1. Remission in Established RA Patients
EULAR 2004 Final Show
Remission in Established RA Patients

2. Definition of Remission
Clinical Remission
ACR/DAS criteria, or normal acute phase response, no clinical synovitis
Imaging Remission
No radiographic damage progression
No significant synovitis on sensitive imaging
True Remission
A state of low disease activity with no progression of structural damage

3. New Therapeutic Possibilities for RA – Remission is a Realistic Goal
Tools
Optimized MTX
Combination therapy
Anti-TNF therapy
Processes
Early treatment
Avoid treatment delay
Take advantage of “window of opportunity”
Patient monitoring
DAS

4. Clinical Remission by DAS28
DAS28 Score
Disease Activity
Severe
5.1
Moderate
3.2
Low
2.6
Remission
DAS28 <2.6
Based on VAS of 100mm
Prevoo MLL et al. Arthritis Rheum 1995;38:44-8. van Gestel AM et al. J Rheumatol 1999;26:

5. Remission in RA Importance of Structural Damage
Determinants of Structural Damage
Interrelationship synovitis and damage
Remission Clinical and Imaging
Impact of DMARDs
Effect of TNF antagonists

6. Why Is Structural Damage Important?
EULAR 2004 Final Show
Why Is Structural Damage Important?
Cummulative measure, reflects disease control
Surrogate marker for long-term outcome (physical function, employment)
In cohorts ~ stable disease activity
Very slow increase in HAQ score
Constant progression in structural damage

7. ACR Goals of Therapy in RA
EULAR 2004 Final Show
ACR Goals of Therapy in RA
Symptom relief
Improvement in physical function
Reduce physical disability
Slowing/arresting progression of structural damage
Highlights:
Goals of therapy are to attain symptomatic relief of disease activity including the swelling and tenderness of joints, as well as the pain patients with active RA experience.
Improving the physical function and physical capabilities of the patient.
Thirdly, advanced therapies should intervene in slowing the progression of the disease.
Guidelines for the Management of RA. Arthritis Rheum. 1996; 39:

8. Schematic Representation of the Course of RA Over 30 Years
EULAR 2004 Final Show
Inflammation
Disability
Radiographic Scores
Kirwan J. J Rheumatol. 1999;26:720-5.

9. Relationship Between X-ray Progression and Physical Function - TEMPO Trial
EULAR 2004 Final Show
X-ray progression and HAQ scores were determined at baseline, Year 1 and Year 2
After adjustment for co-variates, Sharp-score was a statistically significant determinant of HAQ-score (p<0.0001)
Progression of radiographic damage over a relatively short period of time leads to deterioration of physical function
The purpose of this study was to investigate the longitudinal relationship between function and the level of radiographic damage as well as radiographic progression after adjustment for age, sex and disease activity in patients with early or advanced RA.
 The 2-year TEMPO database (baseline, 1-year, and 2-year data) was used for this analysis. Physical function was measured by the HAQ-score, and radiographic damage was measured on radiographs of hands and feet by the vanderHeijde-modified Sharp score, at baseline, 6 months, 1-year, and 2-year time points. HAQ-score was modeled by age, sex, treatment, disease activity (DAS as well as CRP), and Sharp-score or progression in Sharp-score (interval 0-1 year and 1-2 year) by generalized mixed linear modeling (GMLM) in order to adjust for within-patient correlation.
 After adjustment for age, sex, and disease activity, Sharp-score appeared to be a statistically significant determinant of HAQ-score (p<0.0001). The effect of change in radiographic damage on physical function showed a clear trend toward increasing HAQ scores with increasing radiographic damage progression. Patients with negative progression scores would appear to have lower levels of HAQ compared with patients with positive progression scores.
 This analysis proves the longitudinal relationship between radiographic damage and physical function:
·         Increasing radiographic damage is associated with increasing limitation in physical function
·         Progression of radiographic damage over a relatively short period of time leads to deterioration of physical function
·         Patients with negative progression scores show better physical function than patients with zero- or positive progression scores
 Inhibition of radiographic progression is an important and relevant goal. Since small increase in radiographic damage can be assessed reliably, radiographic damage is a good outcome measure in clinical trials.
Reference:
van der Heijde D, et al. The level of radiographic damage and 2-year radiographic progression are determinants of physical function. A longitudinal analysis in the TEMPO trial. ACR 2005, Abstract 1456
Negative Zero Mild Severe
Progression
van der Heijde D, et al. Abstract 1456, ACR 2005.

10. Cumulative Probability Plot of Radiographic Progression
EULAR 2004 Final Show
Moderate
Progression
Unchanged
Lower Score

11. Cumulative Probability Plot of Radiographic Outcome
EULAR 2004 Final Show
Cumulative Probability Plot of Radiographic Outcome
Rapid Progressors
Rapid Progression
Moderate
Progressors
Unchanged
Lower Score

12. What Factors Will Predict Persitemt and Erosive RA?
EULAR 2004 Final Show
Visser et al, Arth Rheum, Feb 2002

13. Stepwise Logistic Regression Analysis of Predictive Factors of Radiographic Progression
EULAR 2004 Final Show
Conclusion: early destruction, high ESR, IgM RF positivity and DR type predict destruction during 3 years of disease
Combe B, et al: Arthritis Rheum. 2001;44:

14. Treatment Goals for RA Today
EULAR 2004 Final Show
Treatment Goals for RA Today
TREAT EARLY
Any delay impacts on outcomes
TREAT OPTIMALLY
Combination of traditional DMARDS
TARGET CLINICAL REMISSION
Targeted outcomes / Tight control
EARLY USE OF BIOLOGICS
Quality of life is probably the most important factor for patients. No matter what a drug may be doing to slow down progression of a disease, patients who do not feel better on a day-to-day basis or who fail to improve their ability to carry out activities of daily living will be unlikely to continue taking the drug. HR-QOL is categorized under the Health Assessment Questionnaire (HAQ), a commonly used self-report measure of physical status. Within the standard HAQ are HR-QOL parameters, such as level of disability, pain, mental health, social status, and vitality.

15. Very Early DMARD Intervention Improves Outcomes
Delayed treatment (median treatment lag time, 123 days; n=109)
Early treatment (median treatment lag time, 15 days; n=97)
Median Sharp Score *
*P<0.05 vs delayed-treatment group.
Lard LR et al. Am J Med. 2001;111:

16. TICORA Study of Intensive vs Routine Treatment: DAS Scores
EULAR 2004 Final Show
TICORA Study of Intensive vs Routine Treatment: DAS Scores 6
Routine 5
Intensive 4
*P < 0.001
Mean DAS score 3 * 2 1 3 6 9 12 15 18
Months
Grigor C, et al. Lancet. 2004;364:
132

17. Clinical Results at 18 Months
Aim for a Target –TICORA Trial
TICORA
EULAR 2004 Final Show
Clinical Results at 18 Months
p<0.0001
-3.5
-1.9
Mean Fall in DAS
84%
40%
ACR50
9.3
-0.97
-30
71%
65%
82%
Intensive Care
(n=50)
p=0.021
p=0.0025
p=0.09
P-value
4.0
SF12 Physical Summary Score
-0.47
Change in HAQ
-14
Change in CRP (mg/dL)
18%
ACR70
16%
EULAR Remission
44%
EULAR Good Response (DAS ≤2.4 and fall of 1.2 from baseline)
Routine Care
(n=53)
Results at 18 months showed that intensive care treatment of RA patients with early disease produced better outcomes on all measurements compared to the control group. Intensive care of patients with active RA resulted in substantial improvements in disease activity and significant improvement in outcomes over 18 months. In addition, safety outcomes were better in the intensive care group compared to the routine care group (46 AEs vs.. 85 AEs).
One patient withdrew after randomisation and seven dropped out during the study. Mean fall in DAS was greater in the intensive group than in the routine group (–3·5 vs. –1·9, difference 1·6 [95% CI 1·1–2·1], p<0·0001). Compared with routine care, patients treated intensively were more likely to have a good response (definition, 45/55 [82%] vs. 24/55 [44%], odds ratio 5·8 [95% CI 2·4–13·9], p<0·0001) or be in remission (disease activity score <1·6; 36/55 [65%] vs. 9/55 [16%], 9·7 [3·9–23·9], p<0·0001). Three patients assigned routine care and one allocated intensive management died during the study; none was judged attributable to treatment.
Much debate was raised regarding the reporting of such a high ACR70 (71%) and EULAR remission (65%) response rate in the intensive care-treated group. Such high response rates have not been observed in other trials, including trials evaluating biologics.
Reference: Grigor C, Calpell H, Stirling A, et al, Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 364: , 2004.
Grigor C et al Lancet 2004;364:

18. Radiographic Results at 18 Months
TICORA
Aim for a Target –TICORA Trial
EULAR 2004 Final Show
Radiographic Results at 18 Months
p=0.02
4.5
8.5
Total Sharp score*
3.25
0.5
Intensive Care
(n=50)
p=0.331
p=0.002
P-value
Joint space narrowing* 3
Erosions score*
Routine Care
(n=53)
Reduced progression of erosive disease and total radiographic damage was recorded, but not in joint-space narrowing. The effect on radiographic progression was less striking than that on clinical disease activity, and was less impressive than results obtained in trials of anti-TNF treatment.
The authors suggest that “the speed of disease activity control with anti-TNF treatment could be important, but conventional disease-modifying antirheumatic drugs might simply be less effective in reducing radiographic progression, even when used intensively”.
Reference: Grigor C, Calpell H, Stirling A, et al, Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 364: , 2004.
* Median (IQR) increase in score
Grigor C et al Lancet 2004;364:

19. Control of Structural Damage is Greatest with Continuous Control of Disease Activity*
Const. Low DAS
Fluct. Low DAS
Fluct. High DAS
Const. High DAS
160
140
140
120
120
100
100 80
Sharp Score 80
Sharp Score 60 60 40 40
Baseline
TSS = 20
Baseline
TSS = 0 20 20 3 6 9 3 6 9
Time (Yrs)
Time (Yrs)
* RF Positive Patients
Welsing et al. Arthritis Rheum 2004;50:

20. Does good clinical control translate into NO radiographic progression?

21. Radiological Damage in RA Patients on Sustained Remission Grégory C, et al. Abstract 346, ACR 2006.
EULAR 2004 Final Show
? is their radiological progression over 5-years in recent RA patients with persistent remission (Between Y3 and Y5)
191 RA patients <1 year on SSZ, MTX or Both
Available patients: 134
30 (22.4%) Remission with DAS44 <1.6 at 3 and 5 years
6 (20%) patients had radiographic progression or new erosions between Y3 and Y5

22. Remission on DMARDs DMARDs frequently produce clinical remission
DMARDs rarely produce imaging remission
Hence DMARDs rarely produce true remission
Explains progression of damage in patients in clinical remission on DMARDs?
What happens with TNF antagonists?

23. Predictors of radiographic progression in early RA patients treated with MTX

24. CRP Change And Radiographic Progression - PREMIER Trial
CRP Levels:
% with No Radiographic Progression
van der Heijde DF, et al. Ann Rheum Dis 2005;64(Suppl III):436-7 (SAT0085)

25. CRP Change And Radiographic Progression - PREMIER trial
CRP Levels:
% with No Radiographic Progression
van der Heijde DF, et al. Ann Rheum Dis 2005;64(Suppl III):436-7 (SAT0085)

26. Smolen J et al. Arthritis Rheum 2006;54:702
EULAR 2004 Final Show
Predictors of radiographic progression of patients treated with MTX in the ASPIRE trial
Baseline CRP
Baseline ESR
Week 14 DAS
Mean CRP over 52 weeks
Mean ESR over 52 weeks
Smolen J et al. Arthritis Rheum 2006;54:702

27. DAS28 after 14wks of MTX Tx Predicts Rapid Radiographic Progression
EULAR 2004 Final Show
Disease activity was moderate to high at baseline in all ASPIRE patients in this trial, but it decreased significantly in many patients after 3
months of treatment. This initial treatment response corresponds to a time point when it is recommended that physicians consider changes in DMARD therapy.
If a ERA subject continues to have a DAS28 score > 4 after 14 weeks of MTX 20mg the subject can expect to experience rapid radiographic progression.
Smolen J et al. Arthritis Rheum 2006;54:702

28. Induction and Maintenance of Remission in Early RA

29. Treatment Strategies in Early RA
BeSt
EULAR 2004 Final Show
Treatment Strategies in Early RA
Sequential
MONO-Therapy
STEP-UP
Therapy
Initial COMBO
Therapy
Initial BIOLOGIC
Therapy 1.
MTX
MTX
MTX
+ SSZ + PRED
MTX
+ Biologic 2.
SSZ
MTX
+ SSZ
MTX
+ CSA + PRED
SSZ 3.
LEF
MTX
+ SSZ + HCQ
MTX
+ Biologic
LEF 4.
MTX
+ Biologic
MTX + SSZ
+ HCQ + PRED
MTX
+ CSA + PRED 5.
MTX
+ Biologic

