Ankylosing spondylitis

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Ankylosing spondylitis

• Dr Chris Edwards

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Prevalence
3

• Worldwide prevalence up to 0.91
• Prevalence varies by population and is closely
  correlated to prevalence of HLA-B272
• Prevalence also varies among ethnic groups
• MaleFemale 51
• Peak age of onset 15 35 years

1. Braun et al. Arthritis Rheum 1998 41 58-67.
2. Sieper J et al. Ann Rheum Dis 2002 61
(Suppl. III) iii8-18.
4
Co-morbidity co-mortality
5

• There may also be extra-articular manifestations
  of AS.
• Spinal fracture - most serious complication
  encountered in AS
• Prostatitis is prevalent among men with AS
• Long-term disease increases risk of
  cardiovascular complications
• Acute anterior uveitis occurs in 20 to 40 of
  cases. Other extra-articular manifestations
  include aortic regurgitation, pulmonary fibrosis,
  and, among male patients, prostatitis

Sieper J et al. Ann Rheum Dis 2002 61 (Suppl.
III) iii8-18.
6
Disease burden cost impact
7

• Etanercept provides a rapid reduction in
• disease activity
• Objective functional measures
• Work instability
• This suggests that therapy may be cost effective
  in terms of work disability

Barkham N et al Ann Rheum Dis 2008 67 (suppl II)
382
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Productivity Costs of ankylosing spondylitis in
the USA, The Netherlands, France and Belgium
USA (n241) Netherlands (n130) France (n 53) Belgium (n 26)
Work disability () 12 41 23 9
Days sick leave pt/y mean (range) Not stated 19 (0130) 6 (077) 9 (060)
Friction costs/pt/y mean (range) Not applied 1257 (07356) 428 (05979) 476 (02354)
Human capital costs/pt/y mean (range) US 4945 (045800) 4227 (039145) 8862 (046818) 3188 (043550) 3609 (034320)
Adjusted for age and sex. Includes patients with
partial work disability who continue in a
part-time paid job in The Netherlands and France
in those with a paid job converted to Euros
using 1998 purchasing power parities
Sieper J et al. Ann Rheum Dis 2002 61 (Suppl.
III) iii8-18.
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Disease burden quality of life impact
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Understanding the burden of disease
Quality of Life An individuals perception of
their position in the context of the culture and
value systems in which they live and in relation
to their
goals, expectations, standards and
concerns World Health Organisation (1995)
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Quality of Life

• Physical function
• ADL, mobility, physical activity
• Symptoms
• Pain, sleep, stiffness, fatigue
• Global health
• Social well-being
• Relationships, opportunities, sexual activity and
  satisfaction

• Role activities
• Employment, household management
• Emotional well-being
• Anxiety, control, self-esteem
• Cognitive function
• Cognition, concentration, memory
• Personal constructs
• Life satisfaction, stigma,
• Bodily appearance, spirituality

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Work disability AS-specific

• Employment rates range 5585
• 50 of studies report lt 70
• Work disability rates range 341
• 50 of studies report gt 20
• Risk factors
• Age
• Disease duration
• Physical function
• Pain
• Physically demanding jobs
• Lower education level

Sieper et al, 2002 Boonen et al, 2001
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Work disability AS-specific

• Workforce withdrawal
• 1st year 5
• 5 years 13
• 10 years 21
• 15 years 23
• 20 years 31
• 3.1x higher than general population

Sieper et al, 2002 Boonen et al, 2001
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Social well-being

• Older studies suggest few problems
• Intimate relationships
• Men no problems women less enjoyment
  (Elst et al, 1984)
• Few report marital strain / avoidance (Dalyan
  et al, 1999)
• 27 mild discomfort 7 severe discomfort
  (Wordsworth et al, 1986)
• Impact on daily life (n 129) - reporting
  limitations
• 1 social interactions
• 2 communication
• 3 normal role activities
• 6 leisure activities

(Bakker et al, 1995)
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Social well-being AS and RA

• Health status comparison SF-36 generic health
  status
• AS better Physical health
• RA better Mental health
• No group differences for
• SF-36 Pain, Physical or Emotional-Role
  functioning,
  Social Function, Vitality or General Health
• Fatigue (MFI) or Behavioural Coping (CORS)
• Work ve association with physical health in
  both groups

Chorus et al, 2003
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SF-36 scores for patients with RA and patients
with AS
100
80
RA male
60
AS male
RA female
40
AS female
20
0
Physical Component
Mental Component
Summary
Summary
Chorus et al, 2003
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Immunology and pathogenesis
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Pathogenesis

• Immune-mediated, involving
• HLA-B27
• Inflammatory cellular infiltrates
• Cytokines such as TNFa and IL-10
• Genetic and environmental factors

