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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]. What is the most significant risk factor for mortality over 5-20 years in patients with RA?. 5. - PowerPoint PPT Presentation
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A proposed 15 second checklist of 10 measures for all usual care rheumatology
visits
Theodore Pincus, MDClinical Professor of Medicine
New York University school of [email protected]
1
What is the most significant risk factor for mortality over 5-20 years in patients
with RA?
2
1 2 3 4 5
0% 0% 0%0%0%
51. Presence of
rheumatoid factor
2. Poor functional status
3. Quantitative radiographic score
4. Presence of ACRA (anti-CCP)
5. Number of swollen joints
What is the number of units in a Sharp/van der Heidje radiographic
score?
3
64128
224448
660
0% 0% 0%0%0%
51. 64
2. 128
3. 224
4. 448
5. 660
Approximately what proportion of new patients with RA have an ESR greater than
28mm/Hr?
4
50%60%
70%80%
90%
0% 0% 0%0%0%
51. 50%
2. 60%
3. 70%
4. 80%
5. 90%
Approximately what proportion of new patients with rheumatoid arthritis have anti-citrullinated peptide
antibodies (ACPA or anti-CCP)?
5
50%60%
70%80%
90%
0% 0% 0%0%0%
51. 50%
2. 60%
3. 70%
4. 80%
5. 90%
What is the primary reason that “revolutionary” new biological therapies for RA lead to only 60% ACR 20 responses?
Non-ta
rgeted d...
Fibro
myalgi
a
Damage to jo
in...
Design of c
lin...
25% 25%25%25%5
1. Non-targeted different cytokines causing inflammation
2. Fibromyalgia
3. Damage to joints
4. Design of clinical trails
A proposed 15 second checklist of 10 measures for all usual care rheumatology
visits
Theodore Pincus, MDClinical Professor of Medicine
New York University school of [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?
13%
32%
11%
14%
16%
14%
Never
1%–24% of visits
25%–49% of visits
50%–74% of visits
75%–99% of visits
Always
For patients with RA under your care (not including patients in clinical trials), how often do you perform
formal tender and swollen joint counts?
Question for Rheumatologists
Pincus T, et al. Ann Rheum Dis. 2006;65:820-822.
Clinical Decisions SurveyAll 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 0-20%, 21-40%, 41-60%, 61-80%, or 81-100% of information for diagnosis and management of 8 diseases:
1.hypertension2.diabetes mellitus3.rheumatoid arthritis 4.hypercholesterolemia 5.pulmonary fibrosis6.ulcerative colitis7.lymphoma8.congestive heart failure
Highest ranked source of clinical information 588 MDs:
ElementCongHeartFail-ure
Dia-betes Mell-litus
Hyp-erten-
sion
Hyp-erli-pid-
emia
Lym-pho-ma
Pul-mo-naryFib
Rheu-mat
Arth-ritis
Ulcer-ativeColi-tis
Vital Signs
Patient History
Physical Exam
Lab tests
Other studies
McCollum, Durusu Tanriover, Akalžn , H Yazici, Pincus: EULAR 2010
>50%: 20-50%: <20%:
•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.
Disease Standard BiomarkerMeasure
Biomarker Measure in clinical
trials
BiomarkerMeasure in
clinical care
Hyper-tension
Blood pressure
Blood pressure
Blood pressure
Diabetes Glucose,
Hgb A1c
Glucose,
Hgb A1c
Glucose,
Hgb A1c
Rheuma-toid
Arthritis
RF, anti-CCP, ESR, CRP
ACR Core Data Set, DAS28
Standard scientific measures in medical care
Standard scientific measures in medical care
Disease Standard BiomarkerMeasure
Biomarker Measure in
clinical trials
BiomarkerMeasure in
clinical care
Hyper-tension
Blood pressure
Blood pressure
Blood pressure
Diabetes Glucose,
Hgb A1c
Glucose,
Hgb A1c
Glucose,
Hgb A1c
Rheuma-toid
Arthritis
RF, anti-CCP, ESR, CRP
ACR Core Data Set, DAS28
RF, anti-CCP, ESR, CRP
Standard scientific measures in medical care
Standard scientific measures in medical care
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 measuresSource: MD
examX-ray
Lab Patient self-report
Tender joint count √√
Swollen joint count √√
Assessor Global estimate √√
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?
