1. Radiographic scoring in rheumatoid arthritis - The basics
Tuulikki Sokka, MD, PhD

2. Learning Objectives History of different scoring methods
Basics of the most often used methods
Interpretation of radiographic scores in clinical trials
Clinical use of radiographs
Radiographic outcomes in selected clinical cohorts

3. History; the main methods
Steinbrocker 1949
Kellgren 1956
Sharp 1971
Van der Heijde modification
Larsen 1973
modifications

4. Steinbrocker method Stage I - IV Relates to “anatomic stages”
radiographs of hands&wrists
The grade is determined by the worst change in any joint
Limitations: narrow scale; bias toward the most severely affected joint

5. Kellgren method 0-4, based on standard set of radiographs
“global” – one grade is given as a summation of abnormalities for all the joints in both hands and wrists
Limitations: narrow scale; weighted to reflect the most damaged joints

6. Sharp method (1)
Purpose: to develop a quantitative assessment for radiographic changes in RA
Included: Hands&wrists

7. Sharp method (2) Initially, 10 features were analyzed:
Periosteal reaction
Cortical thinning
Osteoporosis
Sclerosis
Osteophyte formation
Defects
Cystic changes
Surface erosions
Joint space narrowing
Ankylosis
Reason to delete items:
Rare
Technical problems
Secondary changes

8. Sharp method (2) Initially, 10 features were analyzed:
Periosteal reaction
Cortical thinning
Osteoporosis
Sclerosis
Osteophyte formation
Defects
Cystic changes
Surface erosions
Joint space narrowing
Ankylosis
Rare
Technical problems
Secondary changes
INCLUDED:
Erosion score
Joint space narrowing

9. Sharp method (3) Erosion score; principles: Score 0-5 for each joint
one point for each erosion in each joint and 5 for total destruction
29 areas were analyzed in both hands+wrists – maximum possible score: 290

10. Sharp method (4) Joint space narrowing score; principles
0 - normal
1 - focal narrowing
2 – reduction of <50% of joint space
3 – reduction of >50% of joint space
4 – ankylosis
27 areas in hands and wrists – max score 216

11. Sharp method (5) How many joints? (1985) Factors to be considered:
Frequency of involvement
Technical factors
Minimum number of joints required in a patient population from mild to severe disease:
17 for erosions
18 for joint space narrowing
….. Still to decrease………………….

12. Van der Heijde modification of the Sharp score
PRINCIPLES
Feet included
Number of hand joints decreased
Scoring for erosions defined

13. The Sharp/van der Heijde:
Joints to be scored for erosions

14. The Sharp/van der Heijde:
Joints to be scored for joints space narrowing

15. Sharp van der Heijde method (1) Erosions
Scoring of the hands: 16 areas included
Score 0-5 per joint
1 – for discrete erosions
2-3 for larger erosions depending of the surface area involved
4 if erosion extends over middle of the bone
5 for complete collapse

16. Sharp van der Heijde method (2) Erosions
Scoring of the feet: 10 MTP and 2 IP joints of big toes
Score 0-5 per each side of the joint: total 0-10
1 – for discrete erosions
2-3 for larger erosions depending of the surface area involved
4 if erosion extends over middle of the bone
5 for complete collapse

17. Sharp van der Heijde method (3) JSN, hands, feet
Joint space narrowing score; 15 areas for hands, 6 for feet
0 - normal
1 - focal narrowing
2 – reduction of <50% of joint space
3 – reduction of >50% of joint space
4 – ankylosis

18. Sharp van der Heijde method (4)
Total scores:
Erosion scores for hands 160
Erosion scores for feet 120
JSN for hands
JSN for feet
Total

19. Larsen score (1) Background was a clinical observation:
“A man with RA Steinbrocker 4 running to a bus”
Steinbrocker 4 is maximal damage
Max damage and running to a bus do not match
A better scoring method needed

20. Larsen score (2) Reference films for each joint
Score 0-5 for each joint
Scoring includes JSN and erosions
Articular osteoporosis and soft tissue swelling were initially included but omitted later

21. Larsen score (3) Which joints?
Scott 1995: 10 PIPs, 10 MCPs, 10 MTPs, wrists multiplied by 5 – total score 200
Kaarela & Kautiainen 1997: 10 MCPs, II-V MTPs, wrists not multiplied – total score 100

