Transcript Slide 1

A proposed 15 second
checklist of 10 measures
for all usual care
rheumatology visits
Theodore Pincus, MD
Clinical Professor of Medicine
New York University school of Medicine
[email protected]
1
0%
0%
5
0%
3
0%
2
0%
1
1. Presence of
rheumatoid factor
2. Poor functional status
3. Quantitative
radiographic score
4. Presence of ACRA
(anti-CCP)
5. Number of swollen
joints
4
What is the most significant risk factor
for mortality over 5-20 years in patients
with RA?
5
2
What is the number of units in a
Sharp/van der Heidje radiographic
score?
5
0%
44
8
0%
22
4
0%
12
8
64
0%
0%
66
0
1. 64
2. 128
3. 224
4. 448
5. 660
3
Approximately what proportion of new
patients with RA have an ESR greater than
28mm/Hr?
1. 50%
2. 60%
3. 70%
4. 80%
5. 90%
5
0%
90
%
0%
80
%
0%
70
%
0%
60
%
50
%
0%
4
Approximately what proportion of new patients with
rheumatoid arthritis have anti-citrullinated peptide
antibodies (ACPA or anti-CCP)?
1. 50%
2. 60%
3. 70%
4. 80%
5. 90%
5
0%
90
%
0%
80
%
0%
70
%
0%
60
%
50
%
0%
5
What is the primary reason that “revolutionary”
new biological therapies for RA lead to only
60% ACR 20 responses?
5
n.
..
...
of
n
De
sig
o
et
Da
m
ag
c li
jo
in
gia
ya
l
Fib
ro
m
d
rg
et
e
No
nta
1. Non-targeted
different cytokines
causing
inflammation
2. Fibromyalgia
3. Damage to joints
4. Design of clinical
trails
d.
..
25% 25% 25% 25%
A proposed 15 second
checklist of 10 measures
for all usual care
rheumatology visits
Theodore Pincus, MD
Clinical Professor of Medicine
New York University school of Medicine
[email protected]
7
A checklist is a type of
informational job aid used to
reduce failure by
compensating for potential
limits of human memory and
attention. It helps to ensure
consistency and
completeness in carrying
out a task. A basic example
is the "to do list.”
• An airline pilot (and now
often a surgeon) must
complete a standard
checklist before using
his/her skills to fly an
airplane (or operate).
Surgical Safety Checklist
•Has the patient confirmed his/her identity,
site, procedure, and consent?
•Is the site marked?
•Is the anaesthesia machine and medication
check complete?
•Is the pulse oximeter on the patient and
functioning?
•Does the patient have a known allergy?
•Difficult airway or aspiration risk?
•Risk of >500ml blood loss (7ml/kg in
children)?
•How many agree with these statements?
•Rheumatologists help their patients as
much as any specialist helps any group
of patients
•Rheumatology care is
underappreciated by the general
medical community, public, payers
•A primary explanation may be that
rheumatologists generally little data to
document improvement quantitatively
• Why shouldn’t a
rheumatologist follow a
“scientific” procedure
similar to pilots and
surgeons to use a
quantitative checklist at
each patient visit before
using skills in clinical care?
Question for Rheumatologists
For patients with RA under your care (not including
patients in clinical trials), how often do you perform
formal tender and swollen joint counts?
Never
13%
32%
1%–24% of visits
25%–49% of visits
50%–74% of visits
75%–99% of visits
Always
11%
14%
16%
14%
Pincus T, et al. Ann Rheum Dis. 2006;65:820-822.
Clinical Decisions Survey
All clinical encounters for diagnosis and
management of different diseases include
5 sources of clinical information:
Clinician-intensive
(1) patient history
(2) physical examination
Clinician-non-intensive
(3) vital signs
(4) laboratory tests
(5) ancillary data, e.g., imaging
studies, endoscopies, etc.
Clinical Decisions Survey
• Please indicate your opinion of the
importance of each of 5 sources to provide 020%, 21-40%, 41-60%, 61-80%, or 81-100% of
information for diagnosis and management
of 8 diseases:
1. hypertension
2. diabetes mellitus
3. rheumatoid arthritis
4. hypercholesterolemia
5. pulmonary fibrosis
6. ulcerative colitis
7. lymphoma
8. congestive heart failure
Highest ranked source of clinical information 588
>50%:
20-50%:
<20%:
MDs:
Element
Cong
Heart
Failure
Diabetes
Melllitus
Hypertension
Hyperlipidemia
Lymphoma
Pulmonary
Fib
Vital
Signs
Patient
History
Physical
Exam
Lab
tests
Other
studies
McCollum, Durusu Tanriover, Akalžn ,
H Yazici, Pincus: EULAR 2010
Rheumat
Arthritis
UlcerativeC
oli-tis
•Most rheumatologists say that a patient
history and doctor’s physical examination
are more important than laboratory tests in
clinical decisions.
•However, the only quantitative data in the
usual medical record are laboratory tests.
•Therefore, only “gestalt” narrative
“unscientific” MD opinions are available to
try to recognize whether patients are better
or worse over long periods.
•Despite clinical advances, most
rheumatology patient encounters are
conducted very similarly to 40 years ago.
Standard scientific measures in
medical care
Disease
Hypertension
Diabetes
Standard Biomarker Biomarker
Biomarker Measure Measure in
Measure in clinical
clinical
trials
care
Blood
Blood
pressure pressure
Glucose, Glucose,
Hgb A1c
Hgb A1c
RheumaRF,
ACR Core
toid
anti-CCP, Data Set,
Arthritis ESR, CRP
DAS28
Blood
pressure
Glucose,
Hgb A1c
Standard scientific measures in
medical care
Disease
Standard Biomarker Biomarker
Biomarker Measure Measure in
Measure in clinical
clinical
trials
care
Hypertension
Diabetes
Blood
pressure
Glucose,
Hgb A1c
RF,
anti-CCP,
ESR, CRP
