RA Outcomes King’s College Hospital
RA Outcomes <ul><li>Damage </li></ul><ul><li>Disability </li></ul><ul><li>Death </li></ul>
Summary Of Presentation <ul><li>“ Disease Activity” and Outcomes </li></ul><ul><li>Clinical measures </li></ul><ul><li>Com...
Relationships of RA Outcomes Disability Pain Damage
Specific Factors Related to  Poor Outcome in RA <ul><li>Severe disease </li></ul><ul><ul><li>many involved joints </li></u...
Disease Activity States <ul><li>RA symptoms come and go </li></ul><ul><ul><li>Depending on inflammation  </li></ul></ul><u...
Assessing Disease Activity <ul><li>Core Data Set </li></ul><ul><li>Swollen joints </li></ul><ul><li>Tender joints </li></u...
Treatment Goals With Anti-Rheumatic Drugs Inflammation Disability Radiographs Severity  (arbitrary units) Duration  of Dis...
Clinical Measures Swollen and Tender Joint Counts 28 Joint Index 66 Joint Index
Joint Counts in 503 RA patients Swollen Joints Tender Joints
Visual Analogue Pain Scores <ul><li>Advantages </li></ul><ul><ul><li>Simple </li></ul></ul><ul><ul><li>Understandable </li...
VAS Scores And Laboratory Measures VAS Pain VAS Patient Global ESR <ul><li>Patient measures on VAS differ from joint count...
Correlations of Clinical Measures <ul><li>Tender Swollen Patient Pain </li></ul><ul><li>Joints Joints Global </li></ul><ul...
Combining Measures <ul><li>Indices </li></ul><ul><li>1977 Smyth - A pooled index </li></ul><ul><li>1981 Mallya - Index of ...
Changes in DAS with TNF From Professor Piet Van Riel
Listening to Patients Self-Assessment can replace clinician assessment <ul><li>Patient-based disease activity score (PDAS)...
What is functional outcome? Disability and Health Status <ul><li>Focus on subjective assessments </li></ul><ul><ul><li>Que...
Measuring Disability  Measuring Instruments <ul><li>Disease specific </li></ul><ul><ul><li>Health Assessment Questionnaire...
Health Assessment Questionnaire Fries Contribution  to Rheumatology
Components of HAQ Scores Results in 103 RA patients
Progression of HAQ Scores Four Key Studies  in Early RA Five   Key   Studies in   Established   RA
Annual Change in the HAQ 25 cases followed  for 5 years  in London 105 cases followed  for 12 years in Holland 3 2 1 0 3 6...
Annual Increase of HAQ in Routine Practice Graphical Report of 13 studies
Limitations of Conventional Assessments Physician-measurement gives high placebo response <ul><li>1817 patients in trials ...
Comparing HAQ with EuroQol Different distributions shown in 320 RA patients
Health Profiles in RA Nottingham Health Profile Nottingham Health Profile
Health Profiles in RA Nottingham Health Profile Nottingham Health Profile
HAQ scores over the course of RA Changing correlations with time Welsing et al, Arthritis Rheum, 2000 <ul><li>HAQ-DAS   </...
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...
HAQ And DMARDs 6 month individual changes in HAQ from leflunomide trial (MN 301)
HAQ and DMARDs  All phase III leflunomide trials (ITT analysis)
HAQ and DMARDs  Sustained changes in HAQ during 2 years leflunomide HAQ Scores MN 305  (60 cases) MN 304  (248 cases) US 3...
Steroid/DMARD combinations in Early RA ARC (Kirwan) and Cobra studies ARC Cobra
Steroid/DMARD combinations in Late RA Adding IM Depomedrone to DMARDs Choy et al, Ann Rheum Dis, 2005 <ul><li>91 RA patien...
DMARD Combinations  Adding leflunomide to Methotrexate  Kremer et al, J Rheum, 2004 <ul><li>RA patients active despite  ad...
DMARD combinations in Early RA FinRA-Co and MTX/SZP ( Maillefert)  studies FinRA-Co MTX/SZP
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...
Anti-TNF and HAQ Systematic Review for NICE appraisal Moreland Wadjula Weinblatt Etanercept Attract Infliximab All trials ...
Comparative Changes in HAQ Leflunomide versus Anti-TNF
Percent Changes In HAQ RCTs for registration of new DMARDs/biologics After Vibeke Strand
Measuring Quality of Life Improves Assessments of Anti-TNF <ul><li>20 RA patients </li></ul><ul><li>Treated with inflixima...
