Transcript Slide 1

Measures in RA: Joint counts,
radiographs, laboratory tests,
patient questionnaires advantages and disadvantages
[email protected]
Disclosures
Theodore Pincus, MD
Sources of Funding for Research: Amgen Inc.; BristolMyers Squibb Company
Consulting Agreements: Abbott Laboratories; Amgen
Inc.; Bristol-Myers Squibb Company; UCB
Speakers’ Bureau/Honorarium Agreements: Abbott
Laboratories; Wyeth Pharmaceuticals, Genentech
Financial Interests/Stock Ownership: None
Discussion of Off-Label, Investigational, or
Experimental Drug Use: None
It’s all about
measurement

“When you can measure what
you are speaking about, and
express it in numbers, you
know something about it; but
when you cannot measure it
[and] express it in numbers,
your knowledge is of a meager
and unsatisfactory kind.”
Lord Kelvin – quoted by:
Buchanan W, Smythe H.
J Rheumatol. 1982:9;653–4.
Prevailing view of
rheumatoid arthritis - 1984:
“Patients with rheumatoid
arthritis usually respond to a
conservative program of
nonsteroidal anti-inflammatory
drugs, rest, and physical
therapy…”
Arthritis & Rheumatism 27:1344,1984
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
observational data in addition to clinical trials
Pincus and Tugwell J Rheumatol 2006
Rheumatoid arthritis:
disappointing long-term
outcomes despite
successful short-term
clinical trials
T Pincus
J Clin Epidemiol 41(11):1037-1041, 1988
Some Pragmatic Limitations of Randomized
Controlled Clinical Trials in Chronic Diseases
J Clin Epidemiol 41:1037,1988; Arthritis Rheum 48:313, 2003
1.Relatively short observation period
2. Inclusion and exclusion criteria - most
patients ineligible in most trials
3. Surrogate markers - may be
suboptimal for actual outcomes, e.g., T
cell counts vs. AIDS, tender joints vs.
surgical replacement
4. Inflexible dosage schedules and
concomitant drug therapies
Standard Composite Treatment Effect*
Effect in Standard Units
2
1.5
1
0.5
0
(n=28) (n=25) (n=11) (n=15) (n=28) (n=9)
Plac
AUR AntiM AZA
Gold MTX
(n=22)
DPen
(n=8)
SSZ
<.0001
<.0001
<.05
*Composite of grip strength(adjust for disease duration and trial length),
tender joint count (adjust for initial TJC and blinding) and ESR
Felson, Anderson, Meenan. Arthrit Rheum. 1990;33:1449.
Estimated Continuation
Estimated Continuation of Courses of 2nd Line Therapies
Over 60 Months in RA Patients
Azathioprine (56)
Hydroxychloroquine (228)
Methotrexate (253)
Oral gold (84)
Parenteral gold (269)
Penicillamine (193)
1.0
0.8
0.6
0.4
0.2
0
0
10
20
30
40
50
60
Months
Pincus, Marcum, Callahan. J Rheumatol. 1992;19:1885.
RA Cohort #2-15 US sites 1985-90
Participating Rheumatologists
•
•
•
•
•
•
•
•
F. Adams
J. Barber
W. Barth
M. Britton
G. Gordon
J. Huston
J.T. John
J. Johnson
TN
CA
DC
CA
PA
TN
TN
TN
•
•
•
•
•
•
•
A. Kennedy FL
R. Polk
ID
J. Raitt
CA
J. ReinertsenMN
E. Schned MN
J. Sergent TN
A. Whelton FL
Estimated Continuation of Courses of 2nd-Line
Therapy
Azathioprine (56)
Hydroxychloroquine (228)
Methotrexate (253)
Oral gold (84)
Parenteral gold (269)
Penicillamine (193)
100
80
60
40
20
0
0
10
20
30
Months
40
50
60
Estimated Continuation (%)
Estimated Continuation (%)
All Courses Over 60 Months Initial Course Over 12 Months
10
0
8
0
6
0
4
0
Methotrexate (61)
Hydroxychloroquine
(130)
Penicillamine (55)
Parenteral gold (207)
Oral gold (5)
Azathioprine (19)
2
0
0
0
1
2
3
4
5
6
7
Months
8 9 10 1
1
Pincus, Marcum, Callahan. J Rheumatol. 1992;19:1885.
1
2
Severe functional declines,
work disability, and
increased mortality rates in
seventy-five rheumatoid
arthritis patients studied
over nine years
T Pincus, LF Callahan, WG Sale,
AL Brooks, LE Payne, WK Vaughn
Arthritis Rheum 27:864-872, 1984
Survival in rheumatoid arthritis 1973-1982
Pincus et al. Arthritis Rheum. 1984;27:864. J Rheumatol 1987;14:240
Survival of Patients With
Rheumatoid Arthritis Versus
Expected Survival in 10 Locales
Expected for
women
Expected for men
Women with RA
Men with RA
40
0
0 2 4 6 8 10
Years
60
40
0
Vandenbroucke et al, 1984 Mutru et al, 1985
Netherlands
Finland
100
5 10 15 20 25
Years
“definite” RA
40 Patients with
“classic” RA
0
Mitchell et al, 1986 Vollertsen et al, 1986
Minnesota
Saskatchewan
100
80
80 Expected
60 Expected for women
for women
for men
Expected for men
40 Expected
Women with RA
60 Women with RA
20 Men with RA
Men with RA
0
0
2 4 6 8 10
5 10 15
Years
Years
Survival (%)
Survival (No.)
Survival (%)
100
80
60
40 Expected for
Expected for women
men
20 Women with RA
Men with RA
0
5 10 15 20 25
Years
Women with OA
Men with OA
Women with RA
Men with RA
100
80
60 Patients with
Survival (%)
60
Survival (%)
80
100
80
60 Expected for women
40 Expected for men
with RA
20 Women
Men with RA
0
5
10
Years
Rasker and Cosh, 1981
England
1.00
0.80
0.60
0.40
0.20
0
Expected for
population
Patients with
“classic” RA
4 8 12 16 20
Years
4 8 1216 20 24
Years
Pincus et al, 1987
Tennessee
100
80
60
40
20
0
Survival (%)
10 20 30
Years
100
80
Probability
0
100
Survival (%)
1000
800
600 Expected for
400 population
200 Patients with RA
Monson and Hall, 1976 Allebeck et al, 1981
Massachusetts
Sweden
Uddin et al, 1970
Ontario
Survival (%)
Survival (No.)
