Burden of Rheumatoid Arthritis

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Burden of Rheumatoid Arthritis
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(No Transcript)
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Burden of Rheumatoid Arthritis

• Individual
• Joint destruction
• Collateral damage
• Psychological
• Social
• Financial

• Society
• Work
• Healthcare costs
• Social care costs

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Burden of Rheumatoid Arthritis

• Disabling condition affecting 0.5-1 of the
  worldwide population
• Women more likely affected than men
• Average age of onset 45 prevalence increases
  with age
• Medical costs are 2-3 times higher than average
• Lost productivity costs are 2-3 times higher than
  medical costs

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Case 1 CH 25 femaleBackground

• 3-month history of generalised joint stiffness
• 1 month pain and swelling in fingers and wrists
• No recent history of significant infections

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Case 1 CH 25 femaleBackground

• Examination shows
• General examination normal
• Swelling of MCPs and PIPs
• Tender MCPs and PIPs
• Tender MTPs
• Reduced range of movement of shoulders
• DAS28 5.7

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Case 1 CH 25 femaleStandard investigations

• Investigations
• Hb 10.7 g/dL
• Plts 425 x109/L
• ESR 42 mm/hr
• Biochemistry normal
• CRP 37 mg/L
• ANA ve
• RF 50 IU

• X-rays hands and feet normal

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Case 1 CH 25 femaleFurther investigations

• USS hands
• Synovitis in MCPs with increased vascularity and
  suggestion of small erosion in head of 4th MC
• Anti-CCP
• Strongly positive

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Age Distribution of Rheumatoid Arthritis
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Burden of Rheumatoid Arthritis

• Inflammatory disorder primarily of the joints
• Progressive disease with flare-ups
• 70 have joint damage within 2 years
• 25 have severe functional problems after 10-15
  years of disease
• 16 likely to need hip or knee replacement

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The Burden of RACollateral Damage
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The Burden of RA Collateral Damage
Kirwan JR. J Rheumatol. 200128881-886 Scott
DL. Rheumatol. 20003924-29.
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CH 63 female

• RA 15 years ago
• RF strongly positive
• DAS28 2.83.5
• CRP 510
• Treated
• MTX 20mg/wk
• SSZ 1gm bd
• IM depomedrone PRN

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CH 63 female

• Erosions MCPs
• Knee pain with loss of joint space
• Other medical problems
• MI inferior 6 years ago
• NIDDM
• Osteoporosis

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Collateral Damage in RA Cardiovascular disease

• Patients with RA are at an increased risk of
  cardiovascular disease (CVD)
• Mortality due to CVD is increased by 50-100 in
  patients with RA
• There is also an increase in CVD morbidity in RA
• Independent of traditional risk factors

del Rincon ID et al. Arthritis Rheum 2001 44
273745.
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Burden of RA IHD in RA
Predictor IRR for MI 95 CI p-value

RA 2.23 (2.07, 2.41) lt0.001
RA (adjusted) 2.04 (1.82, 2.30) lt0.001

adjusted for Age, Sex, HTN, DM, Smoking, BMI,
Anti-HTN drugs, Lipid-lowering drugs ever before
MI DMARDs/Pred. at time of MI

• GPRD 34,963 RA cases 103,092 controls
• No difference in DM, HTN, anti-hypertensives or
  statins

Edwards et al ACR OP 687/688 2008
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Quality of Life
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Health-related quality of life
Physical
Depression
Cong. heart failure
Mental
Myocard. infarction
Arterial hypertonia
Cancer
Arthritis
Psoriasis
Healthy individuals
0
20
40
60
80
100
120
Physical and Mental Component Summary Score
Rapp S et al., J Am Ac Dermatol 199941401-407.
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Rheumatic Disease is a Leading Cause of Disability
Persons aged 15 years and olderCDC. Morbidity
and Mortality Weekly Report. 2001. 50(7) 120-125.
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The psychosocial impact of inflammatory disease

• Evidence base for psychological impact of
  inflammatory diseases is well-established
• Psoriasis 5.5 active suicidal ideation, 9.7
  wish to be dead9 Suicidal ideation outpatients
  2.5 inpatients 7.210
• Rheumatoid arthritis 11 outpatients reported
  suicidal ideation11

• Psoriasis
• Disability1
• Worry2
• Anxiety3
• Depression4

• Rheumatoid Arthritis
• Disability5
• Depression6,7
• Anxiety8

1. Finlay Coles. Br J Dermatol 1995 132
236-244 2. Fortune et al. Br J Heal Psychol
2000 5 71-82 3. Richards et al. J Psychosom
Res 2001 50 11-15 4. Esposito et al. Dermatol
2007 212123-127 5. Hill et al. Clin Rheumatol
2007 261049 1054 6. Pincus et al. Br J
Rheumatol 1996 35879-833 7. Escalante et al.
Arthritis Care Res 2000 13 156167 8. Katz
Yelin. Arthritis Care Res 1994 7 69-77. 9.
Gupta et al. Int J Dermatol 1993 32188-190
3.Gupta et al. Br J Dermatol 1998 139 846-850
4. Treharne et al. BMJ 2000 321 1290
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Quality of Life of Patients with RA vs. Patients
with Other Chronic Conditions
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Direct Indirect Cost of RA
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RA is Associated with Significant Direct and
Indirect Costs

• Compare economic burden to society incurred by
  patients with RA, OA or HBP
• Information collected on demographics, health
  status, comorbidities, and resource utilization
• RA 253 patients
• OA and/or HBP 473 patients
• Direct and indirect costs highest for patients
  with RA

