DAS 28 in clinical practiceSpeaker – Date – Place

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DAS 28 in clinical practice

Introduction – Disease activity scoring

DAS 28 components

Formula's

DAS 28 segments

Response criteria

DAS 28 in current clinical practice

Importance of low disease activity

Discussion

Presentation of DAS 28 exercise

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Introduction Disease Activity Scoring

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The DAS score

Main reason for introduction of a standardised scoring system for RA disease activity: need for uniformity in the interpretation of RA clinical trial data and individual patient outcomes

DAS was introduced in 1983 (originally, 44 articulations were scored)

DAS 28, apart from other paramaters, scores tenderness and swelling in a limited number of joints

DAS 28 is fast, easy to use and as valid as more comprehensive joint counts

Change in disease activity (DAS) over time compared to baseline allows estimation of response (EULAR response criteria)

Source: www.das-score.nl

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DAS 28 components

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Components of DAS 28 scoreJOINTS

SJC

Number of Swollen Joints out of 28 joints: shoulders, elbows, wrists, MCP joints, PI joints and knees

TJC

Number of Tender Joints out of 28 joints

Source: Eular handbook of clinical assessments in RA – Third edition

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Components of DAS 28 scoreJoint ASSESSMENT TECHNIQUE

Swelling (SJC):

Soft tissue swelling, detectable along the joint margin

Synovial effusion invariably means the joint is swollen

Bony swelling or deformity, or oedema surrounding the joints do not constitute joint swelling

Fluctuation is a characteristic feature of swollen joints

Joint swelling may influence the range of joint movement (for example decreased dorsiflexion of the wrist, or decreased elbow extension). This can be useful in determining the presence of swelling

Source: Eular handbook of clinical assessments in RA – Third edition

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Components of DAS 28 scoreJoint ASSESSMENT TECHNIQUE

Tenderness (TJC):

Pain in a joint under defined circumstances, including:

Pain at rest with pressure (for example MCP and wrist joints)

Pain on movement (for example shoulders)

From questioning about joint pain

Pressure to elicit tenderness should be exerted by the examiner's thumb and index finger, sufficient to cause 'whitening' of the examiner's nail beds

Source: Eular handbook of clinical assessments in RA – Third edition

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Components of DAS 28 scoreESR or CRP

ESR (erythrocyte sedimentation rate) in mm/hUnspecific marker of inflammatory processes

Normal range: 1-15 mm/h (slightly higher in women)

Also increased in AID, like RA, or in case of malignancy

Reflects disease activity of the past few weeks

CRP (C-reactive protein) in mg/LSensitive marker of inflammatory processes

Normal range: below 3 mg/L

Less susceptible to disturbing factors than ESR

Better reflects short-term changes

Shorter waiting time for lab result

Source: Eular handbook of clinical assessments in RA – Third edition

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Components of DAS 28 scoreVisual Analogue Scale (VAS)

Scale of 100 mm

Range: 0-100

Reflects perception by your patient of global disease activity

Source: Eular handbook of clinical assessments in RA – Third edition

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DAS 28 Formula's Disease activity segmentsResponse criteria

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Validated formula's depending on availability of data….

DAS 28 ESR 40.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*Ln(ESR) + 0.014*VAS

DAS 28 ESR 3 (no VAS)[0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*Ln(ESR)]*1.08 + 0.16

DAS 28 CRP 4 (CRP)0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*VAS + 0.96

DAS 28 CRP 3 (CRP, no VAS)[0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1)]*1.10 + 1.15

Note: VAS in mm ! (0-100) CRP in mg/L (lab values mostly given in mg/dL)

Source: Eular handbook of clinical assessments in RA – Third edition

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Linking DAS 28 and DAS 44

The following formula allows to indirectly calculate DAS 28 values from known (historical) DAS (44) values:

DAS 28 = (1,072 x DAS 44) + 0,938

Range DAS: 1-9

Range DAS 28: 2-10

Source: Eular handbook of clinical assessments in RA – Third edition

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2,6

3,2

5,1

0

1

2

3

4

5

6

7

8

9

10

DA

S 2

8 S

CO

RE

High Activity

Medium Activity

Low Activity

Remission

Validated DAS 28 segments according to disease activity

Therapeutic goal

Source: www.das-score.nl

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EULAR response criteria

DAS improvement

DAS at endpoint

DAS 28 at endpoint

> 1.2 0.6 – 1.2 ≤ 0.6

≤ 2.4 ≤ 3.2 low

disease activity

Good response

Moderate response

No response

2.4 – 3.7 3.2 – 5.1 medium

disease activity

Moderate response

Moderate response

No response

> 3.7 > 5.1 high

disease activity

Moderate response

No response

No response

Source: Eular handbook of clinical assessments in RA – Third edition

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EULAR response criteria

The EULAR response criteria are based on attained level of DAS 28 (at endpoint) – corresponding with the discussed disease activity segments (low, medium, high) …

and classify patients as :

good

moderate

or non-responders

depending on the DAS improvement since baseline

Source: Eular handbook of clinical assessments in RA – Third edition

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DAS 28 in current clinical practice