Blood
Blood
pressure pressure
Glucose, Glucose,
Hgb A1c
Hgb A1c
RheumaRF,
ACR Core
toid
anti-CCP, Data Set,
Arthritis ESR, CRP
DAS28
Why is a checklist needed for
optimal assessment of patients
with rheumatic diseases?
• No single ‘Gold Standard’ measure, e.g.,
blood pressure, cholesterol, glucose, for
diagnosis and management in all individual
patients
• Laboratory tests, the primary source of
quantitative data in many diseases, are
limited in rheumatic diseases
• Indices of 3–7 measures, based on Core
Data Set used in formal clinical research
RA Core Data Set – 7 or 8 measures
Source:
MD
exam
Tender joint count
√√
Swollen joint count
√√
Assessor Global estimate
√√
X- Lab
Patient
ray
self-report
√√
ESR or CRP
Phys Function-HAQ,MDHAQ
√√
Pain
√√
Patient Global estimate
√√
Radiographic score if >1 yr
√√
Felson et al, Arthritis Rheum 36:729, 1993.
van Riel, Br J Rheumatol 31:793, 1994.
What should be included in a
rheumatology visit checklist?
Types of measures in care of
patients with rheumatic diseases:
•Laboratory tests
•Joint counts
•Radiographic scores
•Patient questionnaire scores
Laboratory tests
for a rheumatology
visit checklist?
Textbook statements concerning
ESR in RA
"the erythrocyte sedimentation rate is increased
in nearly all patients with active RA”
Lipsky PE. Rheumatoid arthritis. In: Fauci AS, Langford CA,
eds. Harrison's Medicine. New York: McGraw-Hill,2006:85.
“at least 5% of patients with clinically active
disease may have a normal ESR”
Chatham WW, Blackburn WD, Jr. Laboratory findings in
rheumatoid arthritis. In: Koopman WJ, Moreland LW,
editors. Arthritis and allied conditions: a textbook of
rheumatology. Philadelphia, PA: Lippincott, Williams &
Wilkins, 2005:1207
Traditional approaches to clinical expertise:
EMINENCE BASED MEDICINE - making the
same mistakes with increasing confidence over an
impressive number of years
ELOQUENCE BASED MEDICINE - a year-round
suntan and brilliant oratory may overcome absence
of any supporting data
ELEGANCE BASED MEDICINE - where the
sartorial
splendor of a silk-suited sycophant substitutes for
substance
The modern alternative?
EVIDENCE BASED MEDICINE - the best
approach
to clinical data - requires information from clinical
ESR Values in Patients With RA
Wolfe F, Michaud K, J
Rheumatol. 1994;21:1227–1237.
Wichita
KS,
USA
ESR ≥ 28
ESR < 28
mm/h
mm/h
Females
63%
37%
Males
55%
45%
Similar results have been reported from:
Nashville, TN, USA
Jyvaskyla, Finland
Oslo, Norway
Nancy, France
Groningen, The Netherlands Belfast, Ireland
ESR in 7 Locations 1994-2005
% ESR<28
mm/Hr
1994
1996
1996
1556
F37%,M45%
237
135
26
1996
283
28
Belfast, N Ireland2
1996
Jyvaskyla, Finland 3 2009
Nashville, TN, USA3 2009
51
28
30
30
Wichita, KS, USA1
Oslo, Norway2
Nancy, France2
Groningen,
Netherlands2
Yr of
report
Mean Median
ESR (mm/h)
n
Location
1892
738
37F, 34M
29
45%
47%
1- Wolfe and Michaud, J Rheumatol. 1994;21:1227–1237.
2- Smedstad, Kvein, et al. Br J Rheumatol 1996;35:746-751.
3- Sokka T, Kauitinen, Pincus. J Rheumatol. 2009;36(1):1387-1390.
Meta-analysis:
Anti-cyclic citrullinated peptide (CCP)
antibody and rheumatoid factor (RF)
Anti-CCP
RF
Number of studies
37
50
Positive likelihood
ratio
12.5
4.9
Odds ratio for RA 16.1 – 39.0
1.2 – 8.7
Nishimura K et al. Annals of Internal Medicine 146:797-808, 2007
Meta-analysis: Anti-cyclic citrullinated peptide
(CCP) antibody and rheumatoid factor (RF)
Number of studies
Positive likelihood ratio
Anti-CCP
RF
37
50
12.5
4.9
Odds ratio for RA 16.1 – 39.0
1.2 – 8.7
Sensitivity
67%
69%
Specificity
95%
85%
% of patients with
negative test result
33%
31%
Nishimura K et al. Annals of Internal Medicine 146:797-808, 2007
% of RA patients with abnormal
measures at presentation:
Evidence – not eminence –
based
•
•
•
•
•
•
ESR >28 mm/Hr
CRP >10
Rheumatoid factor positive
Anti-CCP positive
Function score >2/10
Pain score >2/10
-
57%
58%
69%
67%
70%
89%
Wolfe F, et al. J Rheumatol. 1994;21:1227-37.
Sokka T, et al. J Rheumatol. 2009;36:1387-90.
Nishimura K, et al. Ann Intern Med. 2007;146:797-808.
Pincus T, Swearingen CJ. [Abstract #432] Arthritis Rheum 2009;60(Suppl):S160
Proposed Laboratory
Biomarkers for Rheumatoid
Arthritis Over 60 Years
1950s
1960s
1970s
1980s
1990s
2000s
Rheumatoid factor
Immune complexes
HLA type, Prostaglandins
Shared epitope
Monoclonal Abs,Anti-CCP
Genes, cytokine targets
•Of course, the laboratory remains
the primary source of further
understanding of pathogenesis
and advances in therapy.
•Nonetheless, for clinical care,
laboratory tests have substantial
limitations, including normal values
in 30-50% of individual patients with
many diseases, and often do not
change decisions about therapy.
Formal quantitative
joint count for a
rheumatology visit
checklist?
A simplified twenty-eightjoint quantitative articular
index in rheumatoid
arthritis
HA Fuchs, RH Brooks,
LF Callahan, T Pincus
Arthritis Rheum 32:531-537, 1989
Relative efficiencies of 7 ACR
Core Data Set measures in 4
adalimumab clinical trials
3.00
2.72
2.65
2.50
2.14
2.12
2.00
1.86
1.48
1.50
1.10
1.00
1.00
2.06
1.55
1.60
1.42
1.52
1.48
1.36
1.30
1.12
1.00
0.92
0.94
1.00
1.66
1.00
1.43
1.27
1.17
0.60
0.50
0.22
0.00
ARMADA
DE011
DE019
STAR
Tender Joint Count
Swollen Joint Count
Assessor Global
CRP
Function (HAQ)
Pain
Patient Global
