Out Come Of R

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RA Outcomes RA Outcomes King’s College Hospital King’s College Hospital

Transcript of Out Come Of R

  • 1.RA Outcomes Kings College Hospital

2. RA Outcomes

  • Damage
  • Disability
  • Death

3. Summary Of Presentation

  • Disease Activity and Outcomes
  • Clinical measures
  • Combined measures
  • Functional measures
  • Radiological assessments
  • Mortality

4. Relationships of RA Outcomes Disability Pain Damage 5. Specific Factors Related toPoor Outcome in RA

  • Severe disease
    • many involved joints
    • RF positivity
    • high ESR/CRP
    • rheumatoid nodules
  • Additional factors
    • slow onset
    • late presentation
    • old age
    • female
    • many comorbidities
    • poverty

6. Disease Activity States

  • RA symptoms come and go
    • Depending on inflammation
  • When tissues are inflamed
    • RAis active
  • When tissue inflammation subsides
    • RAis inactive (in remission)
  • High disease activity
    • More drugs needed
  • Reduced disease activity
    • Treatment successful
  • Low disease activity
    • Treatment sufficient
  • Problems
  • Physicians vary
  • Patients vary
  • Physicians and patients disagree

7. Assessing Disease Activity

  • Core Data Set
  • Swollen joints
  • Tender joints
  • Pain
  • Global Assessment
  • ESR/CRP
  • HAQ
  • X-rays
  • Combining Data
  • ACR Responders
  • DAS

8. Treatment Goals With Anti-Rheumatic Drugs Inflammation Disability Radiographs Severity(arbitrary units) Durationof Disease (years) Early 0 5 10 15 20 25 30 ACR Intermediate Late

  • Overall Aims
  • Reduce disease severity
  • Improve disability
  • Stop joint damage
  • Avoid major adverse events

9. Clinical Measures Swollen and Tender Joint Counts 28 Joint Index 66 Joint Index 10. Joint Counts in 503 RA patients Swollen Joints Tender Joints 11. Visual Analogue Pain Scores

  • Advantages
    • Simple
    • Understandable
    • Rapidly recorded
    • Conventional
  • Limitations
    • Irrelevant
    • Variable
    • Subjective
    • Inaccurate

None Worst Assessment 12. VAS Scores And Laboratory Measures VAS Pain VAS Patient Global ESR

  • Patient measures on VAS differ from joint counts
  • They also differ from ESR and C-reactive protein
  • Flatter distribution

13. Correlations of Clinical Measures

  • Tender Swollen Patient Pain
  • Joints Joints Global
  • ESR 0.14 0.25 0.24 0.21
  • Pain 0.47 0.36 0.83
  • Patient Global 0.48 0.34
  • Swollen joints 0.51

14. Combining Measures

  • Indices
  • 1977 Smyth - A pooled index
  • 1981 Mallya - Index of disease activity
  • 1990 Davis - Stoke index
  • 1990 Van der Heijde - Disease Activity Score
  • 1995 Symmons -Overall Status (OSRA)
  • 1995 Prevoo - Modified DAS (28-joint counts )
  • Response Criteria
  • American College of Rheumatology
  • Combine joint counts, patient/physician global assessments, pain, ESR and HAQ.
  • 20%, 50% or 70% responses

15. Changes in DAS with TNF From Professor Piet Van Riel 16. Listening to Patients Self-Assessment can replace clinician assessment

  • Patient-based disease activity score (PDAS)
    • Accurate
    • Reproducible
    • Valid
  • Equivalent to clinician assessments (DAS)

17. What is functional outcome? Disability and Health Status

  • Focus on subjective assessments
    • Questionnaires rather than direct measures
  • HAQ dominates
    • Good for groups, poor for individuals
    • Rarely used in routine practice
  • Many alternative health status measures
    • SF-36, Nottingham Health Profile, EuroQol
    • Some agreement, but important differences
    • Not interchangeable

18. Measuring DisabilityMeasuring Instruments

  • Disease specific
    • Health Assessment Questionnaire (HAQ)
    • Arthritis Impact Measurement Scale (AIMS)
  • Generic
    • Medical Outcome Study SF-36
    • Nottingham Health Profile (NHP)

19. Health Assessment Questionnaire Fries Contributionto Rheumatology 20. Components of HAQ Scores Results in 103 RA patients 21. Progression of HAQ Scores Four Key Studiesin Early RA Five Key Studies in Established RA 22. Annual Change in the HAQ 25 cases followedfor 5 yearsin London 105 cases followedfor 12 years in Holland 3 2 1 0 3 6 9 12 Disease Duration in Years HAQScore 23. Annual Increase of HAQ in Routine Practice Graphical Report of 13 studies 24. Limitations of Conventional Assessments Physician-measurement gives high placebo response

  • 1817 patients in trials
  • Physician-measurement (swollen joints)
    • high effect sizes with placebo
  • Patient-measurement (HAQ)
    • Low effect sizes with placebo

Scott and Strand, Rheumatology, 2002 25. Comparing HAQ with EuroQol Different distributions shown in 320 RA patients 26. Health Profiles in RA Nottingham Health Profile Nottingham Health Profile 27. Health Profiles in RA Nottingham Health Profile Nottingham Health Profile 28. HAQ scores over the course of RA Changing correlations with time Welsing et al, Arthritis Rheum, 2000