Aggressive DMARD regimens Aggressive/Standard DMARDs Late RA  BROSG Study Early DMARDs/pyramidal NSAIDs Early RA Utrecht A...
Intensive versus routine treatment  TICORA trial in early RA Grigor et al, Lancet, 2004 <ul><li>Single-blind RCT </li></ul...
Explaining Relationships of HAQ Joint damage act as “regulator”  Sets disability level in which day-to-day variation occur...
Measuring  Damage From normality to failed joints
Some X-ray Scoring Systems <ul><li>Year Authors Main features </li></ul><ul><li>1949 Steinbrocker 0-4 grading using standa...
Changes in Larsen Score in Early RA Average of two observers <ul><li>Correlations </li></ul><ul><li>Initial Final Change <...
X-ray Progression Studies using Sharp and Larsen Scores Single Centre Cross-Sectional Study Longitudinal Studies From 8 ce...
Correlating Damage With  Disability 5 studies in early RA and 8 in late RA <ul><li>Study Year Cases Dur’n Correl Signif </...
Large Joint Damage And Disability Effect on HAQ score after 12 years RA <ul><li>Impact on Disability </li></ul><ul><li>Mul...
Digression on Steroids: Historical Perspective Major Breakthrough in RA Over 50 Years Ago Philip  Hench  Edward Kendall Ta...
New Role in 1990’s Combined with DMARDs  In Early RA to Prevent Erosions Approaches Constant Low Dose Tapering High Dose K...
IM Depomedrone In Established RA RCT Comparing 2-Years Monthly Depomedrone with Placebo in patients on DMARDs
The Popert Regimen  A Strong Belief in Combination Therapy <ul><li>Beliefs </li></ul><ul><li>Prolonged inpatient care need...
20 Year Results At Droitwich
RA Mortality  An Overview <ul><li>RA reduces the length of life </li></ul><ul><li>14 main studies since 1980 </li></ul><ul...
Cause-Specific Mortality RA Deaths In   20 Year Follow-up Study 9003 Scottish RA inpatients 1981-2000 Thomas et al, J Rheu...
Cause-Specific Mortality RA  SMR in   20 Year Follow-up Study 9003 Scottish RA inpatients 1981-2000 Thomas et al, J Rheuma...
Cardiovascular Mortality in Women RA 114 342 nurses without heart disease and RA in 1976  After 20 years: 527 had RA, 2296...
Mortality and Vascular Deaths RA, OA and No Arthritis From UK GP Database Women Men Watson et al, J Rheumatol, 2003
Deaths From Ischaemic Heart Disease SMR in 4 Studies of RA Patients
Deaths in Early Polyarthritis 1236 patients in NOAR Goodson et al, Arthritis Rheum, 2002
Cardiovascular Events In RA Unexplained by usual risk factors in 236 cases <ul><li>Predictor Rel Risk 95% CI </li></ul><ul...
Cardiovascular Risk Factors Comparison of OA and RA Dessein et al, Arthritis Research, 2002
Alternative Assessment of Risk Factors in RA
Joint Swelling And Cardiovascular Deaths Prospective Study of 4120 Pima Indians Jacobsson et al, Arthritis Rheum, 2001 Joi...
Predicting Mortality in RA 20 year study of 1381 Cases ESR Rheumatoid Factor Woolf et al, Arthritis Rheum, 2003 HAQ is ano...
Mortality With DMARDs Risks compared to no DMARDs 1240 RA patients and 191 deaths Choi et al, Lancet, 2002
Deaths With Methotrexate Reduced CVS Mortality Choi et al, Lancet, 2002
Deprivation Predicts Death in RA Long Term Results from Glasgow
The patient's journey with RA   Carol Simpson and Chloe Franks (patients) BMJ, October 2005
The patient's journey with RA   Carol Simpson and Chloe Franks (patients) BMJ, October 2005 <ul><li>Bad News </li></ul>Goo...
The patient's journey with RA   Carol Simpson and Chloe Franks (patients) BMJ, October 2005 <ul><li>Bad News </li></ul><ul...
Patient’s stories: Chloe <ul><li>“ I have tried a variety of treatments, including all the anti-TNF medications. Unfortuna...
Patients Stories: Carol <ul><li>“ My drug treatment for RA has not been at all successful... frequently the effect of the ...