30. Radiographic Progression
Early DMARD Intervention - BeST Trial Year 2 Outcomes
EULAR 2004 Final Show
Radiographic Progression
p = 0.003*
Sharp score progression was higher in groups 1 and 2 than in groups 3 and 4.
Reference:
Goekoop-Ruiterman YPM, De Vries-Bouwstra JK, Van Zeben D, et al. Treatment strategies in early rheumatoid arthritis: clinical and radiological outcomes after 2 year follow-up of the BeSt Study. Abstract L4 ACR 2004.
* Overall P-value, SDD = smallest detectable difference
Goekoop-Ruiterman YPM, et al. Abstract L4 ACR 2004.

31. BeSt Trial - Disposition of patients in the anti-TNF arm:
EULAR 2004 Final Show
120 enrolled
8 stopped for side effects
22 did not achieve response
13 continued
77 stopped because they achieved a DAS44 <2.4
46 were on 3mg/kg
22 on 6 mg/kg
6 on 7.5 mg/kg
3 on 10 mg/kg
Van der Bijl AE, et al. ACR 2005, Abstract 876.

33. Sustainability of response

34. TEMPO Trial Withdrawals: MTX, 30%; ENBREL, 24%; ENBREL + MTX, 16%
EULAR 2004 Final Show
TEMPO Trial
ENBREL (n=223)
MTX (n=228)
Randomized
(N=686)
ITT Population
(N=682)
Failure on 1 DMARD
No recent MTX
ACR-N
24 Weeks
Total Sharp Score
52 Weeks
Endpoints
Baseline
Enbrel® (etanercept) + MTX (n=231)
Key Point:
In the multicenter, double-blind TEMPO trial, patients who had failed at least one DMARD other than MTX were randomized to one of three treatment regimens.
A double-blind trial was conducted in 682 patients in 92 centers in Europe and Australia. After screening, 686 patients who had inadequate response to at least one DMARD were randomized to one of three treatment groups. Four randomized patients did not receive any study agent, so the ITT population was 682. Primary efficacy analysis was based on this population.1
Unlike previous anti-TNF trials, TEMPO compared three proven regimens to each other. The goal of this study was to compare the efficacies of the combination of Enbrel® (etanercept) and MTX versus MTX monotherapy and ENBREL monotherapy.1
This trial also differed in that all three treatment regimens were initiated at the start of the trial.1
Patients in this trial would be considered appropriate candidates for initiation of MTX therapy, rather than chronic MTX patients recalcitrant to therapy.1
Patients received either ENBREL 25 mg SC or placebo SC twice weekly, and either oral MTX or oral placebo once weekly, depending on the study group. MTX was initiated at 7.5 mg per week and could be increased over time up to 20 mg per week if the patient had an inadequate response. All patients received folic acid 5 mg twice weekly.1
For patients receiving MTX, escalation of MTX was required if a patient had any active joints. MTX could be decreased or suspended in the instance of adverse events or sustained elevation of liver enzymes. The mean dose after the escalation period was approximately 17 mg per week.1
Primary outcomes were the area under the curve (AUC) of the ACR numeric score (ACR-N) at 24 weeks and changes from baseline in total Sharp score at 52 weeks.1
A double-blind extension phase of this study continued beyond 52 weeks, with patients receiving the same treatment as before.1
Withdrawals for any reason were 30% in the MTX arm, 24% in the ENBREL arm, and 16% in the ENBREL + MTX arm.1
Reference: 1. Data on file, Wyeth Pharmaceuticals Inc., Philadelphia, Pa.
Withdrawals: MTX, 30%; ENBREL, 24%; ENBREL + MTX, 16%
Klareskog et al. Lancet 2004; 363:

35. TEMPO Trial - Year 3 Results ACR Response
EULAR 2004 Final Show
TEMPO Trial - Year 3 Results ACR Response
MTX (n=228) 90
86 † ‡
Etanercept (n=223) 80 75
Etanercept + MTX (n=231) 71
71 † ‡ 70 60
54*
Percent of Patients
49† ‡ 50 42 40 30 27
Patients receiving etanercept or MTX experienced a significant improvement as measured by ACR20, 50, and 70 at two years. In the combination group, 86% of patients experienced clinical improvement as defined by ACR20. In the same group, 71% of patients achieved an ACR50 response, and 49% achieved an ACR70 response. Etanercept + MTX demonstrated significantly higher ACR response rates in comparison with MTX alone.
For ACR50, the gap between the combination regimen and monotherapy widened as compared with the ACR20 results. The 71% response for the combination therapy was significantly greater than either the 54% response for etanercept monotherapy or the 42% response for MTX monotherapy.
A total of 49% of patients receiving etanercept + MTX achieved an ACR70 response. This is more than twice the response rate of patients receiving MTX alone.
References: 1. van der Heijde D, Klareskog L, Wajdula J, Pedersen R, Fatenejad S. Three Years of Sustained Halting of Radiographic Progression With Combination Etanercept and Methotrexate: Results from the TEMPO Trial. Abstract L16, ACR 2005.
2. Singh A, Klareskog L, Pedersen R, Fatenejad S. Results of Patient-Reported Outcome in a 3-Year Double Blind Study of Etanercept and Methotrexate, Alone and Combined, in Patients with Active Rheumatoid Arthritis. Abstract 551, ACR 2005. 21 20 10
ACR20
ACR50
ACR70
* p<0.05, etanercept vs. MTX
† p<0.05 combination vs. MTX
‡ p<0.05 combination vs. etanercept
van der Heijde D, et al. ACR 2005, Abstract L10.

36. TEMPO Trial - Year 3 Results DAS44 Remission
EULAR 2004 Final Show
TEMPO Trial - Year 3 Results DAS44 Remission †‡
At 3 years, clinical remissions, as defined by a DAS44 <1.6, were achieved by more than 40% of the group receiving etanercept + MTX. Concurrent initiation and use of etanercept + MTX advances the therapeutic objective of achieving clinical remission and repairing structural damage.
Approximately 22% and 18% of the etanercept monotherapy and MTX monotherapy arms, respectively, also achieved clinical remissions.
References: 1. van der Heijde D, Klareskog L, Wajdula J, Pedersen R, Fatenejad S. Three Years of Sustained Halting of Radiographic Progression With Combination Etanercept and Methotrexate: Results from the TEMPO Trial. Abstract L16, ACR 2005.
2. Singh A, Klareskog L, Pedersen R, Fatenejad S. Results of Patient-Reported Outcome in a 3-Year Double Blind Study of Etanercept and Methotrexate, Alone and Combined, in Patients with Active Rheumatoid Arthritis. Abstract 551, ACR 2005.
* p<0.05, E vs. MTX
† p<0.05, combination vs. MTX
‡ p<0.05, combination vs. E
van der Heijde D, et al. ACR 2005, Abstract L10.

37. What about Radiographic Progression ?

38. Primary Radiographic Endpoint: Change in TSS From Baseline - Year 3
EULAR 2004 Final Show
5.95 (CI 2.96, 8.94)
1.61* (CI 0.41, 2.81)
Combination and etanercept groups had significantly less progression of disease for all radiographic endpoints at year 2 than methotrexate group.
Combination of etanercept and MTX resulted in statistically significant lowering of total Sharp score and erosion score compared with baseline with a “negative” progression rate.
TEMPO is the first study suggesting that repair of structural damage may be induced in a group of patients with the combination of etanercept and methotrexate since the entire 95% CI for the combination group was below zero for TSS, as well as for JSN. [Confidence Intervals (2-sided 95% confidence intervals) Etanercept + MTX (-1.07, -0.78)].
References: 1. van der Heijde D, Klareskog L, Wajdula J, Pedersen R, Fatenejad S. Three Years of Sustained Halting of Radiographic Progression With Combination Etanercept and Methotrexate: Results from the TEMPO Trial. Abstract L16, ACR 2005.
2. Singh A, Klareskog L, Pedersen R, Fatenejad S. Results of Patient-Reported Outcome in a 3-Year Double Blind Study of Etanercept and Methotrexate, Alone and Combined, in Patients with Active Rheumatoid Arthritis. Abstract 551, ACR 2005.
* p < 0.05, Etanercept vs MTX
† p < 0.05, combination vs MTX
‡ p < 0.05, combination vs Etanercept
-0.14†‡ (CI –1.07, 0.78)
van der Heijde D, et al. ACR 2005, Abstract L10

39. No Radiographic Progression
Long-term Safety & Efficacy TEMPO Trial - Year 3 Results
EULAR 2004 Final Show
No Radiographic Progression
After 3 years, the percentage of patients who experienced ≤ 0.5 change in Total Sharp Score was 50.5% for the methotrexate group, 61.1% in the etanercept group and 76% in the combination group (p < 0.05, combination vs MTX, p < 0.05, combination vs. etanercept).
References: 1. van der Heijde D, Klareskog L, Wajdula J, Pedersen R, Fatenejad S. Three Years of Sustained Halting of Radiographic Progression With Combination Etanercept and Methotrexate: Results from the TEMPO Trial. Abstract L16, ACR 2005.
2. Singh A, Klareskog L, Pedersen R, Fatenejad S. Results of Patient-Reported Outcome in a 3-Year Double Blind Study of Etanercept and Methotrexate, Alone and Combined, in Patients with Active Rheumatoid Arthritis. Abstract 551, ACR 2005.
van der Heijde D, et al. ACR 2005, Abstract L10

40. EULAR 2004 Final Show
TEMPO trial - Disconnect between Disease Activity / Inflammation and Radiographic Progression (2 year data)
Patients were startified according to:
CRP levels: < 5 mg/L ; 5-15; > 15
DAS44:
<1.6 (remission) / (Low disease activity)
(moderate diseaseactivity)
>3.7 (high disease activity)
Results:
In the MTX group only the High CRP and High DAS progress
In the MTX + ETN no progresson regardless of CRP level and disease activity
Landewé R et al. ACR 2005, Abstract 867.

41. TEMPO trial - Disconnect between Disease Activity Radiographic Progression
EULAR 2004 Final Show
Change in Sharp Score by Treatment Group Stratified
For Subcategories of ta-CRP*
A statistically significant interaction between treatment and ta-CRP with respect to change in Sharp score was confirmed by GMLM (p<0.001). The figure shows that radiographic progression deviated from zero in the methotrexate-only group and somewhat in the etanercept-only group by increasing ta-CRP values, while it remained below zero in the methotrexate + etanercept group. Differences were not due to differences in absolute ta-CRP values between groups.
Reference:
Landewe R, et al. A disconnect between inflammation and radiographic progression in patients treated with etanercept plus methotrexate and etanercept alone compared with methotrexate alone: results from the TEMPO trial. ACR 2005 San Diego, Abstract 867
* Time-averaged CRP
Landewé R et al. Abstract 867, ACR 2005.

42. Disconnect Between Disease Activity and Radiographic Progression
EULAR 2004 Final Show
Change in Sharp Score by Treatment Group Stratified for Subcategories
of ta-DAS*
In the lowest ta-DAS category (compatible with the absence of inflammation) progression in the etanercept plus methotrexate group was at a significantly lower level compared with progression in the MTX group.
The mean progression rate was negative only in both etanercept groups but not in the methotrexate group, despite remission or very low disease activity. These observations suggest that etanercept and methotrexate may block very different pathways of joint damage.
This disconnect between inflammation and radiographic progression observed in this analysis confirms other work and points to a class-specific effect of the TNF antagonists.
The consistently negative mean progression rates across all subgroups of ta-CRP and ta-DAS in the etanercept plus methotrexate indicates a situation in which bone formation (eg., filling in of existent erosions) overweighs bone resorption.
The authors conclude that the results of this analysis suggest that therapy with etanercept and methotrexate should be continued even in patients in whom such a therapy has not resulted in complete suppression of symptoms and recommend further research to explore this hypothesis.
Reference:
Landewe R, et al. A disconnect between inflammation and radiographic progression in patients treated with etanercept plus methotrexate and etanercept alone compared with methotrexate alone: results from the TEMPO trial. ACR 2005, Abstract 867
* Time-averaged DAS
Landewé R et al. Abstract 867, ACR 2005.

43. EULAR 2004 Final Show
Conclusions
Halting of radiographic progression is achievable for many patients
DMARDs produce clinical remission but structural damage may progress, due to incomplete suppression of synovitis
TNF blockade (with MTX) can halt structural damage due to more complete suppression of synovitis, and ?direct osteoclast effect