Cobb et al, 1953
Massachusetts
Expected for women
Expected for men
Women with RA
Men with RA
5
Years
10
Attributed Causes of Death in 2,262 RA
Patients in 13 Series from Diverse Locales
Compared to General Population
Attributed Cause of Death
Cardiovascular disease
Cancer
Infection
Renal disease
Pulmonary disease
RA
GI disease
CNS disease
Accidents
Miscellaneous
Unknown
% of RA Deaths
42.1
14.1
9.4
7.8
7.2
5.3
4.2
4.2
1.0
6.4
0.6
% of 1977 US Deaths
41.0
20.4
1.0
1.1
3.9
<1
2.4
9.6
5.4
15.2
<1
Pincus T, Callahan LF. J Rheumatol. 1986;13:841.
9- to 10-Year Survival According to Quantitative
Markers in Three Chronic Diseases
A
Rheumatoid Arthritis – Activities of Daily Living
B
100
>90%
81%–90%
80
% Active “With Ease”
60
40
71%–80%
70%
20
Survival (%)
Survival (%)
100
Rheumatoid Arthritis – Formal Education Level
>12 Years
80
9–12 Years
60
8 Years
40
20
(Data from Pincus et al, 1987)
(Data from Pincus et al, 1987)
Months
0
40
60
80
100
Hodgkin Disease – Anatomic Stage
100
0
D
Stage I
80
60
Stage II
All Stages,
All Causes
Stage III
Stage IV
40
20
(Data from Kaplan, 1972)
0
2
4
6
Years
8
10
Survival (%)
Survival (%)
C
20
Months
20
40
60
80
100
Coronary Artery Disease – No. of Involved Vessels
100
80
1 Artery
60
2 Arteries
40
3 Arteries
LCA
20
(Data from Proudfit et al, 1978)
0
2
4
6
8
Years
10
Why Include Quantitative
Measurement in Care of Patients
with Rheumatic Diseases?
 Assess Prognosis – guides general
approach to therapy
 Treatment Decisions – specific
agents, changes
 Documentation – from visit to visit,
compare patients
 Reimbursement –value of treatment
by rheumatologist
Examples of measures that
convey prognostic significance






Blood pressure 220/140
Total cholesterol 528
Creatinine 20
Glucose 785
ESR 110
CCP >100 units
Complexities in assessment of
patients with rheumatic diseases:
1.
2.
3.
No single “gold standard” (eg, blood
pressure, cholesterol) for clinical trials
or standard care: therefore, indices of 37 measures.
Laboratory tests limited in both
diagnosis and treatment - primary
criteria are clinical.
Patient questionnaires to assess
physical function, pain, global status,
often best quantitative measures.
American College of Rheumatology (ACR)
Core Data Set & Disease Activity Score (DAS)
3 Physician/Assessor measures
1. Tender joint count (also in DAS)
2. Swollen joint count (also in DAS)
3. Assessor Global status
3 Patient self-report measures
4. Physical Function - HAQ, HAQ II, MDHAQ
5. Pain
6. Patient Global status (also in DAS)
1 Laboratory Measure
7. Acute phase reactant –ESR, CRP–also in DAS
(8. Radiograph – longer than 1 year)
Felson et al, Arth Rheum 36:729, 1993. van Riel, Br J Rheumatol 31:793, 1994.
Types of Measures to Assess RA
Joint count
Radiograph
Laboratory tests
Patient self-report questionnaires
Formal Joint Counts in
Management of Patients With RA
 Most specific measure to assess RA
 Most important measure in clinical
trials – 20, 50, 70% required for ACR
improvement criteria
 28-joint count as useful in clinical
trials as 68–70 joint counts
Some Limitations of Formal Joint Counts
 Joint counts have similar or lower
relative efficiencies than global and
patient measures to document
differences between active and
control treatments in clinical trials
(Arthritis Rheum 48:625-630, 2003.
Arthritis Rheum 52:1031-1036, 2005.
J Rheumatol 33:2146-2152, 2006,
Rheumatology, in press)
Some Limitations of Formal Joint Counts
 Joint counts may improve over 5
years while progressive joint
damage and functional disability
may occur
(Callahan et al, Arthritis Care Res
10:381-394, 1997)
Some Limitations of Formal Joint Counts
Joint counts are poorly
reproducible






Lewis et al. Br J Rheumatol 1988; 27:32.
Hart et al. J Rheumatol 1985; 12:716.
Klinkhoff et al. J Rheumatol 1988; 15:492.
Thompson et al. J Rheumatol 1991; 18:661.
Kvien et al. Ann Rheum Dis 2005; 64:1480.
Scott DL et al. 2006; 15:579.
Some Limitations of Formal Joint Counts
 Rheumatologists perform careful
non-quantitative joint examination,
but not formal joint count, at most
visits in usual care
(Pincus and Segurado, Ann Rheum Dis
65:820-822, 2006.)
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%
1–24% of visits
25–49% of visits
50–74% of visits
75–99% of visits
Always
32%
11%
14%
16%
14%
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)
1985
30
RF-
25
RF+
20
15
10
5
0
0
5
10
Disease duration
15
2000
Larson score for hands, % of max
Larson score for hands, % of max
Cross-Sectional Data in RA Patients:
Cohort #2- 1985 and Cohort #4-2000:
Larsen X-Ray score,% of maximum
30
25
20
RF+
15
10
RF
55
positive
RF-
0
00
0
5
10
15
Disease duration
Pincus, Sokka, Kautiainen, Arth Rheum 52:1009, 2005
Predicting Mortality in RA: Most Baseline
Measures Are Worse in Patients Who Will
Die Over a 5-Year Period
Mean Baseline Values
P Value
Alive
Dead
Age (years)
ARA functional class
Number of comorbidities
Walking time
ESR
mHAQ score
Learned helplessness
Global self-report
Number of extra-articular features
Duration of disease
Years of education
Joint count
55.1
2.2
1.1
10.8
33.8
1.98
2.41
2.6
0.2
9.1
10.8
12.8
65.5
2.6
2.1
16.8
48.3
2.32
2.55
3.0
0.5
12.7
9.4
15.9
< 0.001
< 0.001
< 0.001
< 0.001
0.004
0.005
0.007
0.01
0.02
0.03
0.03
0.04
Radiograph score
RF titer
Pain
1.2
2.7
5.40
1.4
2.9
5.19
0.20
0.28
0.68
Callahan LF, et al. Arthritis Care Res. 1997;10:381–394.
RA Cohort #2- Cox Proportional Hazards Model
Analyses Including Demographic, Functional, SelfReport, Joint Count, X-ray, Laboratory and Disease
Variables in 206 patients
Age
Univariate
RR
P
(95% CL) Value
1.07
<0.001
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
---
Arthritis Care Res 10:381,1997
0.02
0.02
-------
Predictors of mortality in RA n=1922
Odds Ratio
HAQ
2.93
Pt Global severity
1.28
Pain
1.25
Depression
1.34
Anxiety
1.28
Grip strength
1.01
ESR
1.01
RF, titer
1.13
Hematocrit
1.06
Larsen X-ray score 1.04
Duration
1.01
Joint count
1.01
Age
Comorbidities
Male
1.09
1.19
2.10
z score p value
11.1
<0.001
8.5
<0.001
8.3
<0.001
8.8
<0.001
7.2
<0.001
6.2
<0.001
5.7
<0.001
4.6
<0.001
3.8
<0.001
4.7
0.002
2.1
0.036
0.76
0.445
11.9
4.69
5.28
<0.001
<0.001
<0.001
Wolfe et al Arth Rheum 48:1530, 2003
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 and Hawley. J
Rheumatol. 1998, Fex et al. J Rheumatol 1998, Sokka et
al. J Rheumatol 1999, Barrett et al. Rheumatology 2000,
Puolakka et al. Ann Rheum Dis 64:130-133, 2005 )
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)
Some Problems With
Radiographs in RA
1. Quantitative score tedious to
perform
2. Treatment initiated prior to erosions
– MRI, ultrasound are more
sensitive
3. Radiographic damage has poor
prognostic value for work disability,
death and even joint replacement
Laboratory Tests in Diagnosis and
Management of Patients With RA
1. Most important measure in most
clinical situations, e.g.,
cholesterol, hemoglobin,
creatinine, glucose, etc.
2. Many tests may be of value –
CBC, ESR, CRP, RF, anti-CCP
3. No work for the rheumatologist
ESR Values in Patients With RA
ESR ≥ 28
mm/h
ESR < 28
mm/h
Females
63%
37%
Males
55%
45%
Wolfe F, Michaud K, J Rheumatol. 1994;21:1227–1237.
ESR and CRP at 1st Visit to Clinic
a. Jyvaskyla, FIN
CRP
ESR
≥28 mm/hr <28 mm/hr
Total
>10 mg/L
775 (44%)
202 (12%)
<10 mg/L
199 (11%)
568 (33%)
Total
974 (55%)
770 (45%)
b. Nashville, TN, USA
CRP
ESR
≥28 mm/hr <28 mm/hr
977 (56%)
767 (44%)
1744 (100%)
>10 mg/L
<10 mg/L
Total
70 (41%)
100 (59%)
170 (100%)
48 (28%)
29 (17%)
77 (45%)
22 (13%)
71 (42%)
93 (55%)
Total
Sokka and Pincus, EULAR 2006
The level of inflammation in
rheumatoid arthritis is
determined early and remains
stable over the longterm course
of the illness
F Wolfe, T Pincus
J Rheumatol 28:1817-1824, 2001
Some Problems With Laboratory Tests in
Diagnosis and Management of RA
1. ESR & CRP - normal in 40% at
presentation
2. Anti-CCP & RF - negative in 20–50% of
patients
3. Treatment decisions are based primarily
on clinical criteria
4. Lab tests have good prognostic value for
radiographic damage but poor prognostic
value for work disability or death
CRP = C-reactive protein; CCP = cyclic citrullinated protein
Limitations of individual measures in RA:
need for an index for patient assessment
ACR
DAS28 CDAI
Core
# Tender joints
√
√
√
# Swollen joints
√
√
√
MD global
√
√
ESR or CRP
√
√
-Patient function
√
--Patient pain
√
--Patient global
√
√
√
Disease Activity Score (DAS)
in Rheumatoid Arthritis
Based on score on visits with DMARD change:
0.56 X square root (tender joint count 28) +
0.28 X square root (swollen joint count 28) +
0.70 X log e (ESR) +
0.014 (patient assessment of global status or
activity)
Total DAS= 0-10
Van der Heijde et al, J Rheumatol 20:579,1993,
Prevoo et al, Arthritis Rheum 38:44, 1995.
DAS28 Categories – Activity Level
Fransen and van Riel
Clin and Exp Rheumatol, 2005
Level
0–2.6
=
2.6–3.19 =
3.2–5.1 =
Interpretation
Remission – therapy is working
Low – maybe change therapy
Moderate – consider strongly
change in therapy
5.11–10 = High – change therapy or
have a good reason not to do so
Some Limitations of DAS
1. Requires complex math – need
calculator or website
2. Requires laboratory tests – often
uninformative or unavailable
3. Requires formal quantitative joint
count – often not done, poorly
reliable
Clinical Disease Activity Index (CDAI)
Aletaha and Smolen
Clin Exp Rheumatol 23:S100, 2005.
No lab test or complex math
Can be calculated in usual care
Tender joint count 28
Swollen joint count 28
Patient global assessment
Patient global assessment
Total CDAI
=
=
=
=
=
28
28
10
10
0-76
CDAI Categories – Activity Level
Aletaha and Smolen, 2005
Level
Interpretation
0–2.8
= Remission – therapy is working
2.81–10 = Low – maybe change therapy
10.1–22 = Moderate – consider strongly
change in therapy
22–76 = High – change therapy or
have a good reason not to do so
CDAI Overcomes 2 of 3
Limitations of DAS
1. No complex math
2. No laboratory test
3. But… requires formal quantitative
joint count
Is it possible to develop
index to assess patients
with RA (and other
rheumatic diseases) that
does not require a formal
quantitative joint count?
Limitations of individual measures in RA:
need for an index for patient assessment
ACR DAS28 CDAI
# Tender joints
√
√
√
# Swollen joints
√
√
√
MD global
√
√
ESR or CRP
√
√
-Patient function
√
--Patient pain
√
--Patient global
√
√
√
RAPID3
----√
√
√
Multidimensional Health Assessment Questionnaire
AT THIS MOMENT, are you able to:
Dress yourself, including tying shoelaces and
doing buttons?
Get in and out of bed?
Lift a full cup or glass to your mouth?
Walk outdoors on flat ground?
Wash and dry your entire body?
Bend down to pick up clothing from the floor?
Turn regular faucets on and off?
Get in and out of a car, bus, train or airplane?
Walk two miles?
Participate in sports and games as you would like?
Get a good night’s sleep?
Deal with feelings of anxiety or being nervous?
Deal with feelings of depression or feeling blue?
Without ANY
Difficulty
With SOME
Difficulty
With MUCH
Difficulty
UNABLE
To Do
----------------------------------------
----------------------------------------
----------------------------------------
----------------------------------------
How much pain have you had because of your condition IN THE PAST WEEK?
Place a mark on the line below to indicate how severe your pain has been:
NO
PAIN
                    
0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10
PAIN AS
BAD AS IT
COULD BE
Considering all the ways in which your illness and and health conditions
may affect you at this time, place a mark to show how you are doing:
VERY
WELL
                    
0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10
VERY
POORLY
Routine Assessment of Patient
Index Data (RAPID3) Score:
3 Patient Core Data Set Measures
on HAQ and MDHAQ
Physical function + 0-10
Pain = 0-10
Patient global estimate = 0-10
Total = 0-30 divide by 3 = 0-10
9- to 10-Year Survival According to
Quantitative Markers in Three Chronic
Diseases
A
Rheumatoid Arthritis – Activities of Daily Living
B
100
>90%
81%–90%
80
% Active “With Ease”
60
40
71%–80%
70%
20
Survival (%)
Survival (%)
100
Rheumatoid Arthritis – Formal Education Level
>12 Years
80
9–12 Years
60
8 Years
40
20
(Data from Pincus et al, 1987)
(Data from Pincus et al, 1987)
Months
0
40
60
80
100
Hodgkin’s Disease – Anatomic Stage
100
0
D
Stage I
80
60
Stage II
All Stages,
All Causes
Stage III
Stage IV
40
20
(Data from Kaplan, 1972)
0
2
4
6
Years
8
10
Survival (%)
Survival (%)
C
20
Months
20
40
60
80
100
Coronary Artery Disease – # of Involved Vessels
100
80
1 Artery
60
2 Arteries
40
3 Arteries
LCA
20
(Data from Proudfit et al, 1978)
0
2
4
6
8
Years
10
Relative Risk of Death Over 12-15 Years in
rheumatoid arthritis (RA) and
cardiovascular (CV) disease according to
baseline severity indicators
RA – 75 pts – 15 yrs – Pincus et al, Ann Int Med 120:26,1994
Functional status on
patient questionnaire
# of Involved Joints
< vs > 91.5% “with ease”
> vs < 18 joints
2.9:1
3.0:1
CV disease – 312,000 pts – 12 yrs –
Neaton et al, Arch Int Med 152:56,1992
Serum cholesterol
Systolic blood pressure
Diastolic blood pressure
Smoking
>245 vs <182 mg/Dl
>142 vs <118 mmHg
>92 vs <76 mmHg
>26 vs 0 cigarettes/day
2.9:1
3.0:1
2.9:1
2.9:1
Data adjusted for age, sex, education, disease duration
5-Year Survival in 206 Patients With RA:
Cohort 2 – 1985–1990
Rheumatoid Factor
MHAQ Score
80
80
Survival (%)
100
Survival (%)
100
60
60
Absent (29)
Present (175)
40
20
20
0
0
0
12
24
36
0.00 (12)
0.01–0.99 (91)
1.00–1.99 (86)
>2.00 (21)
40
48
60
Months After Baseline
Callahan LF et al. Arthritis Care Res. 1997;10:381-394.
0
12
24
36
48
Months After Baseline
60
Multi-Dimensional Health Assessment Questionnaire (R771-NP2)
This questionnaire includes information not available from blood tests, X-rays, or any source other
than you. Please try to answer each question, even if you do not think it is related to you at this time.
Try to complete as much as you can yourself, but if you need help, please ask. There are no right or
FOR OFFICE
wrong answers. Please answer exactly as you think or feel. Thank you.
USE ONLY
MDHAQ
Page 1
1. Please check (√) the ONE best answer for your abilities at this time:
Without
With
With
OVER THE LAST WEEK, were you able to:
ANY
SOME
MUCH
Difficulty
Difficulty
Difficulty
a. Dress yourself, including tying shoelaces and
doing buttons?
_____0
_____1
_____2
b. Get in and out of bed?
_____0
_____1
_____2
c. Lift a full cup or glass to your mouth?
_____0
_____1
_____2
d. Walk outdoors on flat ground?
_____0
_____1
_____2
e. Wash and dry your entire body?
_____0
_____1
_____2
f. Bend down to pick up clothing from the floor?
_____0
_____1
_____2
g. Turn regular faucets on and off?
_____0
_____1
_____2
h. Get in and out of a car, bus, train, or airplane?
_____0
_____1
_____2
i. Walk two miles or three kilometers, if you wish?
_____0
_____1
_____2
j. Participate in recreational activities and sports
_____0
_____1
_____2
as you would like, if you wish?
k. Get a good night’s sleep?
_____0
_____1.1 _____2.2
l. Deal with feelings of anxiety or being nervous?
_____0
_____1.1 _____2.2
m.Deal with feelings of depression or feeling blue?
_____0
_____1.1 _____2.2
UNABLE
To Do
_____3
_____3
_____3
_____3
_____3
_____3
_____3
_____3
_____3
_____3.3
_____3.3
_____3.3
NO                      PAIN AS BAD AS
PAIN 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10 IT COULD BE
3. Please place a check (√) in the appropriate spot to indicate the amount of pain you
are having today in each of the joint areas listed below:
None
Mild Moderate Severe
None
Mild Moderate Severe
i.RIGHT FINGERS
j.RIGHT WRIST
k.RIGHT ELBOW
l.RIGHT SHOULDER
m.RIGHT HIP
n.RIGHT KNEE
o.RIGHT ANKLE
p.RIGHT TOES
q.NECK
r.BACK
2
4. Considering all the ways in which illness and health conditions may affect you at this
time, please indicate below how you are doing:
VERY                     
WELL 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10
For Office Use Only: RAPID 3
Please turn to the other side
RAPID 3 (0-10)
RAPID 4
VERY
POORLY
16=5.3
17=5.7
18=6.0
19=6.3
20=6.7
21=7.0
22=7.3
23=7.7
24=8.0
25=8.3
26=8.7
27=9.0
28=9.3
29=9.7
30=10
2.PN (0-10)
4.PTGL (0-10)
RAPID 3 (0-30)
3.a-pPTJT(0-10)
1=0.2
25=5.2
2=0.4
26=5.4
3=0.6
27=5.6
4=0.8
28=5.8
5=1.0
29=6.0
6=1.3
30=6.3
7=1.5
31=6.4
8=1.7
32=6.7
9=1.9
33=6.9
10=2.1 34=7.1
11=2.3 35=7.3
12=2.5 36=7.5
13=2.7 37=7.7
14=2.9 38=7.9
15=3.1 39=8.1
16=3.3 40=8.3
17=3.5 41=8.5
18=3.8 42=8.8
19=4.0 43=9.0
20=4.2 44=9.2
21=4.4 45=9.4
22=4.6 46=9.6
23=4.8 47=9.8
24=5.0 48=10
?
?
?
?
RAPID 4 (0-40)
RAPID 4 (0-10)
NR: 1=0.3, 2=0.7, 3=1.0 LS: 4=1.3, 5=1.7, 6=2.0
NR: 1=0.3, 2=0.5, 3=0.8, 4=1.0
LS: 5=1.3, 6=1.5, 7=1.8, 8=2.0
MS: 7=2.3, 8=2.7, 9=3.0, 10=3.3, 11=3.7, 12=4.0
MS: 9=2.3, 10=2.5, 11=2.8, 12=3.0, 13=3.3, 14=3.5, 15=3.8, 16=4.0
HS: 13=4.3, 14=4.7, 15=5.0, 16=5.3, 17=5.7,18=6.0,
HS: 17=4.3, 18=4.5, 19=4.8, 20=5.0, 21=5.3, 22=5.5, 23=5.8, 24=6.0,
19=6.3, 20=6.7, 21=7.0, 22=7.3, 23=7.7, 24=8.0,
25=6.3, 26=6.5, 27=6.8, 28=7.0, 29=7.3, 30=7.5, 31=7.8, 32=8.0,
25=8.3, 26=8.7, 27=9.0, 28=9.3, 29=9.7, 30=10.0
33=8.3, 34=8.5, 35=8.7, 36=9.0, 37=9.3, 38=9.5, 39=9.8, 40=10.0
NR: 1=0.2, 2=0.4, 3=0.6, 4=0.8 5=1.0 LS: 6=1.2, 7=1.4, 8=1.6, 9=1.8, 10=2.0,
RAPID 5
MS:11=2.2, 12=2.4, 13=2.6, 14=2.8, 15=3.0, 16=3.2, 17=3.4, 18=3.6, 19=3.8, 20=4.0
(0-10)
HS: 21=4.2, 22=4.4, 23=4.6, 24=4.8, 25=5.0, 26=5.2, 27=5.4, 28=5.6, 29=5.8, 30=6.0, 31=6.2, 32=6.4, 33=6.6, 34=6.8, 35=7.0,
36=7.2, 37=7.4, 38=7.6, 39=7.8, 40=8.0, 41=8.2, 42=8.4, 43=8.6, 44=8.8, 45=9.0, 46=9.2, 47=9.4, 48=9.6, 49=9.8, 50=10.0
Copyright: Health Report Services, Telephone 615-936-2151, E-mail [email protected]
1=0.3
2=0.7
3=1.0
4=1.3
5=1.7
6=2.0
7=2.3
8=2.7
9=3.0
10=3.3
11=3.7
12=4.0
13=4.3
14=4.7
15=5.0
_____3
2. How much pain have you had because of your condition OVER THE PAST WEEK? Please
indicate below how severe your pain has been:
a.LEFT FINGERS
b.LEFT WRIST
c.LEFT ELBOW
d.LEFT SHOULDER
e.LEFT HIP
f.LEFT KNEE
g.LEFT ANKLE
h.LEFT TOES
1.a-j FN (0-10)
\ \\
MDGLOBAL(0-10))
RAPID 5 (0-50)
HAQ and Multidimensional HAQ (MDHAQ)
1st report
Patient completion
No. ADL
Pain VAS
Pt Global VAS
Psych, sleep
RADAI self-report
joint count
Fatigue
Review of systems
Medical history
Demographic data
Social history
Scoring templates
Index
MD scan (“eyeball”)
Time to score
HAQ
MDHAQ
1980
5–10 min
20
10 cm line
10 cm line
No
1999
5–10 min
10
21 circles
21 circles
Sleep, anxiety,
depression
No
No
No
No
No
No
No
No
30 secs
40 secs
Yes
VAS
60 symptoms
Surgery, side effects
Yes
Yes
Yes
RAPID
5 secs
10 secs
HAQ & anti-CCP – 2 measures of RA
1st report
Advance
HAQ
1980
Quantitate
physical
function
Related to
pathogenesis
---Useful in diagnosis
+
% abnormal in RA
>90%
Monitor pt status
++++
Predict work disability ++++
Predict mortality
++++
Cost
appx $10
% of patients measured 20%
anti-CCP
1996
Recognize
RA in RF patients
++++
++
60-70%
+
?
?
appx $100
80%
A Practical System That (Almost) Works
For Routine Assessment of Functional
Status, Fatigue and Psychological
Distress
1. Patient given 2-page questionnaire by
receptionist: completed in waiting room
2. Nurse (or physician) reviews and/or
completes medication data
3. Physician does as little as possible:
completes brief data (may include joint
count)
4. Office staff enters flow sheet with
laboratory data
Considering all the ways in which illness and
health conditions may affect you at this time,
please indicate below how you are doing:
VERY                     
VERY
WELL 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10 POORLY
VERY
WELL
______________________________________________
VERY
POORLY
RADAI Self-Report Joint Count
3. Please place a check (√) in the appropriate spot to indicate the amount of pain you
are having today in each of the joint areas listed below:
None
Mild
Moderate Severe
None
a.LEFT FINGERS
b.LEFT WRIST
c.LEFT ELBOW
d.LEFT SHOULDER
e.LEFT HIP
f.LEFT KNEE
g.LEFT ANKLE
h.LEFT TOES
i.RIGHT FINGERS
j.RIGHT WRIST
k.RIGHT ELBOW
l.RIGHT SHOULDER
m.RIGHT HIP
n.RIGHT KNEE
o.RIGHT ANKLE
p.RIGHT TOES
q.NECK
r.BACK
Stucki G et al. Arthritis Rheum. 1995;38:795-798.
Mild
Moderate Severe
Symptom Checklist From MDHAQ
Please check (√) if you have experienced
any of the following over the last month:
__Fever
Weight gain (>10 lb)
Weight loss (<10 lb)
Feeling sickly
Headaches
Unusual fatigue
Swollen glands
Loss of appetite
Skin rash or hives
Unusual bruising or
bleeding
Other skin problems
Loss of hair
Dry eyes
Other eye problems
Problems with hearing
Ringing in the ears
Stuffy nose
Sores in the mouth
Dry mouth
Problems with smell
or taste
__Lump in your throat
Cough
Shortness of breath
Wheezing
Pain in the chest
Heart pounding (palpitations)
Trouble swallowing
Heartburn or stomach gas
Stomach pain or cramps
Nausea
Vomiting
Constipation
Diarrhea
Dark or bloody stools
Problems with urination
Gynecologic (female) problems
Dizziness
Loss of balance
Muscle pain, aches, or cramps
Muscle weakness
__Paralysis of arms or legs
Numbness or tingling in arms/legs
Fainting spells
Swelling of hands
Swelling of ankles
Swelling in other joints
Joint pain
Back pain
Neck pain
Use of drugs not sold in stores
Smoked cigarettes
More than 2 alcoholic drinks/day
Depression - feeling blue
Anxiety - feeling nervous
Problems with thinking
Problems with memory
Problems with sleeping
Sexual problems
Burning in sex organs
Problems with social activities
Recent Medical History – Self-report
Over the last 6 months have you had [please check (√)]:
No
No
No
No
No
No
No
No
No
No
No
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
An operation
Inpatient hospitalization
A new illness, accident or trauma
An important new symptom
Side effect(s) of any drug
Cigarettes regularly
Change(s) of arthritis drugs or other drugs
Change of address
Change of marital status
Change of job or work duties, quit work, retired
Change of medical insurance, Medicare, etc.
Change of primary care or other doctor
Please explain any “yes" answer below, or indicate any
other health matter that affects you:
___________________________________________________________
RA 61 yo M (#9) Onset: 01/1996 Visit 1
Visit Date
Function (0-3)
Pain (0-10)
Global (0-10)
ESR
Prednisone
Methotrexate
11/4/03
0.8
9.6
8.9
43
N3qd
N10qw
Folic Acid
N1qd
Tylenol w/Codeine
30tid
Naproxen
880q6h
N = new drug, C = change in dose, T = taper, D/C = discontinue
RA 61 yo M (#9) Onset: 01/1996 Visit 2
Visit Date
11/4/03
1/13/04
0.8
9.6
8.9
43
0
0.3
0.3
8
N3qd
1bid
N10qw
C20qw
Folic Acid
N1qd
1qd
Tylenol w/Codeine
30tid
30tid
880q6h
440bid
Function (0-3)
Pain (0-10)
Global (0-10)
ESR
Prednisone
Methotrexate
Naproxen
N = new drug, C = change in dose, T = taper, D/C = discontinue
RA 61 yo M (#9) Onset: 01/1996 Visit 3
Visit Date
11/4/03
1/13/04
4/20/04
0.8
9.6
8.9
43
0
0.3
0.3
8
0.1
0.2
0.3
13
N3qd
1bid
1bid
N10qw
C20qw
20qw
Folic Acid
N1qd
1qd
1qd
Tylenol w/Codeine
30tid
30tid
D/C
880q6h
440bid
440bid
Function (0-3)
Pain (0-10)
Global (0-10)
ESR
Prednisone
Methotrexate
Naproxen
N = new drug, C = change in dose, T = taper, D/C = discontinue
RA 61 yo M (#9) Onset: 01/1996 Visit 4
Visit Date
11/4/03
1/13/04
4/20/04
9/28/04
0.8
9.6
8.9
43
0
0.3
0.3
8
0.1
0.2
0.3
13
0
0.6