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Median DAS 28 score in RA patients per COUNTRY (2005-2006)

Source: Sokka 2007 – Ann Rheum Dis 66; 407-409

Assessment period: Jan 2005-Oct 2006

0,00

0,50

1,00

1,50

2,00

2,50

3,00

3,50

4,00

4,50

5,00

Denmar

k

Finlan

d

Franc

e

Germ

any

Irelan

dIta

ly

Nether

lands

Spain

Sweden UK

SJC 28

TJC 28

DAS 28

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Median DAS 28 score > 3.2 means…

PROBABLY MORE THAN 50% OF PATIENTS HAVING DAS 28 SCORES OF > 3.2 !!!

Interpretation median DAS 28 scores

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26%

13%

43%

19%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

High Activity DAS ≥ 5.1

Medium Activity DAS 3.2 < 5.1

Low Activity DAS 2.6 < 3.2

Remission DAS < 2.6

% of RA patients in each DAS 28 segment(2006)

Roche market research – data on file – data collection period: 2006

Undertreated !

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Severity as perceived by physician compared per DAS 28 – segment (2006)

N = 3.878 patients with disease severity and DAS score stated

486191

427107

406

224

878

304

108 75345

327

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Severe/Terminal

Moderate

Mild

Underestimated

Remission DAS < 2.6

Low activity DAS 2.6-3.2

Med activity DAS 3.2-5.1

High activity DAS > 5.1

19%43%13%26%

Undertreated !

Roche market research – data on file – data collection period: 2006

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DAS 28 Importance of low disease activity as a therapeutic goal

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From DAS to DIS

Disease activity

Joint damage

Disability

(1,3)

(2,3)

(1) Smolen 2004 – Ann Rheum Dis 63: 221-225

(2) Scott 2000 – Rheumatology 39: 122-132

(3) Welsing 2001 – Arthritits Rheum 44: 2009-2017

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From DAS to DIS

Erosions develop in 10-26% of patients with RA within 3 months from onset of the disease

Even "mild" disease activity is still active disease and may be slowly leading to significant joint destruction and disability.

Therefore, the most important aim in RA treatment is remission

Patients need to be monitored every 2-3 months, as long as they do not reach a state of "no evidence of active disease", in order that the switch of therapeutic strategies can be timely

Smolen 2004 – Ann Rheum Dis 63: 221-225

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“spikes” of disease activity

0

1

2

3

4

5

6

0 3 6 9 12 15 18

Time on therapy

DA

S s

core

21 24

High level of joint destruction

Low level of joint destruction

Adapted from: Grigor C et al. Lancet, 2004;364:263-9

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Treatment based on DAS28 targeting low disease activity (DAS 28 < 3.2)

Source: www.das-score.nl

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Linking DAS and Radiological progression

DAS improvement

(DAS 28 at endpoint)

DAS at endpoint

> 1.2 0.6 – 1.2 ≤ 0.6

≤ 3.2 ≤ 2.4

3.2 – 5.1 2.4 – 3.7

> 5.1 > 3.7NON RESPONDERS

RX PROGRESSION

NO RX PROGRESSION

Svensson 2000 – Rheumatology 39: 1031-1036

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Linking DAS and Radiological progression

29% of patients, classified as responders, had end-point DAS of > 2.4 (corresponding to a DAS 28 of 3.2 according to the EULAR criteria), indicating moderate or high remaining disease activity

In this group, significant X-ray progression occured, while there was no evident progression in the group of responders (71%) having a final DAS lower than 2.4

In other words: response to treatment (good or moderate) is not enough to avoid progression of joint damage. DAS28 values lower than 3.2 should be targeted

Svensson 2000 – Rheumatology 39: 1031-1036

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MabThera treatment allows to reach those goals…

-2,39

-2,94-3,1

-3,5

-3

-2,5

-2

-1,5

-1

-0,5

0

1st course 2nd course 3rd course

Week 24, n=97

Mea

n D

AS

28 c

han

ge

fro

m

ori

gin

al b

asel

ine

Vs original baseline

Keystone et al. EULAR 2007 – SAT 0012

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Mea

n c

han

ge

fro

m b

asel

ine

2,31

0,99

1,32

1

0,410,59

0,0

0,5

1,0

1,5

2,0

2,5

Mean change in totalSharp–Genant score

Mean change in joint spacenarrowing score

Mean change in erosionscore

Placebo (n=184) Rituximab 1000 mg x 2 (n=273)

p=0.0046

p=0.0006

p=0.0114

…which is indeed reflected in significantly better RX scores

Patients with initial and at least 1 follow up with linear extrapolation as required

SPC 2007 - Keystone et al. EULAR 2006 – OP 0016

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Questions or Remarks ?