Strengths and Weaknesses in Clinics Qualitative Research at Kings <ul><li>Good Features </li></ul><ul><li>Explained treatm...
<ul><li>Good Features </li></ul><ul><li>Explained treatments </li></ul><ul><li>Showed tests </li></ul><ul><li>Offered choi...
UK Standards of Care Arthritis and Musculoskeletal Alliance <ul><li>People have rights to: </li></ul><ul><li>Access to app...
UK Standards of Care Arthritis and Musculoskeletal Alliance <ul><li>Information and knowledge </li></ul><ul><li>Early diag...
Key Components of  ARMA Standards <ul><li>Information and knowledge </li></ul><ul><ul><li>Self-management guidance </li></...
Supporting People with  Long Term Conditions <ul><li>Linked NHS Programmes </li></ul><ul><li>Disease management </li></ul>...
Key Issue in UK Need for Early Treatment <ul><li>Early access to specialist advice </li></ul><ul><ul><li>Currently 3 month...
Key Points <ul><li>RA causes damage and disability </li></ul><ul><ul><li>both increase by about 1%/year </li></ul></ul><ul...
Upcoming SlideShare
Loading in …5
×

Out Come Of R

487 views
396 views

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
487
On SlideShare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
9
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Out Come Of R

  1. 1. RA Outcomes King’s College Hospital
  2. 2. RA Outcomes <ul><li>Damage </li></ul><ul><li>Disability </li></ul><ul><li>Death </li></ul>
  3. 3. Summary Of Presentation <ul><li>“ Disease Activity” and Outcomes </li></ul><ul><li>Clinical measures </li></ul><ul><li>Combined measures </li></ul><ul><li>Functional measures </li></ul><ul><li>Radiological assessments </li></ul><ul><li>Mortality </li></ul>
  4. 4. Relationships of RA Outcomes Disability Pain Damage
  5. 5. Specific Factors Related to Poor Outcome in RA <ul><li>Severe disease </li></ul><ul><ul><li>many involved joints </li></ul></ul><ul><ul><li>RF positivity </li></ul></ul><ul><ul><li>high ESR/CRP </li></ul></ul><ul><ul><li>rheumatoid nodules </li></ul></ul><ul><li>Additional factors </li></ul><ul><ul><li>slow onset </li></ul></ul><ul><ul><li>late presentation </li></ul></ul><ul><ul><li>old age </li></ul></ul><ul><ul><li>female </li></ul></ul><ul><ul><li>many comorbidities </li></ul></ul><ul><ul><li>poverty </li></ul></ul>
  6. 6. Disease Activity States <ul><li>RA symptoms come and go </li></ul><ul><ul><li>Depending on inflammation </li></ul></ul><ul><li>When tissues are inflamed </li></ul><ul><ul><li>RA is active </li></ul></ul><ul><li>When tissue inflammation subsides </li></ul><ul><ul><li>RA is inactive (in remission) </li></ul></ul><ul><li>High disease activity </li></ul><ul><ul><li>More drugs needed </li></ul></ul><ul><li>Reduced disease activity </li></ul><ul><ul><li>Treatment successful </li></ul></ul><ul><li>Low disease activity </li></ul><ul><ul><li>Treatment sufficient </li></ul></ul><ul><li>Problems </li></ul><ul><li>Physicians vary </li></ul><ul><li>Patients vary </li></ul><ul><li>Physicians and patients disagree </li></ul>
  7. 7. Assessing Disease Activity <ul><li>Core Data Set </li></ul><ul><li>Swollen joints </li></ul><ul><li>Tender joints </li></ul><ul><li>Pain </li></ul><ul><li>Global Assessment </li></ul><ul><li>ESR/CRP </li></ul><ul><li>HAQ </li></ul><ul><li>X-rays </li></ul><ul><li>Combining Data </li></ul><ul><li>ACR Responders </li></ul><ul><li>DAS </li></ul>
  8. 8. Treatment Goals With Anti-Rheumatic Drugs Inflammation Disability Radiographs Severity (arbitrary units) Duration of Disease (years) Early 0 5 10 15 20 25 30 © ACR Intermediate Late <ul><li>Overall Aims </li></ul><ul><li>Reduce disease severity </li></ul><ul><li>Improve disability </li></ul><ul><li>Stop joint damage </li></ul><ul><li>Avoid major adverse events </li></ul>
