MS knowledge. Powered by 36

37 Can evolving treatment parameters lead to improvement in disability? Powered by 37

38 MS is among the most common neurologic diseases affecting young adults The true burden of MS lies outside the healthcare system MS can cause symptoms that interfere with a patient s quality of life Even patients with benign MS may suffer debilitiating symptoms, such as cognitive impairment, significant fatigue, and depression Up to 65% of MS patients have some form of cognitive impairment In MS, multiple impairments compound one another synergistically Biggest incremental cost in MS occurs when patients transition from independent ambulatory status (EDSS 3.0), with severe disability costing an estimated $64,492 a year* Brought *Cost estimate to you by is from a study published your in gateway to MS knowledge. Powered by 38

39 MS treatment must provide more Despite disease-modifying therapy, disease often continues to progress Even with recent advances in the treatment of MS, substantial unmet needs remain MS treatment success should evolve to include higher goals: Improvements in physical and mental quality of life Freedom from MS disease activity Durable improvements in disability The opportunity exists to recognize that early intervention will provide a meaningful change in the course of MS. Powered by 39

40 Recommended follow-up resources 2011 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by MS.US.PO E your gateway to MS knowledge. Powered by 40

41 References Amato MP, Zipoli V, Goretti B, et al. Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort. J Neurol. 2006;253: Axtell RC, de Jong BA, Boniface K, et al. T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis. Nature Med. 2010;16: Bethoux F, Bennett S. Enhancing mobility in multiple sclerosis. Int J MS Care. 2011;13:1-3. Cascione M, Freedman MS. Achieving long-term gains with early intervention. MS News Online. January Cohen BA, Khan O, Jeffery DR, et al. Identifying and treating patients with suboptimal responses. Neurology. 2004;63:S33-S40. Copaxone prescribing information. Teva Neuroscience, Inc Costello K, Kennedy P, Scanzillo J. Recognizing nonadherence in patients with multiple sclerosis and maintaining treatment adherence in the long term. Medscape J Med. 2008;10(9): Accessed June 27, Dunn J. Impact of mobility impairment on the burden of caregiving in individuals with multiple sclerosis. Expert Rev Pharmacoecon Outcomes Res. 2010;10: Ewing C, Bernard CCA. Insights into the aetiology and pathogenesis of multiple sclerosis. Immunol Cell Biol. 1998;76: Feuillet L, Reuter F, Audoin B, et al. Early cognitive impairment in patients with clinically isolated syndrome suggestive of multiple sclerosis. Mult Scler. 2007;13: Powered by 41

42 References (continued) Filippi M, Rovaris M, Inglese M, et al, for the ETOMS Study Group. Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet. 2004;364: Freedman MS, Cohen B, Dhib-Jalbut S, et al. Recognizing and treating suboptimally controlled multiple sclerosis: steps toward regaining command. Curr Med Res Opin. 2009;25: Ghaffar O, Feinstein A. The neuropsychiatry of multiple sclerosis: a review of recent developments. Curr Opin Psychiatry. 2007;20: Gilenya prescribing information. Novartis Pharma Stein AG Goodin DS, Bates D. Treatment of early multiple sclerosis: the value of treatment initiation after a first clinical episode. Mult Scler. 2009;15: Halper J, Ross AP. Challenges in the treatment of mobility loss and walking impairment in multiple sclerosis. Int J MS Care. 2010;12: Harris Interactive for the National MS Society and Acorda Therapeutics. Key findings from two new multiple sclerosis surveys. National Multiple Sclerosis Society website. Accessed June 15, Houtchens MK, Benedict RHB, Killiany R, et al. Thalamic atrophy and cognition in multiple sclerosis. Neurology. 2007;69: 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: Powered by 42

43 References (continued) Kujala P, Portin R, Ruutiainen J. The progress of cognitive decline in multiple sclerosis: a controlled 3-year follow-up. Brain. 1997;120: Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33: McCrory DC, Pompeii LA, Skeen MB, et al. Criteria to Determine Disability Related to Multiple Sclerosis. Evidence Report/Technology Assessment No AHRQ Publication No. 04-E Rockville, MD: Agency for Healthcare Research and Quality, Miller DH, Barkhof F, Frank JA, Parker GJM, Thompson AJ. Measurement of atrophy in multiple sclerosis: pathologic basis, methodological aspects and clinical relevance. Brain. 2002;125: Morales-Gonzáles JM, Benito-León J, Rivera-Navarro J, Mitchell AJ, for the GEDMA Study Group. A systematic approach to analyse health-related quality of life in multiple sclerosis: the GEDMA study. Mult Scler. 2004;10: National Multiple Sclerosis Society. Facts about MS [fact sheet] /fundraising-information/fundraising-resources/download.aspx?id= Accessed August 7, National Multiple Sclerosis Society. Multiple Sclerosis: Just the Facts [brochure]. Accessed June 5, Paolillo A, Piattella MC, Pantano P, et al. The relationship between inflammation and atrophy in clinically isolated syndromes suggestive of multiple sclerosis: a monthly MRI study after triple-dose gadolinium-dtpa. J Neurol. 2004;251: Powered by 43

44 References (continued) Patti F, Amato MP, Trojano M, et al, for the COGIMUS Study Group. Cognitive impairment and its relation with disease measures in mildly disabled patients with relapsing-remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study. Mult Scler. 2009;15: Pfleger CCH, Flachs EM, Koch-Henriksen N. Social consequences of multiple sclerosis. Part 2. Divorce and separation: a historical prospective cohort study. Mult Scler. 2010;16: Quintana FJ, Farez MF, Viglietta V, et al. Antigen microarrays identify unique serum autoantibody signatures in clinical and pathologic subtypes of multiple sclerosis. Proc Natl Acad Sci U S A. 2008;105: Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology. 1991;41: Rebif prescribing information. EMD Serono, Inc Rudick RA, Miller D, Hass S, et al, for the AFFIRM and SENTINEL Investigators. Health-related quality of life in multiple sclerosis: effects of natalizumab. Ann Neurol. 2007;62: Sayao AL, Devonshire V, Tremlett H. Longitudinal follow-up of benign multiple sclerosis at 20 years. Neurology. 2007;68: Scalfari A, Neuhaus A, Degenhardt A, et al. The natural history of multiple sclerosis, a geographically based study 10: relapses and long-term disability. Brain. 2010;133: Tysabri prescribing information. Elan Pharmaceuticals, Inc Powered by 44

45 References (continued) Trapp BD, Ransohoff RM, Fisher E, Rudick RA. Neurodegeneration in multiple sclerosis: relationship to neurological disability. Neuroscientist. 1999;5: Weiss DB, Beresford TP, House RM. Noncompliance in neurologic patients. Curr Treat Options Neurol. 2005;7: Powered by 45