22. Larsen 0-100

23. Larsen scoring

24. Larsen vs. Sharp Are significantly correlated
Pincus et al. J Rheumatol 1997
Larsen less time-consuming and easier
overall scoring for each joint
wrist analyzed as one joint
lower number of joints

25. Smallest Detectable Difference SDD
SDD is the smallest change that can be reliably discriminated from the measurement error of the scoring method
SDD is based on defining measurement error and 95% limits of agreement
Sharp vd Heijde on scale 448; SDD = 5
Larsen on scale 200; SDD = 5.8
Bruynesteyn et al. A&R 2002

26. Minimal Clinically Important Difference MCID
MCID = progression with the highest combined sensitivity and specificity for detecting relevant progression
Sharp vd Heijde on scale 448; MCID = 4.6
Larsen on scale 200; MCID = 2.3
In both, roughly 1% of the maximum
Bruynesteyn et al. A&R 2002

27. Radiographic scores in RCTs - interpretations

28. Radiographic progression in selected clinical trials
Yazıcı Y, Yazıcı H, Arthritis Rheum 2006;54(supl)

29. Low radiographic damage in current RCTs:
Table 3. Change from baseline in disease characteristics in the ITT population after 2 years of treatment in the TEMPO trial
MTX (n = 206) Etan (n = 202) Etan + MTX (n = 212)
Year 2   
Total Sharp score (0-448)   
   
Mean (95% CI) (1.18, 5.50) 1.10 (0.13, 2.07) (-1.05,-0.06)     
Median (IQR) (-0.11, 2.33) 0.00 (-0.66, 1.08) (-1.41, 0.05)
vdHeijde A&R2006

30. Few patients have radiographic damage in current RCTs: Total Sharp vdHeijde score (0-448) in the TEMPO trial over 2 years
vdHeijde A&R2006

31. Measures of RA over time: short term vs. long term
Months - years
Swollen joint count
Tender joint count
ESR, CRP
Pain
Functional capacity
Global health by patient
Global health by Dr
(Radiographic damage; >1yr)
= measures of disease activity
Long term
Years - decades
Deformities
Radiographic damage
Joint replacements
Functional capacity
Comorbidity
Work disability
Costs
Mortality
= measures of outcomes
Clinical cohorts, longitudinal observational studies, databases
RCTs

32. Radiographs – clinical use

33. Two clusters of measures in RA
x-rays HAQ
joint deformity
disease duration pain
RF+ joint tenderness
joint swelling
ESR, CRP age
HLA-DR4 patient global
work disability
mortality
Pincus, Sokka. Best Pract Res Clin Rheumatol. 2003

34. The HAQ, CLINHAQ, or MDHAQ Patient Questionnaire – is Best Predictor in RA of…
Functional status (Pincus et al. Arthritis Rheum. 1984, Wolfe et al. J Rheumatol. 1991)
Work disability (Borg et al. J Rheumatol 1991, Callahan et al. J Clin Epidemiol. 1992, Wolfe and Hawley. J Rheumatol. 1998, Fex et al. J Rheumatol 1998, Sokka et al. J Rheumatol 1999, Barrett et al. Rheumatology 2000, )
Costs (Lubeck et al. Arthritis Rheum. 1986)
Joint replacement surgery (Wolfe and Zwillich. Arthritis Rheum. 1998)
Death (Pincus et al. Arthritis Rheum. 1984, Ann Intern Med.1994, Wolfe et al. J Rheumatol 1988, Leigh&Fries J Rheumatol 1991, Wolfe et al. Arthritis Rheum. 1994, Callahan et al. Arthrits Care Res 1996, 1997, Soderlin et al. J Rheumatol 1998, Maiden et al. Ann Rheum Dis 1999, Sokka et al. Ann Rheum Dis 2004)

35. Larsen & Thoen Scand J Rheumatol 1987
100%
75%
50%
25% 0%
Damage score 0-100
Disease duration, years

36. Fuchs et al. J Rheumatol 1989 100% Erosion score 0 - 4.33 75% 50% 25%
Disease duration, years

37. Salaffi & Ferraccioli Scand J Rheumatol 1989
100%
75%
50%
25% 0%
Erosion score
Disease duration, years

38. The Jyväskylä Experience
The Central Finland RA register includes all patients with diagnosis of RA since 1980’s; prospective in all patients since 1996
2,900 patients; 2,300 alive
Covers a population of 265,000