  9. 9. Clinical Measures Swollen and Tender Joint Counts 28 Joint Index 66 Joint Index
  10. 10. Joint Counts in 503 RA patients Swollen Joints Tender Joints
  11. 11. Visual Analogue Pain Scores <ul><li>Advantages </li></ul><ul><ul><li>Simple </li></ul></ul><ul><ul><li>Understandable </li></ul></ul><ul><ul><li>Rapidly recorded </li></ul></ul><ul><ul><li>Conventional </li></ul></ul><ul><li>Limitations </li></ul><ul><ul><li>Irrelevant </li></ul></ul><ul><ul><li>Variable </li></ul></ul><ul><ul><li>Subjective </li></ul></ul><ul><ul><li>Inaccurate </li></ul></ul>None Worst Assessment
  12. 12. VAS Scores And Laboratory Measures VAS Pain VAS Patient Global ESR <ul><li>Patient measures on VAS differ from joint counts </li></ul><ul><li>They also differ from ESR and C-reactive protein </li></ul><ul><li>“ Flatter” distribution </li></ul>
  13. 13. Correlations of Clinical Measures <ul><li>Tender Swollen Patient Pain </li></ul><ul><li>Joints Joints Global </li></ul><ul><li>ESR 0.14 0.25 0.24 0.21 </li></ul><ul><li>Pain 0.47 0.36 0.83 </li></ul><ul><li>Patient Global 0.48 0.34 </li></ul><ul><li>Swollen joints 0.51 </li></ul>
  14. 14. Combining Measures <ul><li>Indices </li></ul><ul><li>1977 Smyth - A pooled index </li></ul><ul><li>1981 Mallya - Index of disease activity </li></ul><ul><li>1990 Davis - Stoke index </li></ul><ul><li>1990 Van der Heijde - Disease Activity Score </li></ul><ul><li>1995 Symmons - Overall Status (OSRA) </li></ul><ul><li>1995 Prevoo - Modified DAS (28-joint counts ) </li></ul><ul><li>Response Criteria </li></ul><ul><li>American College of Rheumatology </li></ul><ul><li>Combine joint counts, patient/physician global assessments, pain, ESR and HAQ. </li></ul><ul><li>20%, 50% or 70% responses </li></ul>
  15. 15. Changes in DAS with TNF From Professor Piet Van Riel
  16. 16. Listening to Patients Self-Assessment can replace clinician assessment <ul><li>Patient-based disease activity score (PDAS) </li></ul><ul><ul><li>Accurate </li></ul></ul><ul><ul><li>Reproducible </li></ul></ul><ul><ul><li>Valid </li></ul></ul><ul><li>Equivalent to clinician assessments (DAS) </li></ul>
  17. 17. What is functional outcome? Disability and Health Status <ul><li>Focus on subjective assessments </li></ul><ul><ul><li>Questionnaires rather than direct measures </li></ul></ul><ul><li>HAQ dominates </li></ul><ul><ul><li>Good for groups, poor for individuals </li></ul></ul><ul><ul><li>Rarely used in routine practice </li></ul></ul><ul><li>Many alternative health status measures </li></ul><ul><ul><li>SF-36, Nottingham Health Profile, EuroQol </li></ul></ul><ul><ul><li>Some agreement, but important differences </li></ul></ul><ul><ul><li>Not interchangeable </li></ul></ul>
  18. 18. Measuring Disability Measuring Instruments <ul><li>Disease specific </li></ul><ul><ul><li>Health Assessment Questionnaire (HAQ) </li></ul></ul><ul><ul><li>Arthritis Impact Measurement Scale (AIMS) </li></ul></ul><ul><li>Generic </li></ul><ul><ul><li>Medical Outcome Study SF-36 </li></ul></ul><ul><ul><li>Nottingham Health Profile (NHP) </li></ul></ul>
  19. 19. Health Assessment Questionnaire Fries Contribution to Rheumatology
  20. 20. Components of HAQ Scores Results in 103 RA patients
  21. 21. Progression of HAQ Scores Four Key Studies in Early RA Five Key Studies in Established RA
  22. 22. Annual Change in the HAQ 25 cases followed for 5 years in London 105 cases followed for 12 years in Holland 3 2 1 0 3 6 9 12 Disease Duration in Years HAQ Score
  23. 23. Annual Increase of HAQ in Routine Practice Graphical Report of 13 studies