Relative efficiencies of 7 Core Data Set measures and 3 Indices,
DAS28, CDAI, and RAPID3, to distinguish patients treated with
infliximab vs control therapies in ATTRACT and ASPIRE clinical trials
Furer, Pincus, et al, EULAR 2009
Changes in measures in 100 RA patients –
1985-1990 over 5 years - effect size
Type of measure:
Joint count
Radiographic
Laboratory
Clinical
Tenderness
Swelling
Pain on motion
Deformity
Limited motion
Joint space narrowing
Erosions
Malalignment
Erythrocyte sedimentation rate
Rheumatoid factor titer
Hemoglobin
Morning stiffness
Grip strength
Walk time
Button time
Functional status–MHAQ
Global status
Pain–visual analog scale
Helplessness
Better
Worse
Patient questionnaire
–1.5
–1.3
– 1.1 – 0.9 – 0.7 – 0.5 – 0.3 – 0.1 0.1
MHAQ=modified Health Assessment Questionnaire.
Callahan, Pincus et al. Arthritis Care Res
Effect Size
0.3
0.5
Some Limitations of Formal
Swollen and Tender Joint
Countsto distinguish
• Relative efficiencies
active from control treatments in
clinical trials are similar or lower
than global and patient measures
• May improve over 5 years while
joint deformity and functional
disability may progress
Joint counts in RA
• Of course, joint count is the most
specific measure of RA status.
• The most specific measure is not
necessarily most informative.
• Poorly reproducible by different
observers - must be done by same
observer – not GP, infusion, etc.
• Rigorous formal joint count not
performed at most visits
A careful joint
examination, rather
than a formal joint
count may be
appropriate for a
rheumatology visit.
Radiographs and
imaging studies for
a rheumatology
visit checklist?
Radiographs in Diagnosis and
Management of Patients With RA
• Excellent quantitative scoring
systems - Sharp, van der Heijde,
Larsen, Genant
• Erosions are closest to
pathognomonic sign in RA
• Reflect cumulative damage of
disease
Change from baseline (Mean +/- SE)
TEMPO Trial: Year 2 Radiograph:
Change in Total Sharp Score from
8
Baseline to Year 2
7
6
5
MTX = 206
E = 203
MTX+E = 213
3.34
(CI 1.18, 5.50)
4
3
2
1.10*
(CI 0.13, 2.07)
1
0
-1
* p < 0.05, E vs MTX
† p < 0.05, Combination vs MTX
‡ p < 0.05, Combination vs E
-0.56†‡
(CI –1.05, -0.06)
450
400
350
300
250
200
150
100
50
1
1.59
-0.54
ERA ETA
ERA MTX
TEMPO
Combi
0.52
2.8
0.4
3.7
1.3
3
5.7
IFX MTX
PREMIER
Combi
PREMIER
ADA
PREMIER
MTX
0
TEMPO ETA TEMPO MTX IFX Combi
Yazıcı Y, Yazıcı H, Arthritis Rheum 2006;54(supl)
Change in Total Sharp/van der Heijde radiographic
scores (0-448) in TEMPO trial over 2 years
Van der Heijde A&R2006
RA Cohort #2- Cox Proportional Hazards Model
Analyses Including Demographic, Functional, SelfReport, Joint Count, X-ray, Laboratory and Disease
Variables in 206 patients 1985-1990
Univariate
RR
P
(95% CL) Value
1.07
<0.001
Age
Stepwise Model
RR
P
(95% CL) Value
1.06
<0.001
Comorbidity
MHAQ ADL Score
Disease duration
Education
ESR
Joint count
1.63
2.00
1.04
0.89
1.01
1.02
<0.001
0.003
0.02
0.007
0.005
0.10
1.40
1.76
-----
Walking time
X-ray
1.03
1.40
0.04
0.17
---
Callahan, Brooks, Pincus, Arthritis Care Res 10:381,1997
0.02
0.02
-------
Significance of 8 variables as predictors of mortality in 53 RA cohorts
Significant in multivariate analyses
100%
6%
4%
22%
30%
Significant in univariate analyses
34%
17%
32%
23%
21%
39%
32%
46%
Not Significant
50%
39%
75%
50%
50%
28%
25%
72%
0%
65%
Physical
Cofunction morbidities
(N=18)
(N=23)
45%
44%
37%
31%
Rheumatoid
factor
(N=29)
Extraarticular
disease
(N=18)
ESR
(N=19)
Socioeconomic
status
(N=13)
22%
11%
Joint
count
(N=18)
Hand
radiograph
(N=18)
Sokka T, Abelson B, Pincus T. Clin Exp Rheumatol 26(suppl):S35-61, 2008
Associations of HLA-DR4 with
rheumatoid factor and
radiographic severity in
rheumatoid arthritis.
NJ Olsen, LF Callahan, RH Brooks,
EP Nance, JJ Kaye, P Stastny, T Pincus
Am J Med 84:257-264, 1988
Strongly and Weakly Related
Measures to Assess RA
Radiographs Functional disability
ESR, CRP Pain
Shared epitope Patient global
Joint swelling
Rheumatoid factor Joint tenderness
Joint deformity Fatigue
Duration of disease Age
MRI Can Better Identify Early Bone
Erosions than X-ray
Methotrexate in RA Care: 1980-2005
Jyvaskyla, Finland & Nashville, TN
Sokka and Pincus. Rheumatology (Oxford). 2008:47:1543-1547.
T Pincus, TWJ Huizinga, Y Yazici
J Rheumatol. 34:250-252, 2007
Some Problems With
Radiographs in RA
1. Quantitative score tedious to perform
2. Treatment initiated prior to erosions –
MRI, ultrasound more sensitive
3. Radiographic damage has poor
prognostic value for work disability,
death and even joint replacement
4. Treatment prior to erosions
Patient self-report
questionnaire
scores for a
rheumatology visit
checklist?
Patient self-report questionnaires
in usual rheumatology care
• Patient questionnaire provides
quantitative patient history
• Improvement in rheumatology
care cannot be documented
optimally without quantitative
patient self-report data
• Not having these data in most
settings is a major stumbling
block for rheumatology
MultiDimensional
Health
Assessment
Questionnai
re
(MDHAQ)
Page 1
MDHAQ/RAPID3:
04 Nov 2003
3 RA Core Data Set
scores
FN (0–10) = 2.7
PN (0–10) = 9.5
PTGL (0–10) = 9.0
2.7
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RAPID3 (0–30) = 21.2
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9.5