  • HAQ-DAS
  • Baseline 0.40
  • 6 years 0.79
  • 9 years -0.02
  • HAQ-Sharp Score
  • Baseline 0.15
  • 6 years 0.75
  • 9 years 0.57

Increases Over 10 Years Changing Correlations HAQ Score Months 29. HAQ and DMARDs 12 Months data from leflunomide database (US 301) LEFLUN PL MTX 0.10 0.00 -0.10 -0.20 -0.30 Improvement 1 3 6 9 12 Change in HAQ score Months 30. HAQ And DMARDs 6 month individual changes in HAQ from leflunomide trial (MN 301) 31. HAQ and DMARDsAll phase III leflunomide trials (ITT analysis) 32. HAQ and DMARDsSustained changes in HAQ during 2 years leflunomide HAQ Scores MN 305(60 cases) MN 304(248 cases) US 301(97 cases) 33. Steroid/DMARD combinations in Early RA ARC (Kirwan) and Cobra studies ARC Cobra 34. Steroid/DMARD combinations in Late RA Adding IM Depomedrone to DMARDs Choy et al, Ann Rheum Dis, 2005

  • 91 RA patients on DMARDs
    • Partial responders
  • Randomised to receive
    • IM Depomedrone
    • Placebo
  • Followed for 24 months
  • HAQ scores
    • Minor short term improvements with steroids

35. DMARD CombinationsAdding leflunomide to MethotrexateKremer et al, J Rheum, 2004

  • RA patients active despiteadequate MTX therapy
  • 263 randomised patients
    • 6 month RCT
    • 6 month extension
  • First 6 months
    • Methotrexate/leflunomide
    • Methotrexate/Placebo
  • Second 6 months
    • Methotrexate/leflunomide

36. DMARD combinations in Early RA FinRA-Co and MTX/SZP ( Maillefert)studies FinRA-Co MTX/SZP 37. HAQ and Anti-TNF 3-year enbrel therapy in 671 patients Baumgartner et al, J Rheum, 2004 0 6 12 18 24 30 36 0.8 1.2 1.6 0.4 HAQ Scores Months Early Established 38. Anti-TNF and HAQ Systematic Review for NICE appraisal Moreland Wadjula Weinblatt Etanercept Attract Infliximab All trials -1.0 -0.5 0 0.5 1.0 Favours treatment Favours control 39. Comparative Changes in HAQ Leflunomide versus Anti-TNF 40. Percent Changes In HAQ RCTs for registration of new DMARDs/biologics After Vibeke Strand 41. Measuring Quality of Life Improves Assessments of Anti-TNF

  • 20 RA patients
  • Treated with infliximab
  • Assessed at3 months
  • RA QoL shows improvements

Treatment Baseline RAQol Score 30 20 10 0 42. Aggressive DMARD regimens Aggressive/Standard DMARDs Late RABROSG Study Early DMARDs/pyramidal NSAIDs Early RA Utrecht Arthritis Cohort Study HAQ 43. Intensive versus routine treatmentTICORA trial in early RA Grigor et al, Lancet, 2004

  • Single-blind RCT
    • 111 RA patients
    • in Glasgow
  • Randomised to receive:
    • intensive management
    • routine care
  • ITT analysis
    • HAQ secondary outcome

44. Explaining Relationships of HAQ Joint damage act as regulatorSets disability level in which day-to-day variation occurs Synovitis Joint damage Disability 45. MeasuringDamage From normality to failed joints 46. Some X-ray Scoring Systems

  • Year Authors Main features
  • 1949 Steinbrocker 0-4 grading using standardised ARA criteria
  • 1961 ERC gold study Separate erosion/joint space narrowing scores
  • 1963 Kellgren Standard reference films
  • 1969 Berens & Lin Global scale from 0 to 5
  • 1971 Sharp Erosion/oint space narrowing scores for hands
  • 1976 Trentham & Masi Carpo-metacarpal ratio
  • 1977 Amos Counting new erosions in hands and wrists
  • 1977 Larsen Global score with standard reference films
  • 1983 Genant Erosion/joint space narrowing scores with standard X-rays
  • 1983 Bluhm Erosion/joint space narrowing scores with standard X-rays
  • 1985 Scott Erosion/joint space narrowing/malalignment/total scores
  • 1987 Kaye Erosion/joint space narrowing/malalignment/total scores
  • 1989 Van der Heijde Modified Sharp index including feet

47. Changes in Larsen Score in Early RA Average of two observers

  • Correlations
  • Initial Final Change
  • Pearson0.87 0.93 0.70
  • Spearman 0.86 0.80 0.60

48. X-ray Progression Studies using Sharp and Larsen Scores Single Centre Cross-Sectional Study Longitudinal Studies From 8 centres 49. Correlating Damage WithDisability 5 studies in early RA and 8 in late RA

  • Study Year Cases Durn Correl Signif
  • Eberhardt 1995 63 Early 0.27 NS
  • van Leeuwen 1994 149 Early 0.31 P