1. DAS 28 in clinical practice
Speaker – Date – Place

2. 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

3. Introduction Disease Activity Scoring

4. 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:

5. DAS 28 components

6. Components of DAS 28 score JOINTS
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

7. Components of DAS 28 score Joint 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

8. Components of DAS 28 score Joint 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

9. Components of DAS 28 score ESR or CRP
ESR (erythrocyte sedimentation rate) in mm/h
Unspecific 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/L
Sensitive 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

10. Components of DAS 28 score Visual 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

11. DAS 28 Formula's Disease activity segments Response criteria

12. Validated formula's depending on availability of data….
DAS 28 ESR 4
0.56*sqrt(TJC28) *sqrt(SJC28) *Ln(ESR) *VAS
DAS 28 ESR 3 (no VAS)
[0.56*sqrt(TJC28) *sqrt(SJC28) *Ln(ESR)]*
DAS 28 CRP 4 (CRP)
0.56*sqrt(TJC28) *sqrt(SJC28) *ln(CRP+1) *VAS
DAS 28 CRP 3 (CRP, no VAS)
[0.56*sqrt(TJC28) *sqrt(SJC28) *ln(CRP+1)]*
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

13. 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

14. Validated DAS 28 segments according to disease activity
Therapeutic goal
Source:

15. EULAR response criteria
DAS improvement
DAS at endpoint
DAS 28 at endpoint
> 1.2
0.6 – 1.2
≤ 0.6
≤ 2.4
≤ low disease activity
Good response
Moderate response
No response
2.4 – 3.7
3.2 – 5.1 medium disease activity
> 3.7
> high disease activity
Source: Eular handbook of clinical assessments in RA – Third edition

16. 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

17. DAS 28 in current clinical practice

18. Median DAS 28 score in RA patients per COUNTRY (2005-2006)
Assessment period: Jan 2005-Oct 2006
Source: Sokka 2007 – Ann Rheum Dis 66;

19. Interpretation median DAS 28 scores
Median DAS 28 score > 3.2 means…
PROBABLY MORE THAN 50% OF PATIENTS HAVING DAS 28 SCORES OF > 3.2 !!!

20. % of RA patients in each DAS 28 segment (2006)
Undertreated !
Roche market research – data on file – data collection period: 2006

21. N = 3.878 patients with disease severity and DAS score stated
Severity as perceived by physician compared per DAS 28 – segment (2006)
Undertreated !
26%
13%
43%
19%
Underestimated
Remission DAS < 2.6
Low activity DAS
Med activity DAS
High activity DAS > 5.1
N = patients with disease severity and DAS score stated
Roche market research – data on file – data collection period: 2006

22. DAS 28 Importance of low disease activity as a therapeutic goal

23. Disease activity Joint damage Disability From DAS to DIS (1,3) (2,3)
Smolen 2004 – Ann Rheum Dis 63:
Scott 2000 – Rheumatology 39:
Welsing 2001 – Arthritits Rheum 44:

24. 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:

25. “spikes” of disease activity1 2 3 4 5 6 9 12 15 18
Time on therapy
DAS score 21 24
High level of joint destruction
Low level of joint destruction
Adapted from: Grigor C et al. Lancet, 2004;364:263-9

26. Treatment based on DAS28 targeting low disease activity (DAS 28 < 3
Source:

27. 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
> 3.7
NO RX PROGRESSION
RX PROGRESSION
NON RESPONDERS
Svensson 2000 – Rheumatology 39:

28. 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:

29. MabThera treatment allows to reach those goals…
Mean DAS28 change from
original baseline
Vs original baseline
Week 24, n=97
Keystone et al. EULAR 2007 – SAT 0012

30. …which is indeed reflected in significantly better RX scores
p=0.0046
p=0.0114
Mean change from baseline
p=0.0006
Patients with initial and at least 1 follow up with linear extrapolation as required
SPC Keystone et al. EULAR 2006 – OP 0016

31. Questions or Remarks ?