Severity:
12.1-30 = High
6.1-12 = Moderate
3.1-6 = Low
0-3 = Near remission
9.0
21.2
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Indices to assess patients with RA
ACR 1 DAS28 2 CDAI 3 RAPID3 4
# Tender joints
# Swollen joints
MD global
ESR or CRP
Patient function
Patient pain
Patient global
TOTAL
√
√
√
√
√
√
√
0.56 sq rt
(TJC28)
0.28sq rt
(SJC28)
-0.70 
ln (ESR)
--0.014 
PTGL
0-10
0-28
0-28
0-10
---0-10
0-76
----0-10
0-10
0-10
0-30
1. Felson DT, et al. Arthritis Rheum. 1993;36;729-49.
2. Prevoo MLL, et al. Arthritis Rheum 1995;38:44-8.
3. Aletaha D, Smolen J. Clin Exp Rheumatol 2005;23:S100-8.
4. Pincus T, et al. J Rheumatol. 2008;35: 2136-47.
DAS = Disease Activity Score, CDAI = Clinical Disease Activity Index.
Visit 1: 14 Nov 2003
Visit date
4Nov03
L-ESR
2.7
9.5
9.0
21.2
43
Prednisone
N-3qd
T-Methotrexate
N10qw
Q-Function (0–10)
Q-Pain (0–10)
Q-Global (0–10)
RAPID3 (0–30)
T-Folic acid
N1qd
T-Tylenol w/Codeine
30tid
T-Naproxen
880q6h
N=new medication, C=change in dose, T=taper, D/C=discontinue
RAPID3 versus DAS28 and CDAI
in 285 RA patients
DAS28
CDAI
Spearman correlation
Spearman correlation
rho = 0.657
rho = 0.738
Pincus T, et al. J Rheumatol. 2008; 35: 2136-2147.
150
Time to Score RA Measures Seconds
114
100
50
106
94
42
9.6
4.6
0
28 Joint HAQ-DI DAS28
Count
CDAI
RAPID3 RAPID3
(0-10) (0-30)
Pincus, Swearingen, Bergman, Colglazier, Kaell,
Kunath, Siegel, Yazici Arthritis Care Res. 2010; 62:181-189.
HAQ-DI = Health Assessment Questionnaire-Disability Index
MDHAQ/RAPID3:
04 Nov 2003
3 RA Core Data Set
scores
FN (0–10) = 2.7
PN (0–10) = 9.5
PTGL (0–10) = 9.0
2.7
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RAPID3 (0–30) = 21.2