"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
Textbook statements concerning ESR in RA
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-roundsuntan and brilliant oratory may overcome absence of any supporting data
ELEGANCE BASED MEDICINE - where the sartorialsplendor 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
ESR Values in Patients With RA Wolfe F, Michaud K, J
Rheumatol. 1994;21:1227–1237. Wichita KS, USA
ESR ≥ 28 mm/h
ESR < 28 mm/h
Females 63% 37%
Males 55% 45%
Similar results have been reported from:Nashville, TN, USA Jyvaskyla, FinlandOslo, Norway Nancy, FranceGroningen, The Netherlands Belfast, Ireland
Location Yr of
reportn
% ESR<28 mm/Hr
Mean Median
ESR (mm/h)
Wichita, KS, USA1 1994 1556 F37%,M45% 37F, 34M
Oslo, Norway2 1996 237 26
Nancy, France2 1996 135 29
Groningen, Netherlands2 1996 283 28
Belfast, N Ireland2 1996 51 28
Jyvaskyla, Finland 3 2009 1892 45% 30
Nashville, TN, USA3 2009 738 47% 30
ESR in 7 Locations 1994-2005
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)
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
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 - 57%
• CRP >10 - 58%
• Rheumatoid factor positive - 69%
• Anti-CCP positive - 67%
• Function score >2/10 - 70%
• Pain score >2/10 - 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 Years1950s Rheumatoid factor1960s Immune complexes1970s HLA type, Prostaglandins1980s Shared epitope 1990s Monoclonal Abs,Anti-CCP2000s Genes, cytokine targets
•Of course, the laboratory remainsthe primary source of further understanding of pathogenesisand 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-eight-joint 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 trials2.72 2.65
2.06
1.66
1.30
0.22
0.94
2.12
1.48 1.43
1.001.001.001.00
1.12
1.421.55
1.10
0.60
1.86
1.27
1.601.52
1.17
1.48
0.92
1.36
2.14
0.00
0.50
1.00
1.50
2.00
2.50
3.00
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
Effect Size
Patient questionnaire
–1.5 –1.3 – 1.1 – 0.9 – 0.7 – 0.5 – 0.3 – 0.1 0.1 0.3 0.5
Malalignment
Limited motionJoint space narrowing
TendernessSwelling
Pain on motion
Radiographic
Type of measure:
Joint count
Laboratory
Clinical
Deformity
Erosions
Erythrocyte sedimentation rateRheumatoid factor titer
HemoglobinMorning stiffness
Grip strengthWalk time
Button timeFunctional status–MHAQ
Global statusPain–visual analog scale
Helplessness
Better
Worse
MHAQ=modified Health Assessment Questionnaire.
Callahan, Pincus et al. Arthritis Care Res 1997;10:381–94
Changes in measures in 100 RA patients – 1985-1990 over 5 years - effect size
Some Limitations of Formal Swollen and Tender Joint
Counts • Relative efficiencies to distinguish 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
TEMPO Trial: Year 2 Radiograph: Change in Total Sharp Score from
Baseline to Year 2
* p < 0.05, E vs MTX† p < 0.05, Combination vs MTX ‡ p < 0.05, Combination vs E
-1
0
1
2
3
4
5
6
7
8
Ch
ang
e fr
om
bas
elin
e (M
ean
+/-
SE
)
MTX = 206
E = 203
MTX+E = 2133.34
(CI 1.18, 5.50)
1.10* (CI 0.13, 2.07)
-0.56†‡ (CI –1.05, -0.06)
1 1.59 -0.54 0.52 2.8 0.4 3.7 1.3 3 5.70
50
100
150
200
250
300
350
400
450
ERA ETA ERA MTX TEMPOCombi
TEMPO ETA TEMPO MTX IFX Combi IFX MTX PREMIERCombi
PREMIERADA
PREMIERMTX
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
RR (95% CL)
P Value
Age 1.07 <0.001 1.06 <0.001
RA Cohort #2- Cox Proportional Hazards Model Analyses Including Demographic, Functional, Self-Report, Joint Count, X-ray, Laboratory and Disease
Variables in 206 patients 1985-1990
P Value
Comorbidity 1.63 <0.001 1.40 0.02
MHAQ ADL Score 2.00 0.003 1.76 0.02
Disease duration 1.04 0.02 -- --
Education 0.89 0.007 -- --
ESR 1.01 0.005 -- --
Joint count 1.02 0.10 -- --
Walking time 1.03 0.04 -- --
X-ray
Univariate Stepwise Model
Callahan, Brooks, Pincus, Arthritis Care Res 10:381,1997
1.40 0.17 -- --
RR (95% CL)
0%
25%
50%
75%
100%
Physicalfunction(N=18)
Handradio-graph(N=18)
Jointcount (N=18)
Rheum-atoidfactor(N=29)
ESR(N=19)
Extra-articulardisease(N=18)
Co-morbidities
(N=23)
Socio-economic
status(N=13)
22%
11%
28%
39%
50%
50%
37%
32%
32%
72%
6%
22%
65%
4%
30%
46%
31%
23%
45%
34%
21%
44%
17%
39%
Significant in multivariate analyses Significant in univariate analyses Not Significant
Significance of 8 variables as predictors of mortality in 53 RA cohorts
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
Radiographs ESR, CRP
Shared epitope
Rheumatoid factorJoint deformity
Duration of disease
Functional disabilityPainPatient global
Joint tendernessFatigueAge
Strongly and Weakly Related Measures to Assess RA
Joint swelling
MRI Can Better Identify Early Bone Erosions than X-ray
Methotrexate in RA Care: 1980-2005Jyvaskyla, 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 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
Patient self-report questionnaires in usual rheumatology care
Multi-Dimensional
Health Assessment Questionnai
re (MDHAQ) Page 1
MDHAQ/RAPID3:04 Nov 20033 RA Core Data Set scoresFN (0–10) = 2.7 PN (0–10) = 9.5PTGL (0–10) = 9.0
RAPID3 (0–30) = 21.2
Severity:12.1-30 = High6.1-12 = Moderate3.1-6 = Low0-3 = Near remission
2.7
9.5
9.0
21.2
Indices to assess patients with RAACR 1 DAS28 2 CDAI 3 RAPID3 4
# Tender joints √ 0.56 sq rt (TJC28) 0-28 --
# Swollen joints √ 0.28sq rt (SJC28) 0-28 --
MD global √ -- 0-10 --ESR or CRP √ 0.70
ln (ESR) -- --Patient function √ -- -- 0-10Patient pain √ -- -- 0-10Patient global √ 0.014
PTGL 0-10 0-10TOTAL 0-10 0-76 0-301. 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 date 4Nov03
Q-Function (0–10) 2.7
Q-Pain (0–10) 9.5
Q-Global (0–10) 9.0
RAPID3 (0–30) 21.2
L-ESR 43
Prednisone N-3qd
T-Methotrexate N10qw
T-Folic acid N1qd
T-Tylenol w/Codeine 30tid
T-Naproxen 880q6h
N=new medication, C=change in dose, T=taper, D/C=discontinue
Visit 1: 14 Nov 2003
RAPID3 versus DAS28 and CDAI in 285 RA patients
Spearman correlation
rho = 0.657Pincus T, et al. J Rheumatol. 2008; 35: 2136-2147.
Spearman correlation
rho = 0.738
DAS28 CDAI
Time to Score RA Measures - Seconds
94
42
106
9.6 4.6
114
0
50
100
150
28 JointCount
HAQ-DI DAS28 CDAI RAPID3(0-10)
RAPID3(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 20033 RA Core Data Set scoresFN (0–10) = 2.7 PN (0–10) = 9.5PTGL (0–10) = 9.0
RAPID3 (0–30) = 21.2
Severity:12.1-30 = High6.1-12 = Moderate3.1-6 = Low0-3 = Near remission
2.7
9.5
9.0
21.2
MDHAQ/RAPID3:13 Jan 20043 RA Core Data Set scoresFN (0–10) = 0 PN (0–10) = 0.5PTGL (0–10) = 0.5
RAPID3 (0–30) = 1.0
Severity:12.1-30 = High6.1-12 = Moderate3.1-6 = Low0-3 = Near remission
0
0.5
0.5
1.0
Visit 2: 13 Jan 2004
N = new drug, C = change in dose, T = taper, D/C = discontinue
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