  24. 24. Limitations of Conventional Assessments Physician-measurement gives high placebo response <ul><li>1817 patients in trials </li></ul><ul><li>Physician-measurement (swollen joints) </li></ul><ul><ul><li>high effect sizes with placebo </li></ul></ul><ul><li>Patient-measurement (HAQ) </li></ul><ul><ul><li>Low effect sizes with placebo </li></ul></ul>Scott and Strand, Rheumatology, 2002
  25. 25. Comparing HAQ with EuroQol Different distributions shown in 320 RA patients
  26. 26. Health Profiles in RA Nottingham Health Profile Nottingham Health Profile
  27. 27. Health Profiles in RA Nottingham Health Profile Nottingham Health Profile
  28. 28. HAQ scores over the course of RA Changing correlations with time Welsing et al, Arthritis Rheum, 2000 <ul><li>HAQ-DAS   </li></ul><ul><li>    Baseline 0.40 </li></ul><ul><li>    6 years 0.79 </li></ul><ul><li>    9 years -0.02 </li></ul><ul><li>HAQ-Sharp Score   </li></ul><ul><li>    Baseline 0.15 </li></ul><ul><li>    6 years 0.75 </li></ul><ul><li>    9 years 0.57 </li></ul>Increases Over 10 Years Changing Correlations HAQ Score Months
  29. 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. 30. HAQ And DMARDs 6 month individual changes in HAQ from leflunomide trial (MN 301)
  31. 31. HAQ and DMARDs All phase III leflunomide trials (ITT analysis)
  32. 32. HAQ and DMARDs Sustained changes in HAQ during 2 years leflunomide HAQ Scores MN 305 (60 cases) MN 304 (248 cases) US 301 (97 cases)
  33. 33. Steroid/DMARD combinations in Early RA ARC (Kirwan) and Cobra studies ARC Cobra
  34. 34. Steroid/DMARD combinations in Late RA Adding IM Depomedrone to DMARDs Choy et al, Ann Rheum Dis, 2005 <ul><li>91 RA patients on DMARDs </li></ul><ul><ul><li>Partial responders </li></ul></ul><ul><li>Randomised to receive </li></ul><ul><ul><li>IM Depomedrone </li></ul></ul><ul><ul><li>Placebo </li></ul></ul><ul><li>Followed for 24 months </li></ul><ul><li>HAQ scores </li></ul><ul><ul><li>Minor short term improvements with steroids </li></ul></ul>
  35. 35. DMARD Combinations Adding leflunomide to Methotrexate Kremer et al, J Rheum, 2004 <ul><li>RA patients active despite adequate MTX therapy </li></ul><ul><li>263 randomised patients </li></ul><ul><ul><li>6 month RCT </li></ul></ul><ul><ul><li>6 month extension </li></ul></ul><ul><li>First 6 months </li></ul><ul><ul><li>Methotrexate/leflunomide </li></ul></ul><ul><ul><li>Methotrexate/Placebo </li></ul></ul><ul><li>Second 6 months </li></ul><ul><ul><li>Methotrexate/leflunomide </li></ul></ul>
  36. 36. DMARD combinations in Early RA FinRA-Co and MTX/SZP ( Maillefert) studies FinRA-Co MTX/SZP
  37. 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. 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. 39. Comparative Changes in HAQ Leflunomide versus Anti-TNF
  40. 40. Percent Changes In HAQ RCTs for registration of new DMARDs/biologics After Vibeke Strand
  41. 41. Measuring Quality of Life Improves Assessments of Anti-TNF <ul><li>20 RA patients </li></ul><ul><li>Treated with infliximab </li></ul><ul><li>Assessed at 3 months </li></ul><ul><li>RA QoL shows improvements </li></ul>Treatment Baseline RAQol Score 30 20 10 0
  42. 42. Aggressive DMARD regimens Aggressive/Standard DMARDs Late RA BROSG Study Early DMARDs/pyramidal NSAIDs Early RA Utrecht Arthritis Cohort Study HAQ
  43. 43. Intensive versus routine treatment TICORA trial in early RA Grigor et al, Lancet, 2004 <ul><li>Single-blind RCT </li></ul><ul><ul><li>111 RA patients </li></ul></ul><ul><ul><li>in Glasgow </li></ul></ul><ul><li>Randomised to receive: </li></ul><ul><ul><li>intensive management </li></ul></ul><ul><ul><li>routine care </li></ul></ul><ul><li>ITT analysis </li></ul><ul><ul><li>HAQ secondary outcome </li></ul></ul>
  44. 44. Explaining Relationships of HAQ Joint damage act as “regulator” Sets disability level in which day-to-day variation occurs Synovitis Joint damage Disability
  45. 45. Measuring Damage From normality to failed joints
  46. 46. Some X-ray Scoring Systems <ul><li>Year Authors Main features </li></ul><ul><li>1949 Steinbrocker 0-4 grading using standardised ARA criteria </li></ul><ul><li>1961 ERC gold study Separate erosion/joint space narrowing scores </li></ul><ul><li>1963 Kellgren Standard reference films </li></ul><ul><li>1969 Berens & Lin Global scale from 0 to 5 </li></ul><ul><li>1971 Sharp Erosion/oint space narrowing scores for hands </li></ul><ul><li>1976 Trentham & Masi Carpo-metacarpal ratio </li></ul><ul><li>1977 Amos Counting new erosions in hands and wrists </li></ul><ul><li>1977 Larsen Global score with standard reference films </li></ul><ul><li>1983 Genant Erosion/joint space narrowing scores with standard X-rays </li></ul><ul><li>1983 Bluhm Erosion/joint space narrowing scores with standard X-rays </li></ul><ul><li>1985 Scott Erosion/joint space narrowing/malalignment/total scores </li></ul><ul><li>1987 Kaye Erosion/joint space narrowing/malalignment/total scores </li></ul><ul><li>1989 Van der Heijde Modified Sharp index including feet </li></ul>
  47. 47. Changes in Larsen Score in Early RA Average of two observers <ul><li>Correlations </li></ul><ul><li>Initial Final Change </li></ul><ul><li>Pearson 0.87 0.93 0.70 </li></ul><ul><li>Spearman 0.86 0.80 0.60 </li></ul>
  48. 48. X-ray Progression Studies using Sharp and Larsen Scores Single Centre Cross-Sectional Study Longitudinal Studies From 8 centres
  49. 49. Correlating Damage With Disability 5 studies in early RA and 8 in late RA <ul><li>Study Year Cases Dur’n Correl Signif </li></ul><ul><li>Eberhardt 1995 63 Early 0.27 NS </li></ul><ul><li>van Leeuwen 1994 149 Early 0.31 P<0.001 </li></ul><ul><li>Plant 1997 89 Early 0.32 p<0.01 </li></ul><ul><li>Uhlig 2000 238 Early 0.64 p<0.001 </li></ul><ul><li>Welsing 2001 131 Early 0.06 NS </li></ul><ul><li>Kaarela 1993 103 Late 0.68 p<0.001 </li></ul><ul><li>Larsen 1988 200 Late NA P<0.01 </li></ul><ul><li>Regan Smith 1989 54 Late NS NS </li></ul><ul><li>Pincus 1989 259 Late 0.31 p<0.001 </li></ul><ul><li>Hakala 1994 103 Late 0.46 P<0.001 </li></ul><ul><li>Houssein 1997 126 Late 0.38 p<0.001 </li></ul><ul><li>Drossaers-Bakker 2000 105 Late 0.60 p<0.001 </li></ul><ul><li>Welsing 2001 39 Late 0.57 p<0.001 </li></ul>
  50. 50. Large Joint Damage And Disability Effect on HAQ score after 12 years RA <ul><li>Impact on Disability </li></ul><ul><li>Multivariate analysis </li></ul><ul><li>Disease Activity 36% </li></ul><ul><li>Large Joint Damage 16% </li></ul><ul><li>Psychological status 5% </li></ul><ul><li>Small joint damage 3% </li></ul>Drossaers-Bakker et al, Rheumatology, 2000
  51. 51. Digression on Steroids: Historical Perspective Major Breakthrough in RA Over 50 Years Ago Philip Hench Edward Kendall Tadeus Reichstein “ it is still too early to judge what role cortisone may play as a remedy for cases of rheumatoid arthritis” Nobel Prize: Medicine, 1950 Presentation Speech by Prof Liljestrand ACTH Case From First Clinical Paper On Steroids in RA 45 year old female with severe RA for 5 years
  52. 52. New Role in 1990’s Combined with DMARDs In Early RA to Prevent Erosions Approaches Constant Low Dose Tapering High Dose Kirwan, NEJM, 1995 van Everdingen Ann Intern Med 2002 Boers, Lancet, 1997
  53. 53. IM Depomedrone In Established RA RCT Comparing 2-Years Monthly Depomedrone with Placebo in patients on DMARDs