9.5

Severity:
12.1-30 = High
6.1-12 = Moderate
3.1-6 = Low
0-3 = Near remission
9.0
21.2
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MDHAQ/RAPID3:
13 Jan 2004
3 RA Core Data Set
scores
FN (0–10) = 0
PN (0–10) = 0.5
PTGL (0–10) = 0.5
RAPID3 (0–30) = 1.0
0
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0.5

0.5
1.0
Severity:
12.1-30 = High
6.1-12 = Moderate
3.1-6 = Low
0-3 = Near remission
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Visit 2: 13 Jan 2004
Visit date
4Nov03
13Jan04
Q-Function (0–10)
2.7
0
Q-Pain (0–10)
9.5
0.5
Q-Global (0–10)
9.0
0.5
RAPID3 (0–30)
21.2
1.0
Tender Joint Count (0-28)
14
2
Swollen Joint Count (0-28)
12
1
MD Global (0-10)
8.0
1.0
43.0
4.5
43
8
N3qd
3qd
N10qw
C20qw
T-Folic acid
N1qd
1qd
T-Tylenol w/Codeine
30tid
30tid
880q6h
440bid
CDAI (0-76)
L-ESR
T-Prednisone
T-Methotrexate
T-Naproxen
T-Adalimumab
N = new drug, C = change in dose, T = taper, D/C = discontinue
Visit 4 - 28 Sep 2004
Visit Date
4Nov03
13Jan04
20Apr04
28Sep04
L-ESR
2.7
9.6
8.9
21.2
43
0
0.3
0.3
0.6
8
0.3
0.2
0.3
0.8
13
0
0.6
1.0
1.6
10
T-Prednisone
N3qd
3qd
3qd
3qd
N10qw
C20qw
20qw
15qw
T-Folic acid
N1qd
1qd
1qd
1qd
T-Tylenol w/Codeine
30tid
30tid
D/C
880q6h
440bid
440bid
Q-Function (0–10)
Q-Pain (0–10)
Q-Global (0–10)
RAPID3 (0–30)
T-Methotrexate
T-Naproxen
440bid
N = new drug, C = change in dose, T = taper, D/C = discontinue
MDHAQ/RAPID3:
28 Dec 2004
3 RA Core Data Set
scores
FN (0–10) = 0
PN (0–10) = 6.0
PTGL (0–10) = 5.5
0













6.0

RAPID3 (0–30) = 11.5
5.5
11.5
Severity:
12.1-30 = High
6.1-12 = Moderate
3.1-6 = Low
0-3 = Near remission



















MDHAQ/RAPID3:
28 Dec 2004
3 RA Core Data Set
scores
FN (0–10) = 0
PN (0–10) = 6.0
PTGL (0–10) = 5.5
0













6.0

RAPID3 (0–30) = 11.5
5.5
11.5
Severity:
12.1-30 = High
6.1-12 = Moderate
3.1-6 = Low
0-3 = Near remission



















Visit 5: 28 Dec 2004
Visit date
4Nov03
13Jan04
20Apr04
28Sep04
28Dec04
Q-Function (0–10)
2.7
0
0.3
0
0
Q-Pain (0–10)
9.5
0.5
0.0
0.5
6.0
Q-Global (0–10)
9.0
0.5
0.5
1.0
5.5
RAPID3 (0–30)
21.2
1.0
0.8
1.5
11.5
Tender Joint Count (0-28)
14
2
0
0
10
Swollen Joint Count (0-28)
12
1
0
0
8
MD Global (0-10)
8.0
1.0
0.5
0.5
6.5
43.0
4.5
1.0
1.5
30.0
43
8
13
10
14
N3qd
3qd
3qd
3qd
3qd
N10qw
C20qw
20qw
15qw
C25qw
T-Folic acid
N1qd
1qd
1qd
1qd
1qd
T-Tylenol w/Codeine
30tid
30tid
D/C
880q6h
440bid
440bid
440bid
440bid
CDAI (0-76)
L-ESR
T-Prednisone
T-Methotrexate
T-Naproxen
T-Adalimumab
N=new drug, C=change in dose, T=taper, D/C=discontinue
N40qow
MDHAQ/RAPID3:
8 Feb 2005
3 RA Core Data Set
scores
FN (0–10) = 0
PN (0–10) = 0.0
PTGL (0–10) = 0.5
RAPID3 (0–30) = 0.5
0













0

0.5
0.5
Severity:
12.1-30 = High
6.1-12 = Moderate
3.1-6 = Low
0-3 = Near remission



















Visit 6: 8 Feb 2005
Visit date
4No03
13Ja04
20Ap04
28Se04
28De04
8Fe05
2.7
0
0.3
0
0
9.5
9.0
21.2
0.5
0.5
1.0
0.0
0.5
0.8
0.5
1.0
1.5
6.0
5.5
11.5
43
8
13
10
14
0
0.0
0.5
0.5
14
N3qd
3qd
3qd
3qd
3qd
3qd
N10qw
C20qw
20qw
15qw
C25qw
C15qw
T-Folic acid
N1qd
1qd
1qd
1qd
1qd
1qd
T-Tylenol w/Codeine
30tid
30tid
D/C
880q6h
440bid
440bid
440bid
440bid
D/C
N40qow
40qow
Q-Function (0–10)
Q-Pain (0–10)
Q-Global (0–10)
RAPID3 (0–30)
L-ESR
T-Prednisone
T-Methotrexate
T-Naproxen
T-Adalimumab
N=new drug, C=change in dose, T=taper, D/C=discontinue
Cross-Sectional Data in Patients With RA –
Cohort #2 in 1985 and Cohort #4 in 2000:
Multidimensional Health Assessment Questionnaire
(MDHAQ) scores
2000
2.0
2.0
1.5
1.5
MHAQ
MHAQ
1985
1.0
1.0
0.5
0.5
0.0
0.0
0
5
10
15
Disease Duration (Years)
20
0
5
10
15
20
Disease Duration (Years)
Pincus, Sokka, Kautiainen, Arthritis Rheum 52:1009, 2005
Cross-Sectional Data in Patients With RA –
Cohort #2 in 1985 and Cohort #4 in 2000:
Swollen Joint Count Scores
1985
2000
20
Swollen Joint Count 28
Swollen Joint Count 28
20
16
12
8
4
0
16
12
8
4
0
0
5
10
15
Disease Duration (Years)
20
0
5
10
15
20
Disease Duration (Years)
Pincus, Sokka, Kautiainen, Arthritis Rheum 52:1009, 2005
25
RF+
20
15
10
5
0
0
5
10
Disease duration
15
Larson score for hands, % of max
Larson score for hands, % of max
Patients –
Cohort #2 in 1985 and Cohort #4
in 2000: Larsen X-Ray score,% of
1985
2000
Maximum
30
30
RF25
20
RF+
15
10
5
RF-
0
0
5
10
15
Disease duration
Pincus, Sokka, Kautiainen, Arthritis Rheum 52:1009, 2005
Median Levels of All Patients at Initiation of MTX
1996-2001 and Mean of 2.6 Years Later in:
A. 63 “control” adequate responders continuing MTX
B. 30 incomplete responders initiating biologic agent
63 Adequate
Responders (“Controls”)
ESR
30 Incomplete
Responders
Biologic
Follow-up
MTX Start (NO Biologic) MTX Start
Start
24
16
28
18
MDHAQ-Function
2.3
1.0
3.2
3.3
Pain
4.1
1.4
5.2
6.8
Patient Global
4.2
0.9
5.5
5.5
RAPID3
10.6
3.6
14.9
16.2
Pincus T, Swearingen CJ. [Abstract #1627] Arthritis Rheum 2009;60(Suppl):S608.
Presented at ACR, 2009.
The HAQ or MDHAQ, not a joint count, lab
test or X-ray, 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 & 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 & Zwillich Arthritis Rheum 1998)