Sieper J et al. Ann Rheum Dis 2002 61 (Suppl.
III) iii8-18.
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Diagnosis
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AS/SpA Characteristic Parameters Used for Early
Diagnosis
Inflammatory Back Pain
Symptoms
Imaging
Lab
ESR/CRP
HLA-B27
Patients history
Good response to NSAIDs
Family history
Rudwaleit M, et al. Ann Rheum Dis. 200463535-43
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AS/Axial SpA Typical Manifestations/Features
Sensitivity Specificity LR LR-
Inflammatory back pain 75 76 3.1 0.33
Enthesitis (heel pain) 37 89 3.4
Peripheral arthritis 40 90 4.0
Dactylitis 18 96 4.5
Anterior uveitis 22 97 7.3
Positive family history for SpA 32 95 6.4 0.29
Psoriasis 10 97 3.3
Inflammatory bowel disease 4 99 4.0
Good response to NSAIDs 77 85 5.1 0.27
Elevated acute phase reactants 50 80 2.5
HLA-B27 (axial involvement) 90 90 9.0 0.11
MRI (STIR) 90 90 9.0 0.11
Positive likelihood ratio (LR)
sensitivity/(100-specificity) Negative likelihood
ratio (LR-) (100-sensitivity/specificity)
Rudwaleit M, et al. Ann Rheum Dis.
200463535-43 Rudwaleit M, Feldtkeller E. and
Sieper J. Ann Rheum Dis 2007. In press.
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Spondyloarthritis - main manifestations

1. Axial involvement/spinal inflammation
2. Peripheral arthritis
3. Peripheral enthesitis

Axial SpA
SpA subtypes

1. Ankylosing spondylitis (AS)
2. Undifferentiated SpA
3. Psoriatic SpA
4. Reactive SpA
5. SpA associated with chronic inflammatory bowel
   diseases

AS
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Ankylosing Spondylitis a chronic inflammatory
rheumatic disease with debilitating potential

• main affection of the spine, entheses, peripheral
  joints and the eye
• main symptom inflammatory back pain
• 1/3 of patients with severe disease
• overall prevalence high (0.5)
• etiology unknown
• definite genetic load (new genes !)
• strong HLA B27 association
• late diagnosis (5-7 years)
• reduced quality of life
• increased risk of unemployment
• direct/indirect costs

24 years
AS
49 years
Zink A et al, J Rheum 2000, 2001 Boonen A et
al., Ann Rheum Dis 2001, 2002, Ward M et al. J
Rheum 2001, AR 2002
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Possible Outcomes of Ankylosing Spondylitis
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Age at Onset of Symptoms andAge at Diagnosis in
AS (DVMB)
Time from first symptoms to diagnosis 510 yrs
100
Age at onset of symptoms
80
Age at diagnosis
60
Patients ()
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n1396
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920 males 476 females
Age (yrs)
0
0
10
20
30
40
50
60
70
Feldtkeller E, et al. Z Rheumatol.
19995821-30. Feldtkeller E, et al. Rheumatol
Int. 20032361-6.
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Differentiating clinical features of IBP in
patients lt 45 years with chronic back pain
( gt 3 months )

• Morning stiffness gt 30 min
• Improvement with exercise, not with rest
• Awakening at 2. half of the night because of
  pain
• Alternating buttock pain

Diagnosis of IBP if 2 / 4 criteria are fulfilled
sensitivity 70 specificity 81
(AS n 101 non-AS back pain n 112)
Rudwaleit M et al. AR 2006
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Use of the new IBP criteria as diagnostic
criteria in individual patients

• Morning stifness gt 30 min
• Improvement by movement, but not rest
• Wakening up in the 2nd half of the night
  because of pain
• Alternating buttock pain

2 out of 4 positive
Sensitivity 70.3
Specificity 81.2
LR 3.7
3 out of 4 positive
Sensitivity 33.6
Specificity 97.3
LR 12.4
Rudwaleit et al. Arthritis Rheum 200654678-81
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X-ray evidence of sacroiliitis a prerequisite
for diagnosing AS (modified NY criteria 1984)
van der Linden Arthritis Rheum 1984
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A role for magnetic resonance imaging in the
diagnosis of early sacroiliitis in
pondyloarthritides
T2
T1
Active sacroiliac inflammation
Braun J et al. AR 1994
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The diagnostic value of scintigraphy in assessing
sacroiliitis in AS - a systematic literature
research

• Out of a total of 99 articles about scintigraphy
  found, 25 were included into the analysis.
• Overall sensitivity for scintigraphy to detect
  sacroiliitis was 52 for patients with
  established AS (N 361) and 49 for patients
  with probable sacroiliitis (N 255).
• Sensitivity of scintigraphy in AS patients with
  inflammatory back pain (indicating ongoing
  inflammation) was 53 (N 112) and in patients
  with AS and suspected sacroiliitis with magnetic
  resonance imaging showing acute sacroiliitis (as
  a gold standard) was 53 (N62).
• In controls with MLBP specificity was 78 (N
  60), resulting in LRs not higher than 2.5-3.0.
• The data suggest that scintigraphy of the
  sacroiliac joints is at the most of limited
  diagnostic value for the diagnosis of established
  AS including the early diagnosis of probable /
  suspected sacroiliitis.

