Radiographic scoring in rheumatoid arthritis - The basics
Tuulikki Sokka, MD, PhD [email protected] Slide 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 Slide 3 History; the main methods
Steinbrocker 1949 Kellgren 1956 Sharp 1971 Van der Heijde
modification Larsen 1973 modifications Slide 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 Slide 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 Slide 6 Sharp method (1) Purpose: to develop a quantitative
assessment for radiographic changes in RA Included:
Hands&wrists Slide 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 Slide 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 Slide 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 Slide 10 Sharp method (4)
Joint space narrowing score; principles 0 - normal 1 - focal
narrowing 2 reduction of 50% of joint space 4 ankylosis 27 areas in
hands and wrists max score 216 Slide 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. Slide 12 Van der Heijde
modification of the Sharp score PRINCIPLES Feet included Number of
hand joints decreased Scoring for erosions defined Slide 13 The
Sharp/van der Heijde: Joints to be scored for erosions Slide 14 The
Sharp/van der Heijde: Joints to be scored for joints space
narrowing Slide 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 Slide 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
Slide 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 4 ankylosis
Slide 18 Sharp van der Heijde method (4) Total scores: Erosion
scores for hands160 Erosion scores for feet120 JSN for hands120 JSN
for feet 48 Total448 Slide 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 Slide 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 Slide 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
Slide 22 Larsen 0-100 Slide 23 Larsen scoring Slide 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 Slide 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 Slide 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 Slide 27 Radiographic scores in
RCTs - interpretations Slide 28 Yazc Y, Yazc H, Arthritis Rheum
2006;54(supl) Radiographic progression in selected clinical trials
Slide 29 MTX (n = 206) Etan (n = 202) Etan + MTX (n = 212) Year 2
Total Sharp score (0-448) Mean (95% CI)3.34 (1.18, 5.50)1.10 (0.13,
2.07) -0.56 (-1.05,-0.06) Median (IQR)0.00 (-0.11, 2.33)0.00
(-0.66, 1.08) 0.00 (-1.41, 0.05) 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
vdHeijde A&R2006 Slide 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 Slide 31 Measures of RA
over time: short term vs. long term Short 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 CostsMortality =
measures of outcomes RCTs Clinical cohorts, longitudinal
observational studies, databases Slide 32 Radiographs clinical use
Slide 33 Two clusters of measures in RA x-rays HAQ joint deformity
disease duration pain RF+joint tenderness joint swelling ESR,
CRPage HLA-DR4patient global work disability mortality Pincus,
Sokka. Best Pract Res Clin Rheumatol. 2003 Slide 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 ) Slide 35 Larsen & Thoen Scand J Rheumatol
1987 Disease duration, years 0 2 4 6 8 10 12 14 16 18 20 22 24 100%
75% 50% 25% 0% Damage score 0-100 Slide 36 Fuchs et al. J Rheumatol
1989 Disease duration, years 0 2 4 6 8 10 12 14 16 18 20 22 24 100%
75% 50% 25% 0% Erosion score 0 - 4.33 Slide 37 Salaffi &
Ferraccioli Scand J Rheumatol 1989 0 2 4 6 8 10 12 14 16 18 20 22
24 Disease duration, years Erosion score 0 - 150 100% 75% 50% 25%
0% Slide 38 The Jyvskyl Experience The Central Finland RA register
includes all patients with diagnosis of RA since 1980s; prospective
in all patients since 1996 2,900 patients; 2,300 alive Covers a
population of 265,000 Slide 39 The North Pole Slide 40 Jyvskyl
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 Slide 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
Slide 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 Slide 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
Slide 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 2000-2005; 2007
Slide 45 Radiographic outcomes in selected clinical cohorts Slide
46 Patients with early RA: 1983-85 1983-85 1988-89 1988-89 1995-96
1995-96 Radiographic outcomes over 5 years in 3 Jyvaskyla Cohorts:
Slide 47 1983-85 1995-96 1988-89 Larsen scores of RF+ patients over
5 years Sokka et al. J Rheumatol 2004 Each line illustrates Larsen
score of each patient Slide 48 1983-85 DMARDs over 5 years:
Increasing use over time 1988-89 1995-96 Sokka et al. J Rheumatol
2004 Slide 49 Radiographic outcomes of RF+ patients over 5 Years in
3 cohorts of patients with early RA. 1983-851988-891995-96 N465338
Patients with an erosive disease at 5 years, % 86%67%73% Patients
with Larsen >=10,% Baseline9%03% 2 years40%20%8% 5
years55%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 Slide 50
Radiographic outcomes in two cohorts The Heinola Cohort: 103
patients with early RA in the 1970s The Heinola Cohort: 103
patients with early RA in the 1970s The Jyvaskyla Cohort: 85
patients with early RA in the 1980s The Jyvaskyla Cohort: 85
patients with early RA in the 1980s All RF+ All RF+ 8-year
follow-up 8-year follow-up Slide 51 Larsen score in the Heinola
Cohort vs. Jyvaskyla Cohort over 8 years Disease duration (years)
12% Sokka T, Kaarela K, Mottonen T, Hannonen P. Clin Exp Rheumatol
1999 26% Slide 52 Increased use of DMARDs in the later cohort
Heinola 1973-75 103 patients Early RA RF+ Jyvaskyla 1983-89 85
patients Early RA RF+ saw tooth strategy Sokka et al CER 1999 Slide
53 Pincus, Sokka, Kautiainen A&R 2005 Median values with 95%
confidence intervals for the Larsen score in patients with 15 years
of disease in 1985 and 2000 in TPclinic Slide 54 Contemporary
DMARDs in the 1985 Cohort Pincus, Sokka, Kautiainen A&R 2005
Slide 55 Contemporary DMARDs in the 2000 Cohort Pincus, Sokka,
Kautiainen A&R 2005 Slide 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 Slide 57 32 nd
Scandinavian Congress of Rheumatology 30 January - 3 February 2008
Levi, Lapland, Finland Further information: www.congrex.fi/scr2008
Slide 58 Slide 59 To read: van der Heijde D. How to read
radiographs according to the Sharp/van der Heijde method. J
Rheumatol 1999; 26:743-745. Kaarela K, Kautiainen H. Continuous
progression of radiological destruction in seropositive rheumatoid
arthritis. J Rheumatol 1997; 24:1285-1287.
