Ankylosing spondylitis

Dr Chris Edwards

Prevalence

• Worldwide prevalence up to 0.9%1

• Prevalence varies by population and is closely correlated to prevalence of HLA-B272

• Prevalence also varies among ethnic groups • Male:Female – 5:1• 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.

Co-morbidity & co-mortality

• 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.

Disease burden – cost impact

• 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

Productivity Costs of ankylosing spondylitis in the USA, The Netherlands, France and Belgium

USA (n=241) Netherlands (n=130)

France (n= 53) Belgium (n= 26)

Work disability (%)

12 41* 23* 9*

Days sick leave pt/y; † mean (range)

Not stated 19 (0–130) 6 (0–77) 9 (0–60)

Friction costs/pt/y: † mean (range)

Not applied €1257 (0–7356) €428 (0–5979) €476 (0–2354)

Human capital costs/pt/y; mean (range)

US $4945 (0–45800)€4227 (0–39145)‡

€8862 (0–46818)

€3188 (0–43550)

€3609 (0–34320)

*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.

Disease burden – quality of life impact

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)

Understanding the burden of disease

Quality of Life

• Physical functionADL, mobility, physical activity

• SymptomsPain, sleep, stiffness, fatigue

• Global health

• Social well-beingRelationships, opportunities, sexual activity and satisfaction

• Role activitiesEmployment, household management

• Emotional well-beingAnxiety, control, self-esteem

• Cognitive functionCognition, concentration, memory

• Personal constructsLife satisfaction, stigma,Bodily appearance, spirituality

Sieper et al, 2002; Boonen et al, 2001

Work disability: AS-specific

• Employment rates range 55–85%• 50% of studies report < 70%

• Work disability rates range 3–41%• 50% of studies report > 20%

• Risk factors: • Age• Disease duration• Physical function**• Pain• Physically demanding jobs• Lower education level

Sieper et al, 2002; Boonen et al, 2001

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

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)

Chorus et al, 2003

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

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Physical ComponentSummary

Mental ComponentSummary

RA male

AS male

RA female

AS female

Chorus et al, 2003

SF-36 scores for patients with RA and patients with AS

Immunology and pathogenesis

Pathogenesis

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

Sieper J et al. Ann Rheum Dis 2002; 61 (Suppl. III): iii8-18.

Diagnosis

Good responseto NSAIDs

SymptomsSymptoms

ImagingImaging

LabLab

Patient’sPatient’shistoryhistory

InflammatoryBack Pain

ESR/CRP

Rudwaleit M, et al. Ann Rheum Dis. 2004;63:535-43

HLA-B27

Family history

AS/SpA: Characteristic Parameters Used for Early Diagnosis

Positive likelihood ratio (LR+) = sensitivity/(100-specificity)Negative likelihood ratio (LR-) = (100-sensitivity/specificity)

Rudwaleit M, et al. Ann Rheum Dis. 2004;63:535-43Rudwaleit M, Feldtkeller E. and Sieper J. Ann Rheum Dis 2007;. In press.

Sensitivity Specificity LR+ LR-Inflammatory back pain 75% 76% 3.1 0.33Enthesitis (heel pain) 37% 89% 3.4Peripheral arthritis 40% 90% 4.0Dactylitis 18% 96% 4.5Anterior uveitis 22% 97% 7.3Positive family history for SpA 32% 95% 6.4 0.29Psoriasis 10% 97% 3.3Inflammatory bowel disease 4% 99% 4.0Good response to NSAIDs 77% 85% 5.1 0.27Elevated acute phase reactants

50% 80% 2.5

HLA-B27 (axial involvement) 90% 90% 9.0 0.11MRI (STIR) 90% 90% 9.0 0.11

AS/Axial SpA: Typical Manifestations/Features

Spondyloarthritis - main manifestations

1. Ankylosing spondylitis (AS)

2. Undifferentiated SpA

3. Psoriatic SpA

4. Reactive SpA

5. SpA associated with chronic inflammatory bowel diseases

AS

SpA subtypes

1. Axial involvement/spinal inflammation2. Peripheral arthritis3. Peripheral enthesitis

Axial SpA

Ankylosing Spondylitis: a chronic inflammatory rheumatic disease with debilitating potential

Zink A et al, J Rheum 2000, 2001; Boonen A et al., Ann Rheum Dis 2001, 2002, Ward M et al. J Rheum 2001, A&R 2002

• 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

49 years

AS

Possible Outcomes of Ankylosing Spondylitis

Feldtkeller E, et al. Z Rheumatol. 1999;58:21-30.Feldtkeller E, et al. Rheumatol Int. 2003;23:61-6.

Age at Onset of Symptoms andAge at Diagnosis in AS (DVMB)

80

Patie

nts

(%)

Age at onset ofsymptoms

Age at diagnosis

Age (yrs)

920 males476 females

n=1396

100

60

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00 10 20 30 40 50 60 70

Time from first symptoms to diagnosis: 5–10 yrs

Differentiating clinical features of IBP in patients < 45 years with chronic back pain

*

**

*

sensitivity 70 %specificity 81 %

• Morning stiffness > 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

Rudwaleit M et al. A&R 2006

(AS n = 101; non-AS back pain n = 112)

( > 3 months )

Use of the new IBP criteria as diagnostic criteria in individual patients

≥ 2 out of 4 positiveSensitivity 70.3%

Specificity 81.2%

LR+ 3.7

Rudwaleit et al. Arthritis Rheum 2006;54:678-81

• Morning stifness > 30 min

• Improvement by movement, but not rest

• Wakening up in the 2nd half of the night because of pain

• Alternating buttock pain

≥ 3 out of 4 positiveSensitivity 33.6%

Specificity 97.3%

LR+ 12.4

X-ray evidence of sacroiliitis: a prerequisite for diagnosing AS (modified NY criteria 1984)

van der Linden Arthritis Rheum 1984

A role for magnetic resonance imaging in the diagnosis of early sacroiliitis in pondyloarthritides

Active sacroiliac inflammation

T1 T2

Braun J et al. A&R 1994

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 % (N=62).

• 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]

Early back pain cohort: clinical items vs. imaging for the diagnosis of spondyloarthritis

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X-rays MRI ESSGcriteria

X-raysMRIESSG criteria

Heuft-Dorenbosch L et al. Ann Rheum Dis. 2006 Jun;65(6):804-8. Epub 2005 Oct 11

n = 69 with IBP < 2 years

What is helpful for an early diagnosis of AS ?

• Screen young patients ( < 45 y) with back pain > 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)

AS assessment tools

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

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

Disease Activity Assessment

Index Metric

BASFI Disability Level

BASDAI Disease Activity Level

BASMI Spinal Mobility

ASAS - IC Composite Sum of Disease Activity

Bath Ankylosing Spondylitis Functional Index (BASFI)

• Visual analogue scale• Easy (1) – impossible (10)

• Mean (VAS) of 10 questions: 1. Putting on your socks or tights without help or aids2. Bending forward from the waist to pick up a pen from the floor

without an aid3. Reaching up to a high shelf without help or aids (e.g helping

hand)4. Getting up out of an armless dining room chair without using

your hands or other help5. Getting up off the floor without help from lying on your back6. Standing unsupported for ten minutes without discomfort?7. Climbing 12-15 steps without using a handrail or walking aid

(one foot on each step)?8. Looking over your shoulder without turning your body?9. Doing physically demanding activities (eg physio exercises,

gardening, sport)?10. Doing a full day’s activities at home or at work?

Calin, J Rheumatol 1994;21:2281-85.

relate to the functional anatomy of subjects

relate to a subject’s ability to cope with everyday life

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

Visual analogue scale (0 – 10 cm)• None (1) – Very severe (10)1. Fatigue - How would you describe the overall level of fatigue/tiredness you have

experienced?2. Spinal pain - How would you describe the overall level of AS neck, back or hip pain you

have had? 3. Joint pain - How would you describe the overall level of pain/swelling in joints other than

neck, back or hips you have had?4. Enthesitis - How would you describe the overall level of discomfort you have had from

any areas tender to touch or pressure?5. Inflammation:

1. Duration morning stiffness - How would you describe the overall level of morning stiffness you have had from the time you wake up?

2. Severity morning stiffness - How long does your morning stiffness last from the time you wake up? (scale of 0 to >2 hrs)

BASDAI = 0.2 [F + S + J + E + 0.5 (Duration + Severity Morning Stiffness)]

• Range 0 – 10

Garrett, J Rheumatol 1994;21:2286-91.

Bath Ankylosing Spondylitis Metrology Index (BASMI)

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

Score

Measurement 0 1 2Tragus-to-wall < 15 cm 15 to 30 cm >30 cmLumbar flexion (modified Schober test)

> 4 cm 2 to 4 cm < 4 cm

Cervical rotation > 70º 20 to 70º < 20ºLumbar side flexion > 10 cm 5 to 10 cm < 5 cmIntermalleolar distance > 100 cm 70 to 100 cm < 70 cm

Jenkinson, J Rheumatol 1994;21:1694-98.

Dougados M et al. J.Rheumatol 2001;28-62:16-20

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