39. The North Pole

40. Jyväskylä Central Hospital is the only rheumatology clinic in the Central Finland District and serves a population of 265,000
2 full-time rheumatologists and 1 trainee
+ 4 other rheumatologists

41. The Central Finland RA Register
Patient demographics
History of onset of RA
Classification criteria
Extra-articular features
Comorbidities
Relevant surgeries
All previous and present DMARDs

42. Patients with early arthritis
All new patients with RA are included; about 100 early RA patients each year
Baseline data includes patient self-report questionnaires, structured clinical status, laboratory tests, radiographs of hands and feet

43. Patient Monitoring in early RA since 1997
Regular out-patient visits in rheumatology unit for 2 years
A control visit at 1, 2, 5, and 10 years including patient self-reported outcomes, structured clinical status, update of RA register information, laboratory tests including RF and aCCP, and radiographs of hands and feet

44. Patient Monitoring
Each visit, every patient is asked to complete an extended 2-page HAQ or self-report on a touch screen / GoTreatIT
Rheumatologist: a status form / GoTreatIT
An annual mailed questionnaire to all patients in the RA Register since 1998
A 5-year follow-up of 2000 population controls in ; 2007

45. Radiographic outcomes in selected clinical cohorts

46. Radiographic outcomes over 5 years in 3 Jyvaskyla Cohorts:
Patients with early RA:

47. of RF+ patients over 5 years 1995-96
Larsen scores
of RF+ patients over 5 years
Each line illustrates Larsen score of each patient
Sokka et al.
J Rheumatol 2004

48. Increasing use over time 1988-89
DMARDs over 5 years:
Increasing use over time
Sokka et al.
J Rheumatol 2004

49. Radiographic outcomes of RF+ patients over 5
Years in 3 cohorts of patients with early RA. N
Patients with an erosive disease at 5 years, %
86% 67% 73%
Patients with Larsen >=10,%
Baseline 9% 0 3%
2 years 40% 20% 8%
5 years 55% 33% 14%
Patients in the most recent cohort have potential for an erosive disease but the extent of damage remained low compared to earlier cohorts.
Sokka et al. JRheumatol 2004

50. Radiographic outcomes in two cohorts
The Heinola Cohort: 103 patients with early RA in the 1970’s
The Jyvaskyla Cohort: 85 patients with early RA in the 1980’s
All RF+
8-year follow-up

51. Larsen score in the Heinola Cohort vs. Jyvaskyla Cohort over 8 years
26%
12%
Disease duration (years)
Sokka T, Kaarela K, Mottonen T, Hannonen P. Clin Exp Rheumatol 1999

52. DMARDs in the later cohort
Increased use of
DMARDs in the later cohort
Heinola
103 patients
Early RA
RF+
Jyvaskyla
85 patients
Early RA
RF+
“saw tooth strategy”
Sokka et al CER 1999

53. Median values with 95% confidence intervals for the Larsen score in patients with <5, 5-15 and > 15 years of disease in 1985 and 2000 in TPclinic T o t a l - 4 5 1 D i s e d u r n ( y ) 2 3 L c p
< .
Pincus, Sokka, Kautiainen A&R 2005

54. Contemporary DMARDs in the 1985 Cohort
Pincus, Sokka, Kautiainen A&R 2005

55. Contemporary DMARDs in the 2000 Cohort
Pincus, Sokka, Kautiainen A&R 2005

56. Scoring of x-rays in RCTs vs. in clinical care
Experienced assessors read x-rays
Observers blinded to clinical data
Observers blinded to the order of radiographs
Strict methodology to get accurate scores
Every clinician to have basic knowledge about x-rays
X-rays add to clinical data
Serial x-rays to be compared to detect progression/improvement
Understanding of radiographic progression

57. 32nd Scandinavian Congress of Rheumatology
30 January - 3 February 2008
Levi, Lapland, Finland
Further information:

59. To read:
van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 1999; 26:
Kaarela K, Kautiainen H. Continuous progression of radiological destruction in seropositive rheumatoid arthritis. J Rheumatol 1997; 24: