Why is quantitative standardized measurement advantageous in usual clinical care?

Patient questionnaire responses: a standardized, quantitative, “scientific” patient history to

recognize effective and incomplete responses to prednisone,

methotrexate and biological agents

Theodore Pincus, MDClinical Professor of Medicine

New York University School of Medicinetedpincus@gmail.com

Why is quantitative standardized measurement

advantageous in usual clinical care?

Quantitative measurement vs descriptive impressions

“It’s cold outside” – 35ºF or 10ºF?“My child has a fever” – 100ºF or 108ºF?“This wine is expensive”– $60 or $6000?

“The RA patient is better” – –DAS28 ↓ 4.2 or 2.4?–CDAI ↓ 16 or 5? –RAPID3 ↓ 10 or 4?

“Patients with rheumatoid arthritis usually respond to a conservative program of nonsteroidal anti-inflammatory drugs, rest, and physical therapy…”

Prevailing view of rheumatoid arthritis – 1984

Arthritis Rheum 1984;27:1344–1352.

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 trialsIsaacs and Fitzgerald, BMJ 319:1618, 1999,per G. Eknoyan, Baylor Coll Med

Clinicians may all too easily spend years writing “doing well” in the notes of a patient who has become progressively crippled before their eyes…

–Verna Wright

Smith T, et al. Br Med J 1983;287:569.

More accurate information in 1983?

Severe functional declines, work disability, and increased

mortality 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

Rheumatoid Arthritis over 9 years – changes in functional status in activities of daily living and morning stiffness 1973-1982

Pincus et al. Arthritis Rheum. 1984;27:864; J Rheumatol. 1992;19:1051

1973 1982

Morning Stiffness

1973 1982

Activities of daily living

Minutes% No Difficulty

Survival in rheumatoid arthritis 1973-1982

Pincus et al. Arthritis Rheum. 1984;27:864.

RA U.S. 1977 U.S. 2005

No. of reports (cohorts) 50 (54) -- --Total no. of patients 91,618 -- --Total no. of deaths 33,250 -- --Cardiovascular 39.6% 41.0% 38.3%Cancer 16.8% 20.4% 22.8%Renal 5.8% 1.1% 1.8%Respiratory 9.0% 3.9% 5.3%Infection 14.3% 1.0% 4.4%Gastrointestinal 5.1% 2.4% 1.1%Accidents or intoxication 4.2% 5.4% 6.9%RA/musculoskel diseases 9.4% -- --Other 16.0% 24.8% 21.4%

Causes of death: RA patients in 50 published reports 1953–2008, vs U.S. general population

Sokka T, Abelson B, Pincus T. Clin Exp Rheumatol 26(suppl):S35-61, 2008

Survival of Patients With Rheumatoid Arthritis Versus Expected Survival in 10 Locales

Cobb et al, 1953Massachusetts

200400600800

0 10 20 30

Expected for population

Patients with RA

Uddin et al, 1970Ontario

Expected for menWomen with RAMen with RA

0 2 4 6 8 10

Expected for women

Monson and Hall, 1976Massachusetts

(%)5 10 15 20

Women with OAMen with OA

Women with RAMen with RA

Allebeck et al, 1981Sweden

406080

Expected for womenExpected for menWomen with RAMen with RA

Rasker and Cosh, 1981England

Patients with “definite” RAPatients with “classic” RA

4 12 20248 16

Vandenbroucke et al, 1984Netherlands

406080

Expected for womenWomen with RAMen with RA

5 10 15 20 25

Expected for men

Mutru et al, 1985Finland

Expected for womenExpected for men

2 4 6 8 10

Women with RAMen with RA

Mitchell et al, 1986Saskatchewan

406080

Expected for womenExpected for menWomen with RAMen with RA20

5 1510

Vollertsen et al, 1986Minnesota

0.200.400.600.801.00

Expected forpopulationPatients with “classic” RA

04 8 12 1620

Pincus et al, 1987Tennessee

406080

Expected for womenExpected for menWomen with RAMen with RA

9- to 10-Year Survival According to Quantitative Markers in Three Chronic Diseases

Hodgkin’s Disease – Anatomic Stage

0 2 4 6 8

Stage I

Stage IIAll Stages, All Causes

Stage III

Stage IV

(Data from Kaplan, 1972)

0 20 40 60 80 100Months

8 Years

9–12 Years

>12 Years

(Data from Pincus et al, 1987)

D Coronary Artery Disease – # of Involved Vessels

1 Artery

2 Arteries

3 ArteriesLCA20

0 2 4 6 8 10

(Data from Proudfit et al, 1978)

0 20 40 60 80 100

81%–90%

71%–80%

Months(Data from Pincus et al, 1987)

% Active “With Ease”

Rheumatoid Arthritis – Activities of Daily Living Rheumatoid Arthritis – Formal Education Level

Why are quantitative patient history data

needed for clinical care of patients with rheumatoid

arthritis?