CDAI (0-76) 43.0 4.5
L-ESR 43 8
T-Prednisone N3qd 3qd
T-Methotrexate N10qw C20qw
T-Folic acid N1qd 1qd
T-Tylenol w/Codeine 30tid 30tid
T-Naproxen 880q6h 440bid
T-Adalimumab
Visit 4 - 28 Sep 2004
N = new drug, C = change in dose, T = taper, D/C = discontinue
Visit Date 4Nov03 13Jan04 20Apr04 28Sep04
Q-Function (0–10) 2.7 0 0.3 0
Q-Pain (0–10) 9.6 0.3 0.2 0.6
Q-Global (0–10) 8.9 0.3 0.3 1.0
RAPID3 (0–30) 21.2 0.6 0.8 1.6
L-ESR 43 8 13 10
T-Prednisone N3qd 3qd 3qd 3qd
T-Methotrexate N10qw C20qw 20qw 15qw
T-Folic acid N1qd 1qd 1qd 1qd
T-Tylenol w/Codeine 30tid 30tid D/C
T-Naproxen 880q6h 440bid 440bid 440bid
0
6.0
5.5
11.5
MDHAQ/RAPID3:28 Dec 20043 RA Core Data Set scoresFN (0–10) = 0 PN (0–10) = 6.0PTGL (0–10) = 5.5
RAPID3 (0–30) = 11.5
Severity:12.1-30 = High6.1-12 = Moderate3.1-6 = Low0-3 = Near remission
0
6.0
5.5
11.5
MDHAQ/RAPID3:28 Dec 20043 RA Core Data Set scoresFN (0–10) = 0 PN (0–10) = 6.0PTGL (0–10) = 5.5
RAPID3 (0–30) = 11.5
Severity:12.1-30 = High6.1-12 = Moderate3.1-6 = Low0-3 = Near remission
Visit 5: 28 Dec 2004
N=new drug, C=change in dose, T=taper, D/C=discontinue
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
CDAI (0-76) 43.0 4.5 1.0 1.5 30.0
L-ESR 43 8 13 10 14
T-Prednisone N3qd 3qd 3qd 3qd 3qd
T-Methotrexate N10qw C20qw 20qw 15qw C25qw
T-Folic acid N1qd 1qd 1qd 1qd 1qd
T-Tylenol w/Codeine 30tid 30tid D/C
T-Naproxen 880q6h 440bid 440bid 440bid 440bid
T-Adalimumab N40qow
0
0
0.5
0.5
MDHAQ/RAPID3:8 Feb 20053 RA Core Data Set scoresFN (0–10) = 0 PN (0–10) = 0.0PTGL (0–10) = 0.5
RAPID3 (0–30) = 0.5
Severity:12.1-30 = High6.1-12 = Moderate3.1-6 = Low0-3 = Near remission
Visit 6: 8 Feb 2005Visit date 4No03 13Ja04 20Ap04 28Se04 28De04 8Fe05
Q-Function (0–10) 2.7 0 0.3 0 0 0Q-Pain (0–10) 9.5 0.5 0.0 0.5 6.0 0.0Q-Global (0–10) 9.0 0.5 0.5 1.0 5.5 0.5RAPID3 (0–30) 21.2 1.0 0.8 1.5 11.5 0.5
L-ESR 43 8 13 10 14 14T-Prednisone N3qd 3qd 3qd 3qd 3qd 3qd
T-Methotrexate N10qw C20qw 20qw 15qw C25qw C15qw
T-Folic acid N1qd 1qd 1qd 1qd 1qd 1qd
T-Tylenol w/Codeine 30tid 30tid D/C
T-Naproxen 880q6h 440bid 440bid 440bid 440bid D/C
T-Adalimumab N40qow 40qow
N=new drug, C=change in dose, T=taper, D/C=discontinue
20001985
0 5 10 15
Disease Duration (Years)
2.0
1.5
1.0
0.5
0.0
MH
AQ
Disease Duration (Years)
MH
AQ
2.0
1.5
1.0
0.5
0.020 0 5 10 15 20
Cross-Sectional Data in Patients With RA – Cohort #2 in 1985 and Cohort #4 in 2000:
Pincus, Sokka, Kautiainen, Arthritis Rheum 52:1009, 2005
Multidimensional Health Assessment Questionnaire (MDHAQ) scores
20001985
0 5 10 15
Disease Duration (Years)
20
16
12
8
4
0
Sw
oll
en J
oin
t C
ou
nt
28
Disease Duration (Years)
Sw
oll
en J
oin
t C
ou
nt
28
20 0 5 10 15 20
20
16
12
8
4
0
Cross-Sectional Data in Patients With RA – Cohort #2 in 1985 and Cohort #4 in 2000:
Swollen Joint Count Scores
Pincus, Sokka, Kautiainen, Arthritis Rheum 52:1009, 2005
Cross-Sectional Data in RA Patients –
Cohort #2 in 1985 and Cohort #4 in 2000: Larsen X-Ray score,% of
Maximum
0
5
10
15
20
25
30
0 5 10 15
Disease duration
La
rso
n s
co
re f
or
ha
nd
s, %
of
ma
x
RF+
RF-
0
5
10
15
20
25
30
0 5 10 15
Disease duration
La
rso
n s
co
re f
or
ha
nd
s, %
of
ma
x
RF+
RF-
1985 2000
Pincus, Sokka, Kautiainen, Arthritis Rheum 52:1009, 2005
Pincus T, Swearingen CJ. [Abstract #1627] Arthritis Rheum 2009;60(Suppl):S608. Presented at ACR, 2009.