Maetzel A, et al. Ann Rheum Dis. 2004 63
395-401.
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The Cost of RA by Functional Level
Sweden
UK
300
16
14
250
12
200
10
UK Sterling ( 1000)
Swedish Kronor (SEK 1000)
150
8
6
100
4
50
2
0
0
lt0.6
0.6 lt1.1
1.1 lt1.6
1.6 lt2.1
2.1 lt2.6
gt2.6
lt0.6
0.6 lt1.1
1.1 lt1.6
1.6 lt2.1
2.1 lt2.6
gt2.6
1 SEK 15 1 SEK 9.3, 0.6
Direct costs
Indirect costs
Kobelt G et al. Arthritis Rheum. 2002462310-9.
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Pathogenesis of Rheumatoid Arthritis (RA)
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The Inflammatory Cascade in RA

• Activation of T cells triggers a series of
  intercellular reactions1
• Lymphocytes, monocytes/ macrophages, and synovial
  fibroblasts are stimulated to release
  proinflammatory cytokines2
• Cytokines induce synovial proliferation and
  release of destructive enzymes1-3

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Mechanisms of Structural Damage in Rheumatoid
Arthritis1
Osteoclasts
Joint erosion
Bone destruction
TNFa IL-1
Synoviocytes
Macrophage
CD4 T lymphocyte
Cartilage destruction
Joint-space narrowing
TNFa IL-1
Chondrocytes
Adhesion molecule expression
Endothelial cell
Adapted from Arend WP.  J Rheumatol Suppl.
20026516-21. Permission to reproduce granted
by Journal of Rheumatology and Dr WP Arend.
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Cytokine Disequilibrium in the Disease Process
of RA1,2
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The Role of TNF
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TNF A Logical Target

• Helps drive events in the inflammatory cascade1-3
• Triggers production of other cytokines, including
  IL-11,2

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Three Destructive Effects of TNF1-5
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Summary

• RA is the most common inflammatory arthritis
• causes severe joint destruction
• is a systemic disease with systemic damage
• leads to disability
• Is associated with significant costs
• Is an immune mediated disease driven by
  inflammatory cytokines

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Managing RA Therapeutic Goals

• Control symptoms
• Minimize loss of function
• Reduce progression of disease

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Burden of Rheumatoid Arthritis

• Almost all patients have daily pain and
  functional loss
• Over time disease leads to structural damage and
  premature mortality
• RA patients have lower QOL than patients with
  other chronic diseases
• Collateral damage - CV, bone etc

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• Additional Slides

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TNF A Logical Target

• TNF is involved in the disease process of
  Rheumatoid Arthritis (RA) at multiple
  levels3-7,9,10
• Activates immune cells, promoting an inflammatory
  response
• Binds to chondrocytes and osteoclasts, triggering
  multiple destructive effects
• Induces expression of adhesion molecules,
  promoting the migration of T cells into the
  synovium
• Stimulates production of other proinflammatory
  cytokines
• With these effects, TNF is a logical target for
  therapeutic intervention

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Two Approaches to TNF Inhibition1-5
Soluble Receptor
Anti-TNF Monoclonal Antibodies (MAbs)
Etanercept (human soluble receptor)
Infliximab (chimeric MAb)
Murine region (binding site for TNF)
Human (IgG1)
Adalimumab (human MAb)
Fc regionof humanIgG1
Extracellular domain of human p75 TNF receptor
(binding site for TNF)
Human (IgG1)
Human variable region (binding site for TNF)
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Medicine and Health

• Demand for health care and medicines is a derived
  demand for improved health
• Two sources of value
• Health as an input to production
• Health as an input to consumption
• Medicine offers opportunities for investing in
  improved health

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Utility and Health Status
Sweden
UK
Kobelt G et al. Arthritis Rheum. 2002462310-9.
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How is Value Measured?

• Cost consequence analysis
• Costs and outcomes presented
• Cost minimisation analysis
• Costs compared, outcomes equivalent
• Cost effectiveness analysis
• Costs and clinical outcome presented
• Cost utility analysis
• Costs in monetary units, outcomes in Quality
  Adjusted Life Years
• Cost benefit analysis
• Costs and outcomes presented in monetary terms

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Workforce Participation at Different Levels of RA
Severity
of Patients below 66 working (Sweden 2002)
80
60
40
20
0
HAQ Groups
0-0.5
0.5-1.0
1.0-1.5
1.5-2.0
2.0-3.0
Mean age
52
52
54
52
57
Kobelt G et al, Rheumatology 2005441169-75.
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Treatment Costs for RA Annual cost per
patient treated

• Old drugs
• Methotrexate
• Introduced 1950s
• 400
• High value and affordability
• Do not work for all patients

• New drugs
• Anti-TNFs
• 15-20 000
• High value
• Affordability a problem
• Optimal treatment strategies must be designed

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Value and Ability to Pay

• The demand for health is determined by income and
  price
• Third party payment will not eliminate the
  scarcity of resources for medicines and
  improvements in health
• Why cannot third party payers price discriminate?
• Based on the assumption that markets can be kept
  separated

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Outcome and Cost-Effectiveness

• Summary
• Cost-.effectiveness studies have been widely used
  for decisions on resource allocation in RA
• Methodology for economic assessment in RA well
  developed
• QALY as outcome measure universally accepted
• Modeling progression and changes in costs and
  utilities with treatment over long term
• Models can only represent the underlying data
• Clinical trial population, costs, utilities
• Results can in addition differ due to
• Perspective chosen, time horizon, country
• WIth the exception of NICE models,
  cost-effectiveness ratios range between
  20-50,000 for the type of patient included in
  the clinical studies modeled
• Registry data will to some extent allow verifying
  modeling results