Ankylosing spondylitis

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Presentation transcript:

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

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) Health: is a complete state of physical, mental, and social well-being and not merely the absence of disease or infirmity World Health Organisation (1947) BoD in AS – less well understood than RA – but in recent years increase in our understanding To measure health we need to define it. Quality of Life – no consensus on definition - generally an inclusive approach to health is recommended – including physical, emotional and social well-being. Most widely cited definition – recently developed further with the International Classification of Disease – provides a comprehensive framework for considering the consequences of health and disease. Definition recognises health as multi-dimensional; recognises the positive and negative aspects of health. The definition has informed a number of instruments.

Quality of Life Physical function Symptoms Global health 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 QoL influenced by main disease disability pathways and factors external to this pathway – eg educatin and psychosocial characteristics List: domains of health most commonly identified in the literature as relevant to PROMs. Range from those most obviously related to a patient’s health status – global view, symptoms, emotional wb to tose reflecting a broader view of health / life – social function, role activity. Some domains poorly explored in literature – such as body impact, sense of embarrassment or stigma associated with some health problems. When list from UK survey grouped: Role activities – 1 Symptoms – 4 Personal construct – 2 Physical function – 7 Emotional wb – 3 Social wb - 7

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 WD in AS can often be masked – but increasing evidence that AS influences career decisions. AS-specific Employment rates range 55-85% 50% of studies report rates < 70% Work disability rates range 3-41% 50% of studies report rates > 20% Higher employment rates for AS v RA. – see also compared to other rheum conditions But much lower than general pop (but not for women?) Workforce Withdrawal (Boonen 2001) Yearly increase: 5% first year 13% 5yrs 21% 10yrs 23% 15yrs 31% 20yrs Age and sex adjusted risk of withdrawal 3.1x higher than general Dutch pop. ick Risk factor – include: older age at diagnosis; manual work; coping strategies Psychosocial impact of Work Disability Majority –ve views Frustration, inadequacy, reduced choice, dependency, reduced self-esteem Few +ve views Positive mood, less pressured, ‘life has new meaning’ 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 WD in AS can often be masked – but increasing evidence that AS influences career decisions. AS-specific Employment rates range 55-85% 50% of studies report rates < 70% Work disability rates range 3-41% 50% of studies report rates > 20% Higher employment rates for AS v RA. – see also compared to other rheum conditions But much lower than general pop (but not for women?) Workforce Withdrawal (Boonen 2001) Yearly increase: 5% first year 13% 5yrs 21% 10yrs 23% 15yrs 31% 20yrs Age and sex adjusted risk of withdrawal 3.1x higher than general Dutch pop. ick Risk factor – include: older age at diagnosis; manual work; coping strategies Psychosocial impact of Work Disability Majority –ve views Frustration, inadequacy, reduced choice, dependency, reduced self-esteem Few +ve views Positive mood, less pressured, ‘life has new meaning’ Sieper et al, 2002; Boonen et al, 2001

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 Little research Bakker – impact on daily routine activities (n= 129) – few reported difficulties with social function: 6% leisure, 3% role activities, 2% communication, 1% social interaction. Sexual health Wordsworth (survey of n=100) (Bakker et al, 1995)

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 No studies comparing impact of AS directly to general population??? – but numerous comparing RA and GP Norm based scoring of SF-36 – supports interpretation MFI Multidimensional Fatigue Inventory CORS Coping with Rheumatic Stressors Chorus et al, 2003

SF-36 scores for patients with RA and patients with AS 100 80 RA male 60 AS male 40 RA female Comparison between RA and AS patients SF-36 generic health status AS better Physical health RA better Mental health No group differences for: Pain, Physical or Emotional-Role functioning, Social Function, Vitality or General Health (all SF-36) Fatigue (MFI) or Behavioural Coping (CORS) Work: +ve association with physical health in both groups 20 AS female Physical Component Mental Component Summary Summary Chorus et al, 2003

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

AS/SpA: Characteristic Parameters Used for Early Diagnosis Symptoms Inflammatory Back Pain Imaging Lab HLA-B27 ESR/CRP Patient’s history Good response to NSAIDs Family history Rudwaleit M, et al. Ann Rheum Dis. 2004;63:535-43

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% 3.3 Inflammatory bowel disease 4% 99% Good response to NSAIDs 77% 85% 5.1 0.27 Elevated acute phase reactants 50% 80% 2.5 HLA-B27 (axial involvement) 9.0 0.11 MRI (STIR) Positive likelihood ratio (LR+) = sensitivity/(100-specificity) Negative likelihood ratio (LR-) = (100-sensitivity/specificity) Rudwaleit M, et al. Ann Rheum Dis. 2004;63:535-43 Rudwaleit M, Feldtkeller E. and Sieper J. Ann Rheum Dis 2007;. In press.

Spondyloarthritis - main manifestations Axial involvement/spinal inflammation Peripheral arthritis Peripheral enthesitis Axial SpA SpA subtypes Ankylosing spondylitis (AS) Undifferentiated SpA Psoriatic SpA Reactive SpA SpA associated with chronic inflammatory bowel diseases AS

Ankylosing Spondylitis: a chronic inflammatory rheumatic disease with debilitating potential 24 years 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 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, A&R 2002

Possible Outcomes of Ankylosing Spondylitis

Age at Onset of Symptoms and Age at Diagnosis in AS (DVMB) Time from first symptoms to diagnosis: 5–10 yrs 100 Age at onset of symptoms 80 Age at diagnosis 60 Patients (%) 40 n=1396 20 920 males 476 females Age (yrs) 10 20 30 40 50 60 70 Feldtkeller E, et al. Z Rheumatol. 1999;58:21-30. Feldtkeller E, et al. Rheumatol Int. 2003;23:61-6.

Diagnosis of IBP if 2 / 4 criteria are fulfilled Differentiating clinical features of IBP in patients < 45 years with chronic back pain ( > 3 months ) 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 sensitivity 70 % specificity 81 % (AS n = 101; non-AS back pain n = 112) Rudwaleit M et al. A&R 2006

Use of the new IBP criteria as diagnostic criteria in individual patients 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 ≥ 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 2006;54:678-81

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 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 Early back pain cohort: clinical items vs. imaging for the diagnosis of spondyloarthritis n = 69 with IBP < 2 years Heuft-Dorenbosch L et al. Ann Rheum Dis. 2006 Jun;65(6):804-8. Epub 2005 Oct 11

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

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

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 day’s activities at home or at work? relate to the functional anatomy of subjects relate to a subject’s ability to cope with everyday life Calin, J Rheumatol 1994;21:2281-85.

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 >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 1 2 Tragus-to-wall < 15 cm 15 to 30 cm >30 cm Lumbar flexion (modified Schober test) > 4 cm 2 to 4 cm < 4 cm Cervical rotation > 70º 20 to 70º < 20º Lumbar side flexion > 10 cm 5 to 10 cm < 5 cm Intermalleolar distance > 100 cm 70 to 100 cm < 70 cm Jenkinson, J Rheumatol 1994;21:1694-98.

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 2001;28-62:16-20