  54. 54. The Popert Regimen A Strong Belief in Combination Therapy <ul><li>Beliefs </li></ul><ul><li>Prolonged inpatient care needed </li></ul><ul><li>Seek remission at all costs </li></ul><ul><li>Approach </li></ul><ul><li>Admit >6/52 each year </li></ul><ul><li>Start chloroquine </li></ul><ul><li>If insufficient </li></ul><ul><ul><li>add gold </li></ul></ul><ul><ul><li>add>20mg steroids </li></ul></ul><ul><ul><li>add other DMARDs </li></ul></ul>Highfield Hospital Patients’ Lounge
  55. 55. 20 Year Results At Droitwich
  56. 56. RA Mortality An Overview <ul><li>RA reduces the length of life </li></ul><ul><li>14 main studies since 1980 </li></ul><ul><ul><li>13,424 patients </li></ul></ul><ul><ul><li>Mean SMR 1.8 (Range 0.87-3) </li></ul></ul><ul><ul><li>Life expectancy shortened by 5-10 years </li></ul></ul><ul><li>Factors predictive of premature death same as those predicting disability </li></ul>Guedes et al, Rev Rhum, 1999
  57. 57. Cause-Specific Mortality RA Deaths In 20 Year Follow-up Study 9003 Scottish RA inpatients 1981-2000 Thomas et al, J Rheumatol, 2003
  58. 58. Cause-Specific Mortality RA SMR in 20 Year Follow-up Study 9003 Scottish RA inpatients 1981-2000 Thomas et al, J Rheumatol, 2003
  59. 59. Cardiovascular Mortality in Women RA 114 342 nurses without heart disease and RA in 1976 After 20 years: 527 had RA, 2296 had MIs and 1326 strokes Solomon et al, Circulation, 2003
  60. 60. Mortality and Vascular Deaths RA, OA and No Arthritis From UK GP Database Women Men Watson et al, J Rheumatol, 2003
  61. 61. Deaths From Ischaemic Heart Disease SMR in 4 Studies of RA Patients
  62. 62. Deaths in Early Polyarthritis 1236 patients in NOAR Goodson et al, Arthritis Rheum, 2002
  63. 63. Cardiovascular Events In RA Unexplained by usual risk factors in 236 cases <ul><li>Predictor Rel Risk 95% CI </li></ul><ul><li>RA 3.17 1.33-6.36 </li></ul><ul><li>Diabetes 2.28 1.65-3.12 </li></ul><ul><li>Age 2.15 1.83-2.55 </li></ul><ul><li>Sex 1.99 1.50-2.66 </li></ul><ul><li>Cigarettes 1.37 1.01-1.83 </li></ul><ul><li>Cholesterol 1.35 1.01-1.82 </li></ul><ul><li>Blood pressure 1.18 1.03-1.33 </li></ul><ul><li>Body mass index 1.13 0.99-1.28 </li></ul>Del Rincón et al, Arthritis Rheum 2001
  64. 64. Cardiovascular Risk Factors Comparison of OA and RA Dessein et al, Arthritis Research, 2002
  65. 65. Alternative Assessment of Risk Factors in RA
  66. 66. Joint Swelling And Cardiovascular Deaths Prospective Study of 4120 Pima Indians Jacobsson et al, Arthritis Rheum, 2001 Joint swelling predicts CVD-related death Independent of other risks including diagnosis of RA Men Women
  67. 67. Predicting Mortality in RA 20 year study of 1381 Cases ESR Rheumatoid Factor Woolf et al, Arthritis Rheum, 2003 HAQ is another strong predictor
  68. 68. Mortality With DMARDs Risks compared to no DMARDs 1240 RA patients and 191 deaths Choi et al, Lancet, 2002
  69. 69. Deaths With Methotrexate Reduced CVS Mortality Choi et al, Lancet, 2002
  70. 70. Deprivation Predicts Death in RA Long Term Results from Glasgow
  71. 71. The patient's journey with RA Carol Simpson and Chloe Franks (patients) BMJ, October 2005
  72. 72. The patient's journey with RA Carol Simpson and Chloe Franks (patients) BMJ, October 2005 <ul><li>Bad News </li></ul>Good News
  73. 73. The patient's journey with RA Carol Simpson and Chloe Franks (patients) BMJ, October 2005 <ul><li>Bad News </li></ul><ul><li>Unsuccessful drug treatments are a major concern and reality for many patients </li></ul><ul><li>High level of uncertainty for each new drug used </li></ul>Good News Emergence of the new biological drugs has given new hope to people living with RA