N3qd
1bid
1bid
C3bid
N10qw
C20qw
20qw
15qw
Folic Acid
N1qd
1qd
1qd
1 qd
Tylenol w/Codeine
30tid
30tid
D/C
Function (0-3)
Pain (0-10)
Global (0-10)
ESR
Prednisone
Methotrexate
1.0
10
N = new drug, C = change in dose, T = taper, D/C = discontinue
RA 61 yo M (#9) Onset: 01/1996 Visit 5
Visit Date
11/4/03
1/13/04
4/20/04
9/28/04
12/28/04
0.8
9.6
8.9
43
0
0.3
0.3
8
0.1
0.2
0.3
13
0
0.6
1.0
10
0
6.0
5.5
14
N3qd
1bid
1bid
C3bid
3bid
N10qw
C20qw
20qw
15qw
C25qw
Folic Acid
N1qd
1qd
1qd
1 qd
1qd
Tylenol w/Codeine
30tid
30tid
D/C
880q6h
440bid
440bid
440bid
440bid
Function (0-3)
Pain (0-10)
Global (0-10)
ESR
Prednisone
Methotrexate
Naproxen
Adalimumab
N40qow
N = new drug, C = change in dose, T = taper, D/C = discontinue
RA 61 yo M (#9) Onset: 01/1996 Visit 10
Visit Date
11/4/03
1/13/04
4/20/04
9/28/04
12/28/04
12/20/05
0.8
9.6
8.9
43
0
0.3
0.3
8
0.1
0.2
0.3
13
0
0.6
1.0
10
0
6.0
5.5
14
0
1
1
4
N3qd
1bid
1bid
C3bid
3bid
T3bid
N10qw
C20qw
20qw
15qw
C25qw
15qw
Folic Acid
N1qd
1qd
1qd
1 qd
1qd
1qd
Tylenol w/Codeine
30tid
30tid
D/C
880q6h
440bid
440bid
440bid
440bid
Function (0-3)
Pain (0-10)
Global (0-10)
ESR
Prednisone
Methotrexate
Naproxen
Adalimumab
N40qow
N = new drug, C = change in dose, T = taper, D/C = discontinue
40qow
RAPID3 vs DAS in 285 RA Patients
Spearman
correlation
rho = 0.657
RAPID3 vs CDAI in 285 RA Patients
Spearman
Correlation
rho = 0.738
DAS28, CDAI and RAPID Categories
DAS Categories Fransen and van Riel, 2005
<2.6
=
Remission
2.6–3.19
=
Low Activity
3.2–5.1
=
Moderate Activity
>5.1
=
High Activity
CDAI Categories Aletaha and Smolen, 2005
>22
=
High Activity
10.1–22.0
=
Moderate Activity
2.9–10.0
=
Low Activity
<2.8
=
Remission
Proposed RAPID Categories
<1.0
=
Near Remission – therapy is working
1.01–2
=
Low Severity – maybe change therapy
2.01–4.0
=
Moderate Severity – consider strongly
change in therapy
>4.0
=
High Severity – change therapy or have
a good reason not to do so
DAS28 Compared to RAPID3 Scores in
285 Patients at 3 Sites
RAPID 3 Severity
DAS28
Activity
4.1–10=
High
2.1–4.0=
Moderate
1.1–2.0=
Low
0–1.0=Near
Remission
Total
>5.1=
High
37 (74%)
11 (22%)
1 (2%)
1 (2%)
50 (17%)
3.2–5.1=
Moderate
39 (43%)
27 (30%)
16 (18%)
8 (9%)
90 (32%)
2.6–3.19=
Low
4 (10%)
15 (38%)
10 (25%)
11 (27%)
40 (14%)
0–2.6=
Remission
10 (10%)
18 (17%)
24 (23%)
53 (50%)
105 (37%)
Total
90 (31%)
71 (25%)
51 (18%)
73 (26%)
285
CDAI Compared to RAPID3 Scores in
285 Patients at 3 Sites
RAPID 3 Severity
CDAI
Activity
4.1–10=
High
2.1–4.0=
Moderate
1.1–2.0=
Low
0–1.0=Near
remission
Total
>22=
High
39 (78%)
9 (18%)
1 (2%)
1 (2%)
50 (17%)
10.1–22=
Moderate
36 (40%)
33 (36%)
15 (17%)
6 (7%)
90 (32%)
2.9–10=
Low
15 (16%)
28 (30%)
25 (27%)
25 (27%)
93 (33%)
0 (0%)
1 (2%)
10 (19%)
41 (79%)
52 (18%)
90 (31%)
71 (25%)
51 (18%)
73 (26%)
285
0–2.8=
Remission
Total
Changes in RAPID3 Scores Over 5 Years
in RA Patients in Usual Care 1996-2001
Patients in Each RAPID3 Category (%)
100%
RAPID3 categories:
53%
37%
29%
36%
30%
75%
25%
33%
30%
25%
50%
30%
27%
25%
3%
Baseline
(N=60)
12%
28%
17%
13%
0%
18%
18%
21%
13%
6 mo
(N=60)
12 mo
(N=55)
24 mo
(N=56)
60 mo
(N=43)
High severity
(>4)
Moderate severity
(2.01-4)
Low severity
(1.01-2)
Near remission
(1)
Self-report scores of all 60 new RA
patients seen between 1996-2001
6, 12, 24, and 60 months after baseline
6
Mean values
5
Fatigue
Pain
Pt global
Function
RAPID
4
3
2
1
0




Baseline 6 mo 12 mo 24 mo

60 mo
Multidimensional Health Assessment Questionnaire
AT THIS MOMENT, are you able to:
Dress yourself, including tying shoelaces and
doing buttons?
Get in and out of bed?
Lift a full cup or glass to your mouth?
Walk outdoors on flat ground?
Wash and dry your entire body?
Bend down to pick up clothing from the floor?
Turn regular faucets on and off?
Get in and out of a car, bus, train or airplane?
Walk two miles?
Participate in sports and games as you would like?
Get a good night’s sleep?
Deal with feelings of anxiety or being nervous?
Deal with feelings of depression or feeling blue?
Without ANY
Difficulty
With SOME
Difficulty
With MUCH
Difficulty
UNABLE
To Do
----------------------------------------
----------------------------------------
----------------------------------------
----------------------------------------
How much pain have you had because of your condition IN THE PAST WEEK?
Place a mark on the line below to indicate how severe your pain has been:
NO
PAIN
                    
0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10
PAIN AS
BAD AS IT
COULD BE
Considering all the ways in which your illness and and health conditions
may affect you at this time, place a mark to show how you are doing:
VERY
WELL
                    
0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10
VERY
POORLY
RAPID (Routine Assessment of
Patient Index Data) Measures
Index:
RAPID 3
RAPID 4
PTJC
RAPID 4
MDJC
RAPID5
Physical
Function
√
√
√
√
Pain
√
√
√
√
√
√
√
√
Patient Global
Estimate
Patient Joint
Count (RADAI)
MD/Assessor
Joint Count
MD/Assessor
Global Estimate
√
√
√
√
Spearman Correlation Coefficients in
274 Patients with RA – All p<0.001
(#) = Number of identical measures
Measure
CDAI
RAPID3
RAPID4PTJC
RAPID4MDJC
RAPID 5
DASvs
0.84 (3)
0.66 (1)
0.65 (1)
0.73 (3)
0.69 (1)
CDAI vs
--0.74 (1)
0.74 (1)
0.83 (3)
0.80 (2)
All results, P <0.001
DAS vs RAPID in AIM Abatacept Trial
DAS28 RAPID2 RAPID3
RAPID
4-MD
RAPID
4-JC
RAPID5
Mean Change ( % )
0%
-10%
-20%
-30%
-21%
-25%
-28%
-27%
-30%
-32%
Control
Abatacept
-40%
-43%
-47%
-50%
-54%
-60%
-52%
-56%
-61%
-70%
Pincus , Maclean, Hines, Bergman, Yazici,. EULAR. 2007
Some limitations of patient self-report
questionnaires
1. Need for translation – language
issues
2. Cultural and linguistic issues
3. Possibility of “gaming” by patient,
health professional to provide
desired responses
4. Not specific to any disease
Can a Multi-Dimensional Health
Assessment Questionnaire (MDHAQ)
and Routine Assessment of Patient
Index Data (RAPID) scores be
informative in patients with all
rheumatic diseases?
Pincus T, Sokka T.
Best Pract Res Clin Rheumatol. 2007;21:733-753.
The MDHAQ in Clinical Rheumatology
• In rheumatoid arthritis, the MDHAQ
distinguishes MTX or LEF from placebo in a
clinical trial as effectively as a joint count
or the ACR 20
• In osteoarthritis, the MDHAQ distinguishes
NSAID from acetaminophen as effectively
as the WOMAC
• In fibromyalgia, the MDHAQ distinguishes
patients from those with rheumatoid
arthritis as effectively as an ESR
Pain/MHAQ Ratio in RA and Fibromyalgia
P-VAS/D-ADL Ratio
10
9
2 Years
8
>2 Years
7
6
5
4
3
2
1
0
Rheumatoid
Arthritis
Non-Inflammatory Diffuse
Muskuloskeletal Pain
Callahan and Pincus. Arthritis and Rheumatism. 1990;33:1317.
DNA Binding of Serums- SLE and Control Patients
% DNA Bound
100
90
Other = Diseased controls
80
SS = Sjögren’s Syndrome
70
SLE = Unselected Patients
with SLE
60
50
40
30
Value of 20% indicates
abnormal binding activity
20
10
0
Normal (84)Other (57)SS (24) SLE (44)
Pincus et al.
NEJM. 1969;281:701.
SLE 39 yo F — Onset: 09/2004 Education: 12
Visit Date
Function (0-10)
Pain (0-10)
Global (0-10)
RAPID3 (0-30)
RAPID3 (0-10)
ESR
Ibuprofen
Prednisone
Solumedrol
Mycophenolate
mofetil
Hydroxychloroquine
15 Feb 05 17 May 05
4.3
5.6
6.5
16.4
5.5
66
0
2
6
8
2.7
36
19 Jul 05
20 Sep 05 23 May 06 26 Sep 06
0
4
3
7
2.3
—
0
3.5
2
5.5
1.8
8
0
0.4
0.1
0.5
0.2
11
0
0.5
0.5
1
0.3
15
T-5 qd
5 qd
C-4 qd
4 qd
0-600 tid 600 tid
N-5 qd
C-10 qd
N-80
N-500 bid 1000 bid 1000 bid 1000 bid 1000 bid
N-200 bid D-200 bid
N=new drug; C=change in dose; T=taper; D/C=discontinue.
Quantitative Monitoring of a
Patient With SLE over 180 days:
ESR, anti-DNA, CH50
Creat
Clear
(mL/min)
LE
Prep
CH50
100
140
50
90
0
40
-
+ +
-
-
-
-
200
100
% DNA
50 Bound
100
0
Prednisone
(mg/d)
ESR
(mm/hr)
0
50
0
20
40
60
80
100 120
Pincus T et al. New Engl J Med. 1969;281:701-705.
140
160
180 Days
Is it Better to Have 80% of the
Information in 100% of Patients
or 100% of the Information in
5% of Patients?
Pincus T, Wolfe F.
J Rheumatol. 2005;32:575-577.
Activities of Daily Living (ADL)
in Prognosis of Nonrheumatic Diseases
• In congestive heart failure, ADL predicts
36-mo mortality as ejection fraction
(Konstam. Am J Cardiol. 1996;78:890)
• In AIDS, ADL predict 36-month mortality as
CD4/CD8 ratios, clinical AIDS prognostic
staging (CAPS), severity classification for
AIDS hospitalizations (SCAH)
(Justice. J Clin Epidemiol. 1996;49:193)
• In hospitalized elderly patients, ADL predict
one-year mortality beyond physiologic data
and comorbidities
(Covinsky. J Gen Intern Med. 1997;12:203)








Requirements for clinic-based
measurement tool
Valid
Reliable
Feasible – easily completed by patient
Clinically useful – amenable to simple
review by MD prior to seeing patient
Acceptable to MD and patient
Amenable to charting on flow sheet
Saves time for patient and health
professional to focus on major concerns of
the patient
Recognize underappreciated disease
severity and
patient concerns
Patient Questionnaires in
Clinical Research vs Clinical Care
Clinical research
Selected patients
Long, many pages
Takes time for pt, staff
Complex scoring
No scoring at visit
Results unknown at visit
Send to data center
Enter into computer
Research agenda
Clinical care
All patients
1-page patient friendly,<10 min
Saves time for MD
“Eyeball” results
Scoring templates for MD
Adds to clinical care
Review with patient
Enter onto flowsheet
document, improve care
Quality improvement agenda
Prediction of premature
mortality according to blood
pressure and cholesterol
converted hypertension and
hypercholesterolemia from
optional treatments to major
public health campaigns.
Imagine doctors saying that they
do not measure blood pressure
or cholesterol because
“it takes too much time” or
“the staff will not cooperate,”
as suggested for why they do not
measure physical function.
Should Contemporary
Rheumatology Clinical Trials Be
More Like Standard Patient Care
and Vice Versa?
Pincus T, Sokka T.
Ann Rheum Dis.
2004;63(Suppl II):ii32-ii39.
Should rheumatology
health professionals keep
track of their patients with
Gestalt impressions or
with quantitative data?