• Death
(Pincus et al Arthritis Rheum 1984, Ann Intern Med 1994;
Wolfe et al J Rheumatol 1988, Arthritis Rheum 1994;
Leigh & Fries J Rheumatol 1991; Callahan et al Arthritis Care Res
1996, 1997; Soderlin et al J Rheumatol 1998; Maiden et al Ann
9-10 Year Survival According to Quantitative Markers
in Three Chronic Diseases
Rheumatoid Arthritis Activities of Daily Living
A
Rheumatoid Arthritis -
B
>90%
81–90%
80
% Active “With Ease”
60
40
71–80%
Survival (%)
Survival (%)
100
>12 Years
80
9–12 Years
60
8 Years
40
20
70%
20
Formal Education Level
100
(Data from Pincus et al, 1987)
(Data from Pincus et al, 1987)
20
60
80
100
100
Stage I
80
Stage II
Stage III All Stages,
All Causes
Stage IV
60
40
0
Months
Hodgkin’s Disease Anatomic Stage
C
Survival (%)
40
20
D
0
2
4
6
8
10
Years
40
60
80
100
Months
Coronary Artery Disease # of Involved Vessels
80
60
40
20
(Data from Kaplan, 1972)
20
100
Survival (%)
0
1 Artery
2 Arteries
3 Arteries
LCA
(Data from Proudfit et al, 1978)
0
2
4
6
8
10
Years
5-Year Survival in 206
Patients With RA: Cohort #2 –
1985-1990
Rheumatoid Factor
MHAQ Score
80
80
Survival (%)
100
Survival (%)
100
60
60
40
Absent (29)
Present
20
(175)
0.00 (12)
0.01–0.99 (91)
1.00–1.99 (86)
>2.00 (21)
40
20
0
0
0
12
24
36
48
Months After Baseline
60
0
12
24
36
48
Months After Baseline
Callahan LF et al. Arthritis Care Res 10:381,1997
60
Significance of 8 variables as predictors of mortality in 53 RA cohorts
Significant in multivariate analyses
100%
6%
4%
22%
30%
Significant in univariate analyses
34%
17%
32%
23%
21%
39%
32%
46%
Not Significant
50%
39%
75%
50%
50%
28%
25%
72%
0%
65%
Physical
Cofunction morbidities
(N=18)
(N=23)
45%
44%
37%
31%
Rheumatoid
factor
(N=29)
Extraarticular
disease
(N=18)
ESR
(N=19)
Socioeconomic
status
(N=13)
22%
11%
Joint
count
(N=18)
Hand
radiograph
(N=18)
Sokka T, Abelson B, Pincus T. Clin Exp Rheumatol 26(suppl):S35-61, 2008
Prediction of premature
mortality according to blood
pressure and cholesterol
converted hypertension and
hypercholesterolemia from
optional treatments to major
public health campaigns.
Patient and
physician global
estimates for a
rheumatology visit
checklist?
Relative efficiencies of 7 ACR
Core Data Set measures in 4
adalimumab clinical trials
3.00
2.72
2.65
2.50
2.14
2.12
2.00
1.86
1.48
1.50
1.10
1.00
1.00
2.06
1.55
1.60
1.42
1.52
1.48
1.36
1.30
1.12
1.00
0.92
0.94
1.00
1.66
1.00
1.43
1.27
1.17
0.60
0.50
0.22
0.00
ARMADA
DE011
DE019
STAR
Tender Joint Count
Swollen Joint Count
Assessor Global
CRP
Function (HAQ)
Pain
Patient Global
A proposed checklist of 10 measures for
patients with rheumatic disease at all visits
Patient MDHAQ self-report questionnaire
measures
1. Function
2. Pain
3. Patient global estimate of status
4. RAPID3 (Routine Assessment of Patient
Index Data)
5. Fatigue
6. Symptoms
MDHAQ:
Page 1 of 2
1. a - j:
Physical
function
k, l, m:
Psychological
distress
2. Pain
3. RADAI
Self-report
joint count
4. Patient
global
estimate
RAPID3
MDHAQ:Page 2
5. Review of
systems
6. Morning
stiffness
7. Change in
status
8. Exercise
9. Fatigue
10.Recent
medical
history
11.Demographic data
MD review
Review of Symptoms (ROS)