Song I et al. Ann Rheum Dis. 2008 Jan 29 Epub
ahead of print
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Early back pain cohort clinical items vs.
imaging for the diagnosis of spondyloarthritis
n 69 with IBP lt 2 years
Heuft-Dorenbosch L et al. Ann Rheum Dis. 2006
Jun65(6)804-8. Epub 2005 Oct 11
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What is helpful for an early diagnosis of AS ?

• Screen young patients ( lt 45 y) with back pain gt
  3 months
• Ask for inflammatory back pain
• Ask for other signs of spondyloarthritis
  (uveitis, enthesitis)
• Do the HLA B27 test
• Add imaging when necessary (MRI, X-rays)

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AS assessment tools
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AS Measures of Disease Outcome

• Bath Ankylosing Spondylitis (BAS) scales
• BASDAI Disease Activity Index
• BASFI Functional Index
• BASGI Global Index
• BASMI Metrology Index
• BASRI Radiographic Index
• Other measurement indexes
• SF-36 36-Item Medical Outcomes Study Short-Form
  Health Survey
• ASAS Assessments in Ankylosing Spondylitis
  Working Group Improvement Criteria

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Disease Activity Assessment
Index Metric
BASFI Disability Level
BASDAI Disease Activity Level
BASMI Spinal Mobility
ASAS - IC Composite Sum of Disease Activity
BASFI Bath Ankylosing Spondylitis Functional
Index BASDAI Bath Ankylosing Spondylitis
Disease Activity Index BASMI Bath Ankylosing
Spondylitis Metrology Index ASAS - IC
ASsessment in Ankylosing Spondylitis Improvement
Criteria
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Bath Ankylosing Spondylitis Functional Index
(BASFI)

• Visual analogue scale
• Easy (1) impossible (10)
• Mean (VAS) of 10 questions
• Putting on your socks or tights without help or
  aids
• Bending forward from the waist to pick up a pen
  from the floor without an aid
• Reaching up to a high shelf without help or aids
  (e.g helping hand)
• Getting up out of an armless dining room chair
  without using your hands or other help
• Getting up off the floor without help from lying
  on your back
• Standing unsupported for ten minutes without
  discomfort?
• Climbing 12-15 steps without using a handrail or
  walking aid (one foot on each step)?
• Looking over your shoulder without turning your
  body?
• Doing physically demanding activities (eg physio
  exercises, gardening, sport)?
• Doing a full days activities at home or at work?

relate to the functional anatomy of subjects
relate to a subjects ability to cope with
everyday life
Calin, J Rheumatol 1994212281-85.
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Bath Ankylosing Spondylitis Disease Activity
Index (BASDAI)

• Visual analogue scale (0 10 cm)
• None (1) Very severe (10)
• Fatigue - How would you describe the overall
  level of fatigue/tiredness you have experienced?
• Spinal pain - How would you describe the overall
  level of AS neck, back or hip pain you have had?
• Joint pain - How would you describe the overall
  level of pain/swelling in joints other than neck,
  back or hips you have had?
• Enthesitis - How would you describe the overall
  level of discomfort you have had from any areas
  tender to touch or pressure?
• Inflammation
• Duration morning stiffness - How would you
  describe the overall level of morning stiffness
  you have had from the time you wake up?
• Severity morning stiffness - How long does your
  morning stiffness last from the time you wake up?
  (scale of 0 to gt2 hrs)
• BASDAI
• 0.2 F S J E 0.5 (Duration Severity
  Morning Stiffness)
• Range 0 10

Garrett, J Rheumatol 1994212286-91.
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Bath Ankylosing Spondylitis Metrology Index
(BASMI)

• Represented as aggregate score (ranging from 0 to
  10) using the variables below

Score Score Score
Measurement 0 1 2
Tragus-to-wall lt 15 cm 15 to 30 cm gt30 cm
Lumbar flexion (modified Schober test) gt 4 cm 2 to 4 cm lt 4 cm
Cervical rotation gt 70º 20 to 70º lt 20º
Lumbar side flexion gt 10 cm 5 to 10 cm lt 5 cm
Intermalleolar distance gt 100 cm 70 to 100 cm lt 70 cm
Jenkinson, J Rheumatol 1994211694-98.
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Objectives of disease management

• Reduce and/or prevent deleterious effects of
• Inflammation
• Ankylosis
• Abnormal posture
• Aim for
• No or low disease activity (pain, stiffness, MRI,
  CRP)
• Good function, no disability
• No structural damage (no growth of
  syndesmophytes)
• Good quality of life
• No increased cardiovascular morbidity
• Normal life expectancy

Dougados M et al. J.Rheumatol 200128-6216-20