The document discusses definitions of remission for rheumatoid arthritis (RA) and the goals of treating RA. It provides context on the history of RA treatment goals moving from symptom relief to preventing joint damage and achieving remission. The key points are: 1) Definitions of remission have evolved from the original ACR criteria to the 2011 ACR-EULAR definition, which includes boolean and index-based definitions for use in clinical trials. 2) Achieving early remission through aggressive treatment is associated with better long-term outcomes for RA patients. 3) The 2011 definition was developed for clinical trials but needs validation for use in practice to guide treatment and measure remission.

2. What's the meaning of remission?
Remission
)med dictionary): an abatement or lessening of the
manifestations of a disease
)Wiki): the state of absence of disease activity
in patients with a chronic illness, with the possibility of return
of disease activity.
a drug-induced state of remission : this is a second distinction is when
patients are continuing treatment during the so-called remission.

3. History of RA Treatment Goals
1(The first goal was clear: make Rheumatoid Arthritis
patients feel better.
2(Disability was generally treated with surgery.
3(Increasingly, however, the goal of treatment for RA
has become toward joint damage.
4(More recently, “clinical remission” has become a
typical goal of RA treatment.

4. Why we are looking for remission?
Remission as a concept has become increasingly
important as it has moved to top of agenda
Achieving remission early is associated with better
outcome
The speed of reaching remission correlates with long
term benefits

5. recommendation
The primary goal of treating the patient with rheumatoid arthritis is
to maximize long term health related quality of life through
control of symptoms , prevention of structural damage ,
normalization of function and social participation.
Clinical remission is defined as an absence of signs and
symptoms of significant inflammatory disease activity
Measure of disease activity must be obtained and documented
regularly as frequent as monthly for patients with moderate to
high disease activity.
The target of treatment of rheumatoid arthritis is to reach early
remission

6. Can early and aggressive treatment increase
the rate of (drug-induced) remission in RA?
The most effective treatment strategies at present are most likely the
combination of TNF inhibitors with other DMARDs. For the
combination of etanercept with methotrexate, a remission rate of 41%
)DAS remission( has been reported at the 2-year time point.
In addition, in the BeSt study, treatment with infliximab and methotrexate
combined with a tight control of treatment efficacy resulted in a DAS
remission in 56% of patients after 13 months of treatment; these
patients continued with methotrexate monotherapy without the need
to restart infliximab in the subsequent months.
The use of adalimumab together with methotrexate induced a remission
rate )DAS28( of 49% after 2 years of treatment

7. Current Definitions:
American college of Rheumatology ( ACR)
(ARA(
or more5
for at least 2 consecutive months:
-Morning stiffness not exceeding 15 minutes
-No fatigue
-No joint pain (by history(
-No joint tenderness or pain on motion
-No soft tissue swelling in joints
or tendon sheaths
-ESR < 30 mm/h (f(; < 20 mm/h (m(

8. Problems with ACR Definition
-Depends on measures not widely assessed now in RA
trials as:
Morning stiffness
(absent in many patients with active RA(
And Tendon sheath swelling
-Very strict definition
-Attainment very rare in RA trials
Thus unrealistic target for treatment success

9. It has been argued that the ACR criteria for remission are
difficult to apply for clinical trials, as patients do not easily
fulfill these criteria due to the time requirement of two
months and the inclusion of fatigue.
The ACR criteria contain a time constraint that results in a
lower percentage of remissions in comparison with the
assessment of remission at one time point. Obviously, a
time constraint in the definition of remission leads to less
'false-positive' findings of remission in patient
management.

10. Why is a new remission definition
rheumatoid arthritis needed?
-Increasing numbers of patients reach remission
-Abundance of remission definitions
‘strict’ definitions:ACR
-No definition universally used
-Variability in how each definition is operationalized
Need for a uniform definition

11. ACR/EULAR 2011 Provisional
Definition of Rheumatoid
Arthritis Remission:

12. The 2011 ACR/EULAR Definitions of
Remission in Rheumatoid Arthritis
Clinical Trials
BOOLEAN-BASED DEFINITION:
At any time point, patient must satisfy all of the following:
Tender joint count ≤1
Swollen joint count ≤1
C-reactive protein ≤1 mg/dl
Patient global assessment ≤1 (on a 0–10 scale(
INDEX-BASED DEFINITION
DAS28, SDAI
disease activity scoring system < 2.6
Simplified Disease Activity Index scoring < 3.3

13. Indexes Tested
DAS28
=0.56*√)TJC28) + 0.28*√(SJC28)
+ 0.36*Ln(CRP*10 + 1) + 0.014*PtGA (0-100 scale)
+ 0.96
Levels tested: DAS28 < 2.6
SDAI (Simplified Disease Activity Index(
=TJC28 + SJC28 + PtGA (0-10 scale) + PhGA (0-10) + CRP
(mg/dL(
Level tested: SDAI < 3.3

14. Global Assessment:
How to Word the Question
The following wording and response categories
should be used for global assessment:
Considering all of the ways your arthritis has
affected you,
how do you feel your arthritis is today?
Verbal anchors for the response are
‘very well’ and ‘very poor

15. Remission definition DMARD
monotherapy
(n=380)
Biological
monotherapy
(n=520)
Combination
Therapy
(n=330)
Total
(n=1230)
TJC,SJC,CRP < 1
+ PtGA < 1 9 7 22 12
+ PtGA, pain < 1 8 6 20 12
+ PtGA, PhGA < 1 8 7 20 10
+ PhGA, pain < 1 8 6 20 10
+ PtGA, PhGA,pain < 1 7 6 18 9
DAS28 <2.6 19 17 35 21
DAS28 < 2.0 5 8 24 10
SDAI ≤ 3.3 10 8 26 14
Percentage Achieving Remission in
Recent Trials by Definition

16. Concern 1:
28 Joints Used to Define Remission
vs. Full Joint Count
28 joints
counted
What if foot/ankle joints active? Should patient be in
remission?

17. In Patients with 28 Joint Count ≤ 1
>10%had active ankles/feet
In these, PtGA was often high, thus:
would not meet criteria for remission anyway
How many not in remission when full joint counts used (i.e.,
‘false positive’ for remission(?
Compare drop in % remission in 2 trials:
Trial 1: from 6% (28 count) 4% (full count(
Trial 2: from 14% 9%
1-4%less when only in 28 joints count remission

18. Recommendation for Joint Count
The new ACR/EULAR criteria do not require
inclusion of ankles and forefeet in the
assessment of remission but recommend that
these joints are also included in the
examination.

19. What value of ESR corresponds to CRP =
1?
In men with RA, CRP value of 1mg/dl corresponds roughly
to 20mm/hour*
In women with RA, CRP value of 1mg/dl corresponds
roughly to 30mm/hour*

20. Conclusion about Defining
Remission in Practice
Remission predicts the best clinical, functional
and structural outcomes
ACR/EULAR definitions of remission
were developed using trial data
and need to be validated for use in practice
settings

21. ACR-EULAR 2011 Definition of
Remission
For clinical trials
Boolean
SJC, TJS, PtGA, CRP all ≤1
Index-based
SDAI
)SJC+TJC+PhGA+PtGA+ CRP(
SDAI ≤3.3
DAS28
DAS28 < 2.6