DAS 28 in clinical practice Speaker – Date – Place

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

Introduction Disease Activity Scoring

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

DAS 28 components

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

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

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

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

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

DAS 28 Formula's Disease activity segments Response criteria

Validated formula's depending on availability of data…. DAS 28 ESR 4 0.56*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

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

Validated DAS 28 segments according to disease activity Therapeutic goal Source: www.das-score.nl

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 > 3.7 > 5.1 high disease activity Source: Eular handbook of clinical assessments in RA – Third edition

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

DAS 28 in current clinical practice

Median DAS 28 score in RA patients per COUNTRY (2005-2006) Assessment period: Jan 2005-Oct 2006 Source: Sokka 2007 – Ann Rheum Dis 66; 407-409

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 !!!

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

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 2.6-3.2 Med activity DAS 3.2-5.1 High activity DAS > 5.1 N = 3.878 patients with disease severity and DAS score stated Roche market research – data on file – data collection period: 2006

DAS 28 Importance of low disease activity as a therapeutic goal

Disease activity Joint damage Disability From DAS to DIS (1,3) (2,3) Smolen 2004 – Ann Rheum Dis 63: 221-225 Scott 2000 – Rheumatology 39: 122-132 Welsing 2001 – Arthritits Rheum 44: 2009-2017

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

“spikes” of disease activity 1 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

Treatment based on DAS28 targeting low disease activity (DAS 28 < 3 Source: www.das-score.nl

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: 1031-1036

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

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

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

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