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 MTXB. 30 incomplete responders initiating biologic agent
63 Adequate Responders (“Controls”)
30 Incomplete Responders
MTX StartFollow-up
(NO Biologic) MTX StartBiologic
Start
ESR 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
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 Rheum Dis 1999; Sokka et al Ann Rheum Dis 2004)
9-10 Year Survival According to Quantitative Markers in Three Chronic Diseases
Hodgkin’s Disease -Hodgkin’s Disease -Anatomic StageAnatomic Stage
Years
2020
4040
6060
8080
100100
00 22 44 66 88
Su
rviv
al (
%)
Su
rviv
al (
%)
1010
CC
Stage IStage I
Stage IIStage IIAll Stages, All Stages, All CausesAll Causes
Stage IIIStage IIIStage IVStage IV
(Data from Kaplan, 1972)(Data from Kaplan, 1972)
Formal Education LevelFormal Education Level
2020
4040
6060
8080
100100
00 2020 4040 6060 8080 100100 Months
8 Years8 Years
9–12 Years9–12 Years
>12 Years>12 YearsBB
Su
rviv
al (
%)
Su
rviv
al (
%)
(Data from Pincus et al, 1987)(Data from Pincus et al, 1987)
DD Coronary Artery Disease -Coronary Artery Disease - # of Involved Vessels# of Involved Vessels
Years
1 Artery1 Artery
2 Arteries2 Arteries
3 Arteries3 ArteriesLCALCA2020
4040
6060
8080
100100
00 22 44 66 88 1010
Su
rviv
al (
%)
Su
rviv
al (
%)
(Data from Proudfit et al, 1978)(Data from Proudfit et al, 1978)
Activities of Daily LivingActivities of Daily LivingAA100
80
60
40
20
0 20 40 60 80 100
>90%81–90%
71–80%
70%
Su
rviv
al
(%)
Months
(Data from Pincus et al, 1987)(Data from Pincus et al, 1987)
% Active “With Ease”% Active “With Ease”
Rheumatoid Arthritis -Rheumatoid Arthritis - Rheumatoid Arthritis -Rheumatoid Arthritis -
5-Year Survival in 206 Patients With RA: Cohort #2 –
1985-1990
100100
8080
6060
4040
2020
0000 1212 2424 3636 4848 6060
Su
rviv
al (
%)
Su
rviv
al (
%)
Months After BaselineMonths After Baseline
Rheumatoid FactorRheumatoid Factor
Absent (29)Absent (29)
Present Present (175)(175)
100100
8080
6060
4040
2020
0000 1212 2424 3636 4848 6060
Su
rviv
al (
%)
Su
rviv
al (
%)
Months After BaselineMonths After Baseline
MHAQ ScoreMHAQ Score
0.00 (12)0.00 (12)0.01–0.99 (91)0.01–0.99 (91)1.00–1.99 (86)1.00–1.99 (86)>2.00 (21)>2.00 (21)
Callahan LF et al. Arthritis Care Res 10:381,1997
0%
25%
50%
75%
100%
Physicalfunction(N=18)
Handradio-graph(N=18)
Jointcount (N=18)
Rheum-atoidfactor(N=29)
ESR(N=19)
Extra-articulardisease(N=18)
Co-morbidities
(N=23)
Socio-economic
status(N=13)
22%
11%
28%
39%
50%
50%
37%
32%
32%
72%
6%
22%
65%
4%
30%
46%
31%
23%
45%
34%
21%
44%
17%
39%
Significant in multivariate analyses Significant in univariate analyses Not Significant
Significance of 8 variables as predictors of mortality in 53 RA cohorts
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 trials2.72 2.65
2.06
1.66
1.30
0.22
0.94
2.12
1.48 1.43
1.001.001.001.00
1.12
1.421.55
1.10
0.60
1.86
1.27
1.601.52
1.17
1.48
0.92
1.36
2.14
0.00
0.50
1.00
1.50
2.00
2.50
3.00
ARMADA DE011 DE019 STAR
Tender Joint Count
Swollen Joint Count
Assessor Global
CRP
Function (HAQ)
Pain
Patient Global
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
A proposed checklist of 10 measures for patients with rheumatic disease at all visits
MDHAQ:Page 1 of 2
1.a - j: Physicalfunctionk, l, m:
Psychological distress
2.Pain3.RADAI
Self-reportjoint count
4. Patient globalestimate
RAPID3
MDHAQ:Page 25. Review of
systems6. Morning
stiffness 7. Change in
status 8. Exercise 9. Fatigue10.Recent
medical history
11.Demogra-phic data
MD review
Review of Symptoms (ROS)
RA(n=174)
OA(n=32)
FM(n=196)
SLE(n=34)
Spondy(n=30)
Gout(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
Symptoms [0-60] 14.1 9.4 20.5 16.1 11.4 7.7
Quantitative patient MDHAQ scores in new rheumatology patients by diagnosis
FM = fibromyalgia; Spondy = spondylarthropathy. Shaded: Patient measures: FN>3, PN5, PTGL5, FT5, RAPID3>12, SX>20.
RA(n=174)
OA(n=32)
FM(n=196)
SLE(n=34)
Spondy(n=30)
Gout(n=12)
Age (years) 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
% 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
Quantitative demographic and laboratory datain new rheumatology patients by diagnosis
FM = fibromyalgia; Spondy = spondylarthropathy. Shaded: ESR >20, CRP >10.
Highest ranked source of clinical information 588 MDs:
ElementCongHeartFail-ure
Dia-betes Mell-litus
Hyp-erten-
sion
Hyp-erli-pid-
emia
Lym-pho-ma
Pul-mo-naryFib
Rheu-mat
Arth-ritis
Ulcer-ativeColi-tis
Vital Signs
Patient History
Physical Exam
Lab tests
Other studies
McCollum, Durusu Tanriover, Akalžn , H Yazici, Pincus: EULAR 2010
>50%: 20-50%: <20%:
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
A proposed checklist of 10 measures for patients with rheumatic disease at all visits
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?
• 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 physical examination data in RA
RA(n=174)
OA(n=32)
FM(n=196)
SLE(n=34)
Spondy(n=30)
Gout(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
Quantitative physician global estimates in new patients by diagnosis – T Pincus
FM = fibromyalgiaSpondy = spondylarthropathy Shaded: All DOC measures 5
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
Quantitative physician global estimates in new patients by diagnosis – M Bergman
FM = fibromyalgiaSpondy = spondyloarthropathyShaded = highest-scored scale for each diagnostic category
RA(n=174)
OA(n=32)
FM(n=196)
SLE(n=34)
Spondy(n=30)
Gout(n=12)
Patient MDHAQ self-report questionnaire measures for proposed checklist
Function [0-10] 3.2 2.3 3.0 1.9 3.0 1.8Pain [0-10] 5.4 4.4 6.5 3.7 5.9 5.8PT Global [0-10] 5.4 4.4 6.1 4.3 5.1 3.8RAPID3 [0-30] 13.7 10.0 15.4 8.5 13.4 10.2Fatigue [0-10] 5.7 4.2 7.3 5.4 4.5 4.1Symptoms [0-60] 14.1 9.4 20.5 16.1 11.4 7.7Physician global measures for proposed checklist
DOC Global [0-10] 6.3 6.3 6.3 5.0 6.3 5.0Inflammation [0-10] 7.0 3.3 2.3 3.6 7.7 6.0Damage [0-10] 5.0 6.0 1.7 2.3 4.3 3.0Non-inflam/non-damage [0-10] 4.0 3.7 9.0 6.3 4.0 2.3
Quantitative patient MDHAQ scores and physician global estimates in new rheumatology patients by diagnosis
FM = fibromyalgia; Spondy = spondylarthropathy. Shaded: Patient measures: FN>3, PN5, PTGL5, FT5, RAPID3>12, SX>20. All DOC measures 5.
Scientific method in medical care: standardized measurement is
prerequisite
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?