  74. 74. Patient’s stories: Chloe <ul><li>“ I have tried a variety of treatments, including all the anti-TNF medications. Unfortunately I have been extremely unlucky because they have not been effective or I have had an allergic reaction to them” </li></ul><ul><li>“ I have had very little or no remittance, which is very wearing both physically and emotionally” </li></ul>
  75. 75. Patients Stories: Carol <ul><li>“ My drug treatment for RA has not been at all successful... frequently the effect of the medication has worn off after 2-3 weeks.” </li></ul><ul><li>“ My anger has not been towards the doctors but with myself. In my opinion the reactions to the medication are much worse than the disease itself.” </li></ul>
  76. 76. Strengths and Weaknesses in Clinics Qualitative Research at Kings <ul><li>Good Features </li></ul><ul><li>Explained treatments </li></ul><ul><li>Showed tests </li></ul><ul><li>Offered choices </li></ul>
  77. 77. <ul><li>Good Features </li></ul><ul><li>Explained treatments </li></ul><ul><li>Showed tests </li></ul><ul><li>Offered choices </li></ul><ul><li>Problems </li></ul><ul><li>Conflicting messages </li></ul><ul><li>No explanations </li></ul><ul><li>Not listened to </li></ul>Strengths and Weaknesses in Clinics Qualitative Research at Kings
  78. 78. UK Standards of Care Arthritis and Musculoskeletal Alliance <ul><li>People have rights to: </li></ul><ul><li>Access to appropriate services </li></ul><ul><li>Timely diagnosis and treatment </li></ul><ul><li>Information </li></ul><ul><li>Services centred on users’ needs </li></ul><ul><li>Independence </li></ul><ul><li>Self-determination </li></ul>
  79. 79. UK Standards of Care Arthritis and Musculoskeletal Alliance <ul><li>Information and knowledge </li></ul><ul><li>Early diagnosis and treatment </li></ul><ul><li>Ongoing treatment and support </li></ul>
  80. 80. Key Components of ARMA Standards <ul><li>Information and knowledge </li></ul><ul><ul><li>Self-management guidance </li></ul></ul><ul><ul><li>When to seek advice </li></ul></ul><ul><li>Early diagnosis and treatment </li></ul><ul><ul><li>Early access to expert advice </li></ul></ul><ul><ul><li>Patient involvement in service development </li></ul></ul><ul><li>Ongoing treatment and support </li></ul><ul><ul><li>Multi-disciplinary teams </li></ul></ul><ul><ul><li>Regular specialist reviews </li></ul></ul>
  81. 81. Supporting People with Long Term Conditions <ul><li>Linked NHS Programmes </li></ul><ul><li>Disease management </li></ul><ul><ul><li>Improving pathways and protocols </li></ul></ul><ul><li>Case management </li></ul><ul><ul><li>Patients with complex long term conditions </li></ul></ul><ul><li>Self Care </li></ul><ul><ul><li>Expert patients </li></ul></ul>
  82. 82. Key Issue in UK Need for Early Treatment <ul><li>Early access to specialist advice </li></ul><ul><ul><li>Currently 3 months </li></ul></ul><ul><ul><li>Want under 6 weeks </li></ul></ul><ul><li>Rationale </li></ul><ul><ul><li>Early diagnosis </li></ul></ul><ul><ul><li>Effective treatment </li></ul></ul>
  83. 83. Key Points <ul><li>RA causes damage and disability </li></ul><ul><ul><li>both increase by about 1%/year </li></ul></ul><ul><li>Mortality is increased in RA </li></ul><ul><ul><li>Average SMR 1.8, but not all studies show increase </li></ul></ul><ul><ul><li>Mortality worse in severe seropositive RA </li></ul></ul><ul><li>Cardiovascular mortality also increased </li></ul><ul><ul><li>Linked to high CRP, diabetes and steroids </li></ul></ul><ul><ul><li>Unclear if increased risk is due to RA or ill-health? </li></ul></ul>

×