Treat-to-target in hypetension or diabetes

“Treat-to-target” in hypertension and diabetes is based on single “gold standard” measure applicable to all patients

Patient history and physical exam are largely irrelevant to “treat-to-target”

Differences: hypertension, diabetes, hyperlipidemia vs

rheumatoid arthritis

Differences: hypertension, diabetes, hyperlipidemia vs

rheumatoid arthritis

Disease Biomarker Positive in1. Hypertension Blood pressure 100%

2. Diabetes mellitus Hgb A1c, glucose 100%

3. Hyperlipidemia Cholesterol, lipids 100%

4. Rheumatoid ESR, CRP, ACPA, arthritis rheumatoid factor 60-70%

Complexities in diagnosis and assessment of patients with rheumatic diseases

No single ‘gold standard’ (e.g., blood pressure, cholesterol) for clinical trials or standard care

Laboratory tests limited in both diagnosis and treatment; primary criteria are clinical

Patient history and physical examination generally are more important in clinical decisions than lab tests

Therefore, indices of 3-7 measures to assess RA quantitatively – include history (pt questionnaire), physical exam, lab tests

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.

Measures in clinical trials and usual care

DiseaseBiomarkerMeasures

Measures in clinical

trials

Measures in usual

Hyper-tension

Blood pressure

Diabetes Glucose,HbA1c

Glucose,HbA1c

Rheumatoid arthritis

RF, ACPA, ESR, CRP

Core Data Set, DAS28,

CDAI, RAPID3

RF, ACPA, ESR, CRP

Clinical Decisions SurveyPlease indicate your opinion of the importance of each of 5 sources: 1) vital signs, 2) patient history, 3) physical examination, 4) laboratory tests, 5) ancillary studies, to provide 0-20%, 21-40%, 41-60%, 61-80%, or 81-100% of information for diagnosis and management of:

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:

Source

CongHeart

Failure

Dia-betes

MellitusHyper-tension

Hyper-lipid-emia

Lymph-oma

Pulmo-nary

Fibrosis RA

Ulcer-ative

Colitis

Vital Signs

Patient History

69% 50%

Physical Exam

64% 68%

Lab tests

96% 98%

Ancillary studies

52% 73% 81% 80%

McCollum, Castrejon, Durusu-Tanriover, Pincus: EULAR 2010

>50%: 20-50%: <20%:

Standardized measurement required for the scientific method in medicine

• A patient with hypertension, diabetes, osteoporosis, etc. goes to the doctor to find out how she/he is doing, based on “gold-standard” measures by the doctor.

• A patient with RA goes to the doctor to tell the doctor how she/he is doing.

• Why not record the patient history as standard, “scientific” data?

Indices to assess patients with RACore set measure DAS28 1 CDAI 2 RAPID3 3

# 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 0-30

1. Prevoo MLL, et al. Arthritis Rheum 1995;38:44-8.2. Aletaha D, Smolen J. Clin Exp Rheumatol 2005;23:S100-8.3. Pincus T, et al. J Rheumatol. 2008;35: 2136-47.DAS = Disease Activity Score, CDAI = Clinical Disease Activity Index.

Why aren’t laboratory tests the best quantitative measures to assess,

monitor and treat-to-target patients with rheumatoid

arthritis as in patients with diabetes or hyperlipidemia?

"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

ESR Values in Patients With RA Wolfe F, Michaud K, J Rheumatol.

1994;21:1227–1237. Wichita KS, USA

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 NA 26

Nancy, France2 1996 135 NA 29

Groningen, Netherlands2 1996 283 NA 28

Belfast, N Ireland2 1996 51 NA 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:

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. Arthritis Rheum 2009;60(Suppl):S160

5-Year Survival in 206 Patients With RA: Cohort #2 – 1985-1990

100100

0000 1212 2424 3636 4848 6060

Months After BaselineMonths After Baseline

Rheumatoid FactorRheumatoid Factor

Absent (29)Absent (29)

Present Present (175)(175)

100100

0000 1212 2424 3636 4848 6060

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

Multi-Dimensional

Health Assessment

Questionnaire (MDHAQ) Page 1

Some Limitations of Laboratory Tests in RA

1. Normal in 30-50% of patients who require treatment for RA

2. Often not available at time of clinical decision

3. Add to costs needed for therapy

Why isn’t a joint count the best

quantitative measure in RA?

Joint counts in RA Joint exam needed for diagnosis Joint count is the most specific measure of RA

status. The most specific measure may not be the most

informative measure. Poorly reproducible by different observers - must

be done by same observer – not GP, infusion, etc. Most likely to improve with placebo Rigorous formal joint count not performed at

most visits

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

RAPID3 versus DAS28 and CDAI in 285 RA patients

Spearman correlation rho = 0.657

Pincus T, et al. J Rheumatol. 2008; 35: 2136-47

Spearman correlation rho = 0.738

DAS28 CDAI

Pincus T, et al. Arthritis Care Res 2011; 63:1142–1149

Spearman’s correlations of RAPID3 scores with DAS28–ESR scores and CDAI scores at 52 weeks in

982 patients in the RAPID1 clinical trial of CZP vs PBO

p <0.001 for both correlations

DAS28, CDAI and RAPID3 Categories

Activity levelDAS28(0-10)

CDAI(0-76)

RAPID3(0-30)

High - change therapy or have a good reason not to

> 5.1 > 22 > 12

Moderate - strongly consider change 3.2-5.1 10.1-22 6.1-12

Low – change likely not needed 2.6-3.2 2.9-10 3.1-6

Near remission 2.6 2.8 3

Pincus T, et al. Rheum Dis Clin N Am. 2009;35:819-827.

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 RheumatologistsQuestion for Rheumatologists

Segurado and Pincus, 2006. Ann Rheum Dis 65:820-822.

Time to Score RA Measures - Seconds

9.6 4.6

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

A simplified twenty-eight joint quantitative articular

index in rheumatoid arthritis

HA Fuchs, RH Brooks, LF Callahan, T Pincus.

Arthritis Rheum 1989;32:531–537.

T Pincus

J Rheumatol. 33:834-837, 2006

The DAS is the most specific measure, but a patient questionnaire is the most informative

measure to assess rheumatoid arthritis.

Some approaches to overcome limitations of joint counts in RASome approaches to overcome limitations of joint counts in RA

1. All visits must include a careful joint examination, but not formal joint count

2. A RADAI self-report joint count may perform well to characterize joint involvement

3. Can a patient global score for inflammation, as well as damage, and neither (fibromyalgia/somatization), provide clinically useful quantitative data from a health professional?

RADAI Self-report Joint CountRADAI 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 Mild Moderate Severe

a.LEFT FINGERS 0 1 2 3 i.RIGHT FINGERS 0 1 2 3 b.LEFT WRIST 0 1 2 3 j.RIGHT WRIST 0 1 2 3 c.LEFT ELBOW 0 1 2 3 k.RIGHT ELBOW 0 1 2 3 d.LEFT SHOULDER 0 1 2 3 l.RIGHT SHOULDER 0 1 2 3 e.LEFT HIP 0 1 2 3 m.RIGHT HIP 0 1 2 3 f.LEFT KNEE 0 1 2 3 n.RIGHT KNEE 0 1 2 3 g.LEFT ANKLE 0 1 2 3 o.RIGHT ANKLE 0 1 2 3 h.LEFT TOES 0 1 2 3 p.RIGHT TOES 0 1 2 3

q.NECK 0 1 2 3 r.BACK 0 1 2 3

Multi-Dimensional

Health Assessment

Questionnaire (MDHAQ) Page 1:

Foundation for “evidence-

based” visit

Multi-Dimensional

Health Assessment

Questionnaire (MDHAQ) Page 1:

Foundation for “evidence-

based” visit

RADAI vs Core Data Set measures (n=274)RADAI vs Core Data Set measures (n=274)RADAI SJC 28 TJC 28 ESR

RADAI --- 0.42 0.55 0.13*

Swollen 28 JC 0.42 --- 0.55 0.23

Tender 28 JC 0.55 0.55 --- 0.32

MDGlobal VAS 0.52 0.74 0.57 0.26

ESR 0.13* 0.23 0.32 ---

CRP 0.08*** 0.18** 0.21 0.50

FN MDHAQ 0.68 0.47 0.52 0.25

Pt Global VAS 0.69 0.36 0.53 0.21

Pain VAS 0.71 0.39 0.56 0.21

Adjusted for age, disease duration, education and center, All p<0.0001, except *p=0.035, **p=0.003, ***p>0.05

Four 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?

