1. Yusuf Yazıcı, MD NYU Hospital for Joint Diseases, New York
Remission In Rheumatoid Arthritis (RA): How Will The New Criteria Change Our Approach To RA Treatment?
Yusuf Yazıcı, MD
NYU Hospital for Joint Diseases, New York

2. Disclosures Abbott BMS Celgene Centocor Genentech Janssen Merck Pfizer
Roche
Takeda
UCB

3. Background Early, aggressive treatment Measurement tools
Treat to target
Routine monitoring

4. Why Do We Need to Measure?
102 patients with RA on conventional treatment, judged by their rheumatologist to be in remission
% Meeting remission criteria 54
DAS28 remission criteria
Mean score
2.53
% Remission, <2.6 56
% Low disease activity, 2.6–3.2 20
% Moderate disease activity, 3.2–5.1 23
% High disease activity, >5.1 1
Association between baseline findings and radiographic progression over 12 months
Baseline variable
No radiographic progression, n=73
Radiographic progression, n=17
Odds ratio (95% CI) P
RF + (n) 28 11
2.95 (0.98, 8.86)
0.054
ESR, median, mm/h 10 13
1.01 ( )
0.667
CRP, median, mg/L 5
1.01 (0.93, 1.10)
0.765
Met ACR remission (n) 41
0.33 (0.10, 1.02)
Met DAS28 remission (n) 44 6
0.36 (0.12, 1.08)
0.068
DAS28 score, mean
2.48
2.89
1.54 (0.89, 2.65)
0.122
Total US PD score, median 1
1.36 (1.02, 1.81)
0.038
Dominant hand US PD score, median
1.64 (1.03, 2.61)
0.036
Brown AK et al. Arthritis Rheum. 2008;58:

5. ACR Core Data Set Swollen joint count Tender joint count
Physician Global Assessment
ESR or CRP
Physical Function (HAQ, MHAQ, MDHAQ)
Pain
Patient Global Assessment
Radiographs