Quantitative patient MDHAQ scores in new
rheumatology patients by diagnosis
RA
OA
FM
SLE Spondy Gout
(n=174) (n=32) (n=196) (n=34) (n=30) (n=12)
Function [0-10]
3.2
2.3
3.0
1.9
3.0
1.8
Pain [0-10]
5.4
4.4
6.5
3.7
5.9
5.8
PT Global [0-10]
5.4
4.4
6.1
4.3
5.1
3.8
RAPID3 [0-30]
13.7
10.0
15.4
8.5
13.4
10.2
Fatigue [0-10]
5.7
4.2
7.3
5.4
4.5
4.1
14.1
9.4
20.5
16.1
11.4
7.7
Symptoms [0-60]
FM = fibromyalgia; Spondy = spondylarthropathy.
Shaded: Patient measures: FN>3, PN5, PTGL5, FT5, RAPID3>12, SX>20.
Quantitative demographic and laboratory data
in new rheumatology patients by diagnosis
RA
OA
FM
SLE Spondy Gout
(n=174) (n=32) (n=196) (n=34) (n=30) (n=12)
54.5
65.1
47.0
38.8
43.9
59.3
Disease duration
(years)
8.4
6.3
5.9
9.1
11.3
9.1
Formal education
(years)
13.0
15.0
13.7
13.6
14.9
13.8
Age (years)
% Female
71.3% 65.6% 88.7% 85.3% 46.7% 16.7%
ESR (mm/h)
29.7
22.2
16.8
28.9
26.5
11.1
CRP (mg/dL)
[normal <10]
17.5
3.9
6.1
6.7
11.5
3.6
FM = fibromyalgia; Spondy = spondylarthropathy.
Shaded: ESR >20, CRP >10.
Highest ranked source of clinical information 588
>50%:
20-50%:
<20%:
MDs:
Element
Cong
Heart
Failure
Diabetes
Melllitus
Hypertension
Hyperlipidemia
Lymphoma
Pulmonary
Fib
Vital
Signs
Patient
History
Physical
Exam
Lab
tests
Other
studies
McCollum, Durusu Tanriover, Akalžn ,
H Yazici, Pincus: EULAR 2010
Rheumat
Arthritis
UlcerativeC
oli-tis
A proposed checklist of 10 measures for
patients with rheumatic disease at all visits
Patient MDHAQ self-report questionnaire measures
1. Function
2. Pain
3. Patient global estimate of status
4. RAPID3 (Routine Assessment of Patient Index Data)
5. Fatigue
6. Symptoms
Physician global measures
7. Physician global estimate of status (DOC Global)
8. Inflammation
9. Damage
10. Non-inflammatory/non-damage
4 Physician global estimates:
1.Overall, 2. Inflammation,
3. Damage, 4. Neither
The expertise of a rheumatologist is to
determine whether a patient’s pain, fatigue,
distress, etc. results from inflammation,
damage or neither. Why not record scores?
Quantitative physical
examination data in RA
• Joint count required for RA
diagnosis
• Joint count is most specific RA
measure
• Joint count has many limitations
• Physician global estimates perform
as well as formal joint counts to
distinguish active from control
treatment in clinical trials
Quantitative physician global estimates in
new patients by diagnosis – T Pincus
RA
OA
FM
SLE Spondy Gout
(n=174) (n=32) (n=196) (n=34) (n=30) (n=12)
DOC Global [0-10]
6.3
6.3
6.3
5.0
6.3
5.0
Inflammation [0-10]
7.0
3.3
2.3
3.6
7.7
6.0
Damage [0-10]
5.0
6.0
1.7
2.3
4.3
3.0
Non-inflammatory/
non-damage [0-10]
4.0
3.7
9.0
6.3
4.0
2.3
FM = fibromyalgia
Spondy = spondylarthropathy
Shaded: All DOC measures 5
Quantitative physician global estimates in
new patients by diagnosis – M Bergman
Variable
RA
OA
FM
SLE Spondy Gout
Overall Physician
Global (0-10)
4.03
3.25
4.36
2.00
3.33
2.23
Inflammation
(0-10)
4.53
0.57
0.50
2.23
4.17
2.27
Damage
(0-10)
2.40
3.83
0.77
0.37
1.58
0.43
Non-inflammatory,
Non-damage (0-10)
1.03
0.83
5.13
0.37
1.17
0.43
FM = fibromyalgia
Spondy = spondyloarthropathy
Shaded = highest-scored scale for each diagnostic category
Quantitative patient MDHAQ scores and physician global
estimates in new rheumatology patients by diagnosis
RA
OA
FM
SLE Spondy Gout
(n=174) (n=32) (n=196) (n=34) (n=30) (n=12)
Patient MDHAQ self-report questionnaire measures for proposed checklist
Function [0-10]
Pain [0-10]
PT Global [0-10]
RAPID3 [0-30]
Fatigue [0-10]
Symptoms [0-60]
3.2
5.4
5.4
13.7
5.7
14.1
2.3
4.4
4.4
10.0
4.2
9.4
3.0
6.5
6.1
15.4
7.3
20.5
1.9
3.7
4.3
8.5
5.4
16.1
3.0
5.9
5.1
13.4
4.5
11.4
1.8
5.8
3.8
10.2
4.1
7.7
5.0
3.6
2.3
6.3
6.3
7.7
4.3
4.0
5.0
6.0
3.0
2.3
Physician global measures for proposed checklist
DOC Global [0-10]
Inflammation [0-10]
Damage [0-10]
Non-inflam/non-damage [0-10]
6.3
7.0
5.0
4.0
6.3
3.3
6.0
3.7
6.3
2.3
1.7
9.0
FM = fibromyalgia; Spondy = spondylarthropathy. Shaded: Patient measures: FN>3,
PN5, PTGL5, FT5, RAPID3>12, SX>20. All DOC measures 5.
Scientific method in medical care:
standardized measurement is
prerequisite
• All rheumatology clinical measures
are surrogates for pathogenic
mechanisms – whether ESR, joint
counts, or self-report questionnaire
scores.
• All measures require interpretation
by a knowledgeable and caring
physician.
Is this the final version of a
rheumatology visit
checklist?
No, it will be improved by
suggestıons from
rheumatologists like you
from use in clinical care.
Is it better to have 80% of the
information in 100% of patients
or 100% of the information in
5% of patients?
T Pincus, F Wolfe
J Rheumatol 32:575-577, 2005
Is care for a patient without a
HAQ/MDHAQ/RAPID 3,
analogous to care of a patient
with hypertension without a
blood pressure, or care of a
patient with diabetes without
hemoglobin A1C or glucose?