Why isn’t a radiograph the best

quantitative measure in RA?

Radiographs in RA Only pathognomonic feature of RA Permanent record of patient status Excellent quantitative scoring methodsBut Poorly reproducible–several readers Not scored in usual care Less sensitive than ultrasound, MRI Limited prognostic significance for work

disability, mortality

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

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)

MTX and radiographic progression“When used as monotherapy, the structure-

sparing effects of MTX is quite modest compared with that of TNF blockers, even if MTX is used in DMARD-naïve patients.”

Schett et al. Arthritis Rheum 2008

“…studies of anti-TNF therapy plus MTX, compared with the effect with MTX alone, have shown that although MTX is relatively effective at relieving clinical symptoms, it has little or no effect on underlying radiological progression.”

Emery, McInnes, van Vollenhoven, Kraan. Rheumatology 2008

T Pincus, Y Yazici, MJ Bergman J Rheumatol. 35:1487-1488, 2008

More hotel-based medicine

Another form of “making the same mistakes with increasing confidence over an impressive number of years”

Change in Total Sharp/van der Heijde radiographic scores (0-448) in TEMPO trial over 2 years

Van der Heijde Arthritis Rheum 2006

Evidence from clinical trials and long-term observational studies that

disease-modifying anti-rheumatic drugs slow radiographic progression

in rheumatoid arthritis: updating a 1983 review

T Pincus, G Ferraccioli, T Sokka, A Larsen, R Rau, I Kushner, F Wolfe

Rheumatology 41:1346-1356, 2002

1 1.59 -0.54 0.52 2.8 0.4 3.7 1.3 3 5.70

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)

MRI Can Better Identify Early Bone Erosions than X-ray

Prospective Observation of Predictors of Mortality Over 5 Years in 210 Consecutive

Patients with RA -1985-1990Mean baseline values: DeadAge yrs 55.1 65.5 <0.001

p Value

ARA Functional Class 2.2 2.6 <0.001# Comorbidities 1.1 2.1 <0.001

Walking time 10.8 16.8 <0.001

ESR 33.8 48.3 0.004

ADL score 1.98 2.32 0.005

Learned helplessness 2.41 2.55 0.007

Global self-report 2.6 3.0 0.01

# Extra-articular features 0.2 0.5 0.02

Duration of disease 9.1 12.7 0.03

Years of education 10.8 9.4 0.03

Joint count 12.8 15.9 0.04

Radiograph score 1.2 1.4 0.20

Rheumatoid factor titer 2.7 2.9 0.28

Pain-Visual analog scale score 5.40 5.19 0.68

Callahan et al, Arthritis Care Res 10:381,1997

Prospective analysis of predictors of mortality over 5 years in 210 consecutive patients with RA: Cox proportional hazards model including demographic, disease, patient questionnaire,

laboratory, joint count, and X-ray variables

Callahan, et al Arthritis Care Res 10:381,1997

----0.171.40X-ray

----0.04 1.03*Walking time

----0.101.02Joint count

---- 0.005 1.01*ESR

---- 0.007 0.89*Education

----0.02 1.04*Disease duration

0.021.76* 0.002 2.00*MHAQ ADL score*

0.021.40*<0.001 1.63*Comorbidity

<0.0011.06*<0.001 1.07*Age

P ValueRelative RiskP ValueRelative Risk

Stepwise ModelUnivariable Models

MHAQ=Modified Health Assessment Questionnaire, ADL=Activities of Daily Living, *= Confidence Interval does not cross 1.00

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)

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

Radiographs ESR, CRP

Shared epitope

Rheumatoid factorJoint deformity

Duration of disease

Functional disabilityPainPatient global

Joint tendernessFatigueAge

Strongly and weakly correlated measures to assess rheumatoid arthritis

ESR=erythrocyte sedimentation rate; CRP=C-reactive protein.

Sokka & Pincus Best Pract Res Clin Rheumatol 2007;21:653-661

Joint swelling

What about patient and physician global

measures as quantitative

measures in RA?

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

Relative efficiencies of 7 RA Core Data Set measures in 4 adalimumab clinical trials

ARMADA DE011 DE019 STAR

Tender Joint CountSwollen Joint Count

Assessor GlobalCRP

Function (HAQ)Pain

Patient Global

Pincus, Amara, Segurado, Bergman, Koch, J Rheumatol 35:201-205, 2008

How to collect quantitative patient history data as

standardized “scientific data using the

MDHAQ/RAPID3?

Let the patient do most of the work! Most patients are more accurate about many details of their own medical history than health professionals

MDHAQ helps the patient prepare for a better visit

MDHAQ/RAPID3Advantages to patient

• Prepares patient for encounter

• Simple format for patient to communicate level of pain, fatigue, function, exercise, symptoms

• Quantitative data for any doctor – not restricted to specific rheumatologist

• “Benchmark” to compare to future visits

• Assures inclusion of important patient symptoms and recent medical history

Doctor reviews information with the patient,and interprets data for clinical decisions

MDHAQ/RAPID3Advantages to doctor

• Saves time – especially recent history, symptom review, self-report joint count

• Doctor is not measurer but interprets measures

• Specific doctor not required, unlike joint count

• Familiar, standard format for patient data

• Quantitative data for “treat to target” strategy

• Clues to possible fibromyalgia/distress

• MDHAQ – all key data on one page

• “Benchmark” to document future status

• “Checklist” documentation of patient status

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

RA 61 yo M (#9) Onset: 01/1996 Visit 1: 11/4/03

Visit Date 11/4/03

Q-Function (0-10) 2.7

Q-Pain (0-10) 9.6

Q-Global (0-10) 8.9

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 drug, C = change in dose, T = taper, D/C = discontinue

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

Visit 2 - 4 Nov 2003

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

L-ESR 43 8

T-Prednisone N3qd 3qd

T-Methotrexate N10qw C20qw

T-Folic acid N1qd 1qd

T-acetamnphn/codn 30tid 30tid

T-Naproxen 880q6h 440bid

Visit 4 - 28 Sep 2004

Visit Date 4Nov03 13Jan04 20Apr04 28Sep04

Q-Function (0–10) 2.7 0 0.3 0

Q-Pain (0–10) 9.5 0.5 0.0 0.5

Q-Global (0–10) 9.0 0.5 0.5 1.0

RAPID3 (0–30) 21.2 1.0 0.8 1.5

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-acetamnphn/codn 30tid 30tid D/C

T-Naproxen 880q6h 440bid prn prn

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

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-acetamnphn/Codn 30tid 30tid D/C

T-Naproxen 880q6h 440bid prn prn prn

T-Adalimumab N40qow

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

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-acetamnphn/codn 30tid 30tid D/C

T-Naproxen 880q6h 440bid prn prn prn D/C

T-Adalimumab N40qow 40qow

N=new drug, C=change in dose, T=taper, D/C=discontinue

Patients seen for standard rheumatoid arthritis care have significantly better articular, radiographic,

laboratory, and functional status in 2000 than in 1985

T Pincus, T Sokka, H Kautiainen

Arthritis Rheum 52:1009-1019, 2005

20001985

0 5 10 15Disease Duration (Years)

Disease Duration (Years)

0.020 0 5 10 15 20

Cross-Sectional Data: All RA Patients seen by TP in 1985 (n=125) and in 2000 (n=150):

Pincus, Sokka, Kautiainen, Arthritis Rheum 52:1009, 2005

Multidimensional Health Assessment Questionnaire (MDHAQ) scores

20001985

0 5 10 15Disease Duration (Years)

Disease Duration (Years)

20 0 5 10 15 20

Swollen Joint Count Scores

Larsen X-Ray score,% of Maximum

0 5 10 15

Disease duration

0 5 10 15

Disease duration

1985 2000

Methotrexate in RA Care: 1980-2005Jyvaskyla, Finland & Nashville, TN

Sokka and Pincus. Rheumatology (Oxford). 2008:47:1543-1547

Quantitative target values of predictors of mortality in

rheumatoid arthritis as possible goals for therapeutic interventions:

an alternative approach to remission or ACR20 responses?

T Pincus, T Sokka

J Rheumatol 28:1723-1734, 2001.

Larsen radiographic scores in 295 patients inJyväskylä, Finland, 5 years after presentation (dx),

according to the period of presentation

Sokka T, Pincus T. Rheumatology (Oxford) 2008; 47:1543-7

Patient functional status according to (a) MHAQ physical function score and (b) pain,

in 596 patients in Nashville, TN, USA at final visit, according to the period when last visit occurred

Sokka T, Pincus T. Rheumatology (Oxford) 2008; 47:1543-7

Methotrexate as the “anchor drug” for the treatment of early rheumatoid arthritis.

T Pincus, Y Yazici, T Sokka, D Aletaha, JS Smolen

Clin Exp Rheumatol 21:S179-S185, 2003.

Goodman and Gilman Textbook of Pharmacology, 2006 edition:

"Although aspirin is regarded as the standard against which other drugs should be compared for the treatment of rheumatoid arthritis, many clinicians favor the use of other NSAIDs perceived to have better gastrointestinal tolerability, even though this perception remains unproven by convincing clinical trials.

Patients with progressive or resistant disease require therapy with more toxic, second-line drugs, such as antimalarials, glucocorticoids, methotrexate, or immunosuppressive agents.

– (Section IV/Chapter 26, page 690)

Is weekly low-dose methotrexate one of the safest medications available in clinical medicine, far safer than (almost) all antibiotics, anti-depressants, statins, etc.?

T Pincus, TWJ Huizinga, Y Yazici

J Rheumatol. 34:250-252, 2007

Medication

All 4,363 patients in

15 countries

301 Danish patients

Prednisone Ever 66% 43%

Methotrexate Ever 83% 85%

Leflunomide Ever 21% 11%

Sulfasalazine Ever 43% 64%

Biological Agent Ever 23% 23%

QUEST-RA: Medications inQUEST-RA: Medications in4,363 patients in 15 countries4,363 patients in 15 countries

Sokka, Kautiainen, Toloza, Mäkinen, Verstappen, Lund, Hetland, et al. QUEST-RA: Ann Rheum Dis 66:1491-1496, 2007.

Mean and median initial prednisone dose in 308 patients with rheumatoid arthritis (RA) seen from 1980 through 2004, computed in 5-year periods

5.14.1

3.65 5 5

1980-84 1985-89 1990-94 1995-99 2000-04

Mean Median

1980-84N = 37

1985-89N = 74

1990-94N = 77

1995-99N = 61

2000-04N = 59

Percent change () over 12 and 24 months in MDHAQ-FN (0-10) in 308 patients treated with prednisone 1980-2004

(“+” indicates improvement and “-” worsening)

YearFirst Seen N

Initial dose <5 mg/d Initial dose 5 mg/d

Baseline FN

1980-84 37 None -- -- 4.1 +33% +32%

1985-89 74 1.4 -5% -20% 3.3 +45% +26%

1990-94 77 1.7 +26% +46% 3.2 +44% +38%

1995-99 61 2.7 +33% +14% 3.9 +27% +28%

2000-04 59 2.6 +37% +29% 4.3 +25% +33%

TOTAL 308 2.4 +34% +24% 3.5 +40% +31%

Editorial:Are long-term very low doses of

prednisone for patients with rheumatoid arthritis as helpful as

high doses are harmful?

T Pincus, T Sokka, CM Stein

Ann Internal Med 136:76-78, 2002

Clinical trial results in 31 participants who were randomized to prednisone or placebo, following gradual withdrawal of

prednisone, according to baseline prednisone dose

Baseline prednisone dose

Study group Clinical trial results 1 mg 2 mg 3 mg 4 mg Total

Prednisone Number randomized 1 2 10 2 15

Withdrew – lack of efficacy 0 0 3 0 3*

Completed trial 1 2 6 1 10*

Withdrew – administrative 0 0 1 1 2

Placebo Number randomized 0 1 12 3 16

Withdrew – lack of efficacy 0 1 9 1 11*

Completed trial 0 0 2 2 4*

Withdrew – administrative 0 0 1 0 1

TOTAL 1 3 22 5 31

*For 28 participants who either completed the trial or withdrew because of lack of efficacy, p = 0.021 For all 31 randomized participants, p= 0.032 by Fisher's exact test (prednisone vs placebo).

Pincus T, Luta G, Swearingen CJ. Ann Rheum Dis. 2009 ;68(11):1715-20.

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

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

MDHAQ/RAPID3 in Clinical Rheumatology• MDHAQ – not joint count, X-ray, or lab test – best predictor

of work disability, death in RA• RAPID3 distinguishes active treatment from placebo as

efficiently as DAS28, CDAI• Useful in all rheumatic diseases –

NSAID from acetaminophen in OA vs WOMAC fibromyalgia from RA vs ESR

• Identify incomplete response to Mtx, biologic• Completed before visit - prepares patient• RAPID3, recent history and review of systems save time for

doctor – improve documentation• Flow sheets are very helpful• Does not replace history and physical exam• Does not prevent joint count imaging, etc.

Why is quantitative standardized measurement advantageous in usual clinical care?

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