6. Clinical Measurement Tools
Outcome Measures in RA
ACR20
DAS28
SDAI
CDAI
GAS
ERAM
RADAI
RADARA
RAPID3
Patient function + + + +
Patient pain + + + +
Patient global + + + + + + +
MD global + + + +
# Tender joints + + + + + + +
Repeated studies, and now BeSt have shown that close supervision and monitoring of responses to drive treatment results in better patient outcome measures. However, very few physicians (12%) are obtaining and/or using these measures. Some of the reasons given include: they are too difficult to do outside of a clinical trial, they take too much time (although my poster shows that the method proposed by Ted Pincus takes 20 seconds---shameless plug--), or require labs and formulae that are not available or difficult to calculate. To make these calculations more user friendly, many have proposed alternatives to the ACR criteria or DAS28. Smolen has been using SDAI and now CDAI (which eliminates the CRP), Pincus is using the MD-HAQ and “RAPID” and now Dr. Cush has proposed another, simple measure that can be readily calculated by anyone, at the time of the office visit.
Global Arthritis Score: A Rapid Practice Tool for Rheumatoid Arthritis (RA) Assessment
PURPOSE: Validated outcome measures have been promoted to assess outcomes in RA clinical trials. However, such tools (ACR20, DAS, DAS28, HAQ-DI, MD-HAQ, SF-36, SDAI, mSDAI, etc) are seldom used in practice or clinical decision making. Reasons for their neglect include time constraints, uncommon measurements (global scores, long surveys), lab delays and complicated calculations. A recent survey of 1130 US rheumatologists revealed that only 12.2% used the HAQ and 6% calculated the disease activity score (DAS) when assessing RA. Half of US Rheums make treatment changes based on MD preferences, yet few use objective measures. This study will demonstrate the value and validity of a novel practice tool, the Global Arthritis Score (GAS), in the assessment and management of RA patients. The GAS is the sum of 3 measures: 1) patient pain (0-10 scale); 2) raw mHAQ (range 0-24; using the 8 question modified Health Assessment Questionnaire[HAQ]); and 3) tender joint count (0-28). GAS totals range from 0-62 and is easily acquired during the routine encounter. METHODS: 44 consecutive RA patients (and 181 clinic visits) form the data set used to compare and validate the GAS against the DAS28, DAS-CRP, simple disease activity index (SDAI), modified SDAI (without CRP), MD global, and swollen joint count (SJC). To be included patients had to have 2 or more visits with available data. All patients meet ACR criteria for RA diagnosis and included 7 men and 37 women with a mean age of 50 yrs and disease duration of 11.7 years. Early RA (< 3yr) comprised 25% of group. Prednisone was used in 39%; with a mean dose of 7 mg/d. Patients had an average of 2.5 prior DMARDs. Half took DMARDs and 27% took MTX at mean of 18.8 mg/wk. TNF inhibitors were used in 59% at some time. Fitness of GAS to measure both activity (variables correlated for all visits) and treatment response (change in variables over time) was assessed. RESULTS: Spearman-rank correlation coefficients from this data set showed highly significant correlations (P< ) between the GAS and other validated outcome measures when assessing disease activity. Responses over time also showed the GAS to be equal or superior to the DAS and other measures. CONCLUSIONS: These analyses demonstrate the construct validity of the Global Arthritis Score (GAS) as applied to patients in clinical practice. The GAS is rapidly acquired, incorporates simple patient measures (pain, mHAQ) and is completed and calculated at the end of the tender joint exam. The GAS can be used to assess current activity, response to therapy and as a target measure of remission or near remission (eg GAS <8).
# Swollen joints + + + + + +
ESR or CRP + + +
SDAI=Simplified Disease Activity Index; CDAI=Clinical Disease Activity Index; GAS=Global Arthritis Score, ERAM=Easy Rheumatoid Arthritis Measure; RADAI=Rheumatoid Arthritis Disease Activity Index; RADARA=Real-Time Assessment of Disease Activity in Rheumatoid Arthritis; RAPID=Routine Assessment of Patient Index Data.
Cush JJ. Presented at: 2005 ACR Annual Scientific Meeting. November 12-17, San Diego, CA. Abstract 1854; Sesin CA et al. Semin Arthritis Rheum. 2005;35: ; Makinen H et al. Clin Exp Rheumatol. 2006;24:22-28; Yazici Y. Bull NYU Hosp Jt Dis. 2007;65(suppl 1):25-28; Call S et al. Presented at : 2007 ACR Annual Scientific Meeting. Boston, MA. Abstract 425. Fransen J et al; Rheumatol. 2000;39: 6

7. New ACR/EULAR RA remission criteria
Developed by committee using data from clinical trials
Assessed ability of candidate measures to predict: damage (change 0 in vdH/S score) and function (change in HAQ 0; HAQ 0.5) over 2 ys
Best results obtained by 2 proposed definitions:
TJC and SJC and CRP and Pt Global all 1 OR
SDAI 3.3
[SDAI = TJC (28) + SJC (28) + Phys global (0–10 cm VAS) + Pt global (0–10 cm VAS) + CRP (mg/dL)
[2108] - Predictive Validity of the New Preliminary ACR/EULAR Definitions for Remission in Rheumatoid Arthritis. David T Felson, MD, MPH1,Josef S Smolen, MD2,George A Wells, MSc, PhD3,Bin Zhang, DSc4,Lilian HD van Tuyl, PhD5,Julia Funovits6,Maarten Boers, MD, PhD, MSc7,for the ACR/EULAR commission to redefine remission in rheumatoid arthritis. Background: With remission in rheumatoid arthritis (RA) an increasingly attainable goal, there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome in clinical trials. Methods: A committee constituted from members of the American College of Rheumatology, the European League Against Rheumatism and the Outcome Measures in Rheumatology (OMERACT) Initiative guided the process and reviewed prespecified analyses from clinical trials of patients with RA. A stringent definition was requested including at least joint counts and an acute phase reactant, but excluding duration of state. As part of the search for a remission definition, trial data were analyzed to examine the ability of candidate measures to predict later good x-ray and functional outcomes (defined as change ≤0 in van der Heijde/Sharp scores and Health Assessment Questionnaire (HAQ) change ≤0 and HAQ score consistently ≤0.5 both during the 2nd year of respective trials). Likelihood ratios compared the proportion of patients in remission having the good outcome to the proportion of patients not in remission having the good outcome. To rank candidate definitions of remission, the p value from the logistic regression chi square test were used. Candidate definitions of remission were downgraded when they led to values of core set measures which suggested disease activity incompatible with remission. Results: Patients in a state of remission by several of the Boolean candidate definitions, as well as by traditional SDAI (≤3.3) and CDAI (≤2.8) definitions had an increased likelihood of both x-ray and HAQ stability (see Table 1). However, reaching remission according to DAS28, both at the traditional (<2.6) and a more stringent cut point (<2.0), was associated only with the likelihood of HAQ stability but not x-ray stability. Additional definitions were tested, including definitions that incorporated pain or patient global at remission levels and other variations, and results were similar. Apart from the DAS28 result, the analyses did not help to distinguish between definitions. Conclusion: Based on these and other considerations, we propose that a patient be defined as in remission based on one of two definitions of remission: 1: When their scores on the following measures are all ≤1: tender joint count, swollen joint count, CRP (in mg/dL) and patient global assessment (0-10 scale), OR 2: when their score on the SDAI ≤3.3. These new definitions can be uniformly applied and widely used in RA clinical trials. We recommend that one of these be prespecified in each trial as an outcome and that the results of both be reported. These definitions are currently 'preliminary' and are pending approval from the ACR and EULAR boards. Acknowledgements: Some of the results were generated using clinical trial data provided by Abbott, Amgen, and Wyeth-Pfizer.
Felson DT, et al. Ann Rheum Dis 2011

8. New remission criteria
New remission criteria for RA
“more stringent than DAS28, CDAI or RAPID3 remission”
Little information regarding
Feasibility of use in routine clinical care
If it is better than RAPID3 remission
a very simple, patient friendly tool and easily implemented in everyday patient care.

11. Patient-Reported Outcomes: Placebo Response at 6 Months
TJC
SJC
Phys Global
Pain (VAS)
Pt Global
HAQ (mean)
ESR
CRP
HAQ DI
% Change from Baseline
Improvement
Physician-derived
Patient-derived
Laboratory
Strand V et al. Rheumatol. 2004;43:

12. TCZ in DMARD-IR RA (ROSE)
TCZ 8 mg/kg (n=412) vs PBO (n=207), 1° EP: ACR50 Week 24
62 patients, subset analysis for 1-week results
DAS28, CRP, pain, PGA improved at 1 week; not joints or MDGA
TCZ 8 mg/kg + DMARDs
PBO + DMARDs
Pt Pain VAS
MD Global VAS
P=0.007
P=0.001
P=0.005
DAS28
Pt Pain
PGA
MDGA
MDHAQ-PF
SJC
TJC
Reason for inclusion:
Only study to show patient measures are more responsive to change at 1 week than physician measures, “ patient knows he is better, physician has no clue”
Subgroup had 1 week evaluations,
Only study to show patients measures respond earlier than MD measures (TJC and SJC)
No new safety signals
[1808] - Efficacy and Safety of Tocilizumab in Patients with Moderate to Severe Active RA and a Previous Inadequate Response to DMARDs: The ROSE Study. Purpose: Early and aggressive treatment of RA has been associated with improved outcomes. The objective of the Rapid Onset and Systemic Efficacy (ROSE) study was to assess the efficacy of tocilizumab (TCZ) versus placebo in combination with DMARDs in reducing signs and symptoms during 24 weeks of treatment in patients with moderate to severe RA who have had inadequate clinical response to DMARDs. Methods: 619 patients were randomly assigned to TCZ 8 mg/kg + DMARDs (TCZ, n=412) or placebo + DMARDs (control, n=207). The primary efficacy end point was ACR50 response at week 24. Efficacy parameters were assessed every 4 weeks through week 24. Disease activity was also assessed at 1 week for a subset of 62 patients. Safety and laboratory parameters were assessed throughout the study. Results: Most patients were female (81%) and Caucasian (81%); mean age was 55 y, mean disease duration was 8.6 y, mean number of previous DMARDs was 1.2, and mean DAS28 was 6.5. At week 24, there was a significantly higher percentage of ACR50 responders (primary end point) in the TCZ group than in the control group (30.1% vs 11.2%; p<0.0001). Significantly higher percentages of patients in the TCZ group than in the control group achieved ACR20 and ACR50 responses from week 4 through week 24 and ACR70 responses from week 8 through week 24 (Table). Patients in the TCZ group had significant improvement in RAPID3 scores from week 4 through week 24 and in FACIT-Fatigue scores from week 8 through week 24 compared with control (Table). In the TCZ group, improvements in CRP and Hb levels occurred early (week 4) and were sustained through week 24; CRP improvement was significant at all time points (p<0.0001). In the subset, DAS28 and patients' pain and global assessment scores significantly improved, and CRP levels normalized 1 week after TCZ treatment (p≤0.01 vs control). SAE rates/100 PY (95% CI) were 24 (17, 33) and 19 (11, 31) for the TCZ and control groups, respectively. Serious infections were reported in 2.9% and 0.5% of patients in the TCZ and control groups, respectively. Malignancies were reported in 0.7% and 1.5% of patients in the TCZ and control groups, respectively. ALT shifts from normal at baseline to >3× ULN occurred in 3.2% of TCZ patients and in 1.1% of control patients. Clinically significant (grade 3/4) decreases in neutrophil counts were reported in 2.9%/0% of TCZ patients; no grade 3/4 decreases were reported in control patients. There were no occurrences of decreased platelet counts to clinically significant values (grade 3/4). Conclusions: TCZ led to significant improvements in disease activity, ACR responses, and CRP and Hb levels as early as week 4 and in DAS28 response as early as week 1; responses persisted through week 24. Safety findings were consistent with the known safety profile of TCZ. With early and sustained efficacy, TCZ is an effective treatment option for patients with RA who have failed DMARDs.
(P=0.0502)
P=0.007
P=0.01
P=0.005 NS NS NS
Patient, not physician, measures show improvement at 1 week
Yazici Y, et al. ACR 2010, Atlanta, #1808

13. CATCH: Remission prevalence in early RA new criteria vs other criteria
RF/ CCP (+)
Bio %
CRP
DAS28<2.8
56/62 7
0.33
DAS28<2.0
55/61
0.26
SDAI<3.3
59/64 9
0.32
CDAI<2.8
58/64 10
0.38
ACR/ EULAR
54/65 8
0.27
% pts in REM based on: DAS28 <2.6, DAS28<2.0, CDAI <2.8, SDAI <3.3, ACR/EULAR ≤4 at 1 y
Kappa-statistics of agreement between criteria were performed
CATCH= Canadian Early Arthritis Cohort
Components: TJC, SJC, CRP, (PtVAS), (MDVAS) & % receiving biologics
Of 689 pts, 71% & 91% met 1987 & 2010 ACR criteria
B. Kuriya 1, Y. Sun 1, G. Boire 2, B. Haraoui 3, C. Hitchon 4, J. Pope 5, C. Thorne 6, D. Ferland 7, E. Keystone 1, V. Bykerk 8,* and CATCH
PREVALENCE OF REMISSION IN EARLY RA – A COMPARISON OF NEW REMISSION CRITERIA TO ESTABLISHED CRITERIA
SAT0405
Background: New RA remission (REM) criteria were recently proposed by ACR/EULAR (1).
1U of Toronto, Toronto, 2U Sherbrooke, Sherbrooke, 3Institut de Rhumatologie, Montreal, 4U Manitoba, Winnipeg, 5U Western Ontario, London, 6Southlake Regional Health Ctr, Newmarket, 7Hopital Maisonneuve Rosement, Montreal, Canada, 8BRIGHAM & WOMEN'S HOSPITAL, Boston, United States
Methods: The proportion of patients (pts) in REM based on a DAS28 <2.6, DAS28 <2.0, CDAI <2.8, SDAI <3.3 and ACR/EULAR ≤ 4 were calculated at 1 year. Tender/swollen joint count (TJC) (SJC), CRP, patient and physician global assessment of disease on visual analog scale [(Pt-VAS), (MD-VAS)] and % of pts receiving biologics were calculated. Kappa-statistics of agreement between criteria were performed.
Objectives: To evaluate the prevalence of REM and agreement between various REM definitions in the Canadian Early ArThritis CoHort (CATCH).
Results: Of 689 eligible pts 71% and 91% of pts met 1987 and 2010 ACR criteria for RA; mean (SD) age was 53.5 (13.4) years, symptom duration was 6.2 (3.5) months, 75% were female, 58% were anti-CCP+ and 63% RF+. Characteristics of pts by REM group and core components for each criterion are shown (Table). The ACR/EULAR criteria had substantial agreement with SDAI (k= 0.77) and CDAI (k=0.75). Agreement was fair with DAS28<2.6 (k=0.40) and DAS28<2.0 (k=0.40). 
Table: Comparison of characteristics and core components of remission definitions 
SDAI<3.3
DAS28<2.0
DAS 28<2.6
Patient Characteristics
ACR/EULAR
CDAI<2.8     
260 (47)
Number in REM (%)
144 (27)
133 (28)
162 (29)
Age* years
124 (20)
50.2 (15.4)
49.6 (14.6)
50.1 (15.1)
50.6 (15.5)
50.1 (14.9) 70 71
Female (%) 77 76
55/61
56/62
RF/CCP positive (%)
59/64
Biologic use (%)
54/65
58/64 7 10 9
Core Components 8
0.6 (1.2)
TJC (28)*
0.4 (1.0)
0.1 (0.4)
0.2 (0.4)
0.4 (0.9)
0.7 (1.5)
SJC (28)*
0.1 (0.3)
0.33 (0.44)
CRP* mg/dl
0.38 (0.46)
0.32 (0.37)
0.26 (0.33)
1.4 (1.7)
Pt-VAS*
0.27 (0.24)
0.6 (0.7)
1.2 (1.6)
MD-VAS*
0.3 (0.4)
0.5 (0.7)
0.3 (0.5)
0.5 (1.0)
0.8 (1.2)
* mean (SD)
0.3 (0.6)
Conclusions: The prevalence of clinical REM ranged between 20 and 47%. Achievement of REM was lowest using the ACR/EULAR criteria and these perform similarly to the SDAI and CDAI.  In contrast, there was poor agreement between these criteria and frequently used DAS-based definitions. Higher pt-VAS appears to account for most of the variability between the proportions achieving REM in each group.
References: (1) Felson et al. Predictive validity of the new preliminary ACR/EULAR definitions for remission in rheumatoid arthritis. ACR 2010.
Disclosure of Interest: B. Kuriya: None Declared, Y. Sun: None Declared, G. Boire: None Declared, B. Haraoui: None Declared, C. Hitchon: None Declared, J. Pope: None Declared, C. Thorne: None Declared, D. Ferland: None Declared, E. Keystone: None Declared, V. Bykerk Grant / Research support from: Amgen, Pfizer, Abbott, UCB, Roche
ACR-EULAR criteria agrees w/ SDAI (k=0.77) & CDAI (k=0.75)
Fair agreement w/ DAS28<2.6 (k=0.40) & DAS28<2.0 (k=0.40)
All remission is not the same1,2
1. Kuriya B, et al. EULAR 2011, London, #SAT0405; 2. Bernard M, et al. Ibid, #OP0027

14. Utility of 2011 ACR/EULAR 2011 remission criteria
US VA and community practice cohort study1
1341 VA patients / 9700 visits (91% men)
1168 community practice patients / 6362 visits (28% men)
Remission:
Cross sectional: 8.9% / 8.3%
Cumulative: 24.4% / 19.0% over 2.2 y
1.9–4.6% patients met remission at ≥ 2 visits
Among all patients, <3% had remission lasting 2 y
DREAM: ↑ PtG most common reason for failure to meet remission2
Non-inclusion of feet may overestimate remission3
Patients in ACR/EULAR remission have function capacity = to normal4
FRI0333
REMISSION OF RHEUMATOID ARTHRITIS IN CLINICAL PRACTICE: APPLICATION OF THE ACR/EULAR 2011 REMISSION CRITERIA
K. Michaud 1, 2,*, S. Shahouri 3, T. R. Mikuls 4, L. Caplan 5, J. Anderson 3, R. Busch 3, T. Shaver 3, S. Wang 3, D. Weidensaul 3, F. Wolfe 1
1National Data Bank for Rheumatic Diseases, Wichita, 2University of Nebraska Medical Center, Omaha, 3Arthritis and Rheumatology Clinics of Kansas, Wichita, 4Omaha Veterans Affairs Medical Center, Omaha, 5Denver Veterans Affairs Medical Center, Denver, United States
Background: Remission is the most desirable outcome of rheumatoid arthritis (RA). Recently the ACR/EULAR (AE) described new remission criteria for use in clinical trials clinical trials, but also proposed remission criteria for clinical practice. However, there is little information about the performance of the new criteria in practice, and the rate and durability for the new remission is not known.
Objectives: To describe cross-sectional and cumulative proportion ever achieving remission in clinical practice, as well as remission durability and reliability of measurements, according to the various remission definitions.
Methods: We examined remission in the US Veterans Affairs RA (VARA) registry of 1,341 patients (91% men) with 9,700 visits and a community rheumatology practice (ARCK) of 1,168 patients (28% men) with 6,362 visits. We examined various remission criteria using the proposed Boolean definitions and the CDAI and SDAI methods proposed by AE. Analyses used all patient visits in multi-level models to determine cross-sectional and cumulative probabilities, as well as aspects of reliability of criteria components, such as joint counts and patients and physician globals.
Results: By AE definition for community practice (swollen and tender joints ≤1, patient global ≤1), cross-sectional remission was 8.3% (7.1, 9.5) for ARCK and 8.9% (7.9, 9.9) for VARA. Cumulative remission was 19.0% for ARCK and 24.4% for VARA over a mean of 2.2 years. Addition of ESR or CRP to criteria reduced cross-sectional remission to %, and use of CDAI/SDAI increased proportions to % % of patients met remission criteria at ≥2 visits.  Agreement between criteria definitions was good by Kappa and Jaccard measures, but not as good at patient level for clinical care. Remission was not persistent. Among patients in remission, the probability of a remission lasting 2 years was %.  Among all patients the probability of having a remission lasting 2 years was <3%. The various criteria and the criteria components (swollen and tender joints counts and physician globals) varied substantially among physicians as determined by median odds ratios in multilevel analyses.
Conclusions: Cross-sectional remission occurs at 4.6% to 10.1%, with cumulative probabilities 2-3 times greater. Long-term remissions are rare (<3%). Problems with reliability and agreement limit criteria usefulness in the individual patient.  However, the criteria can be an effective method for measuring clinical status and treatment effect in groups of patients in the community.
References: Felson et al. American College of Rheumatology/European League against Rheumatism: Preliminary Definition of Remission in Rheumatoid Arthritis for Clinical Trials. In Press.
Disclosure of Interest: None Declared
Remission is uncommon in the clinic, especially long term
1. Michaud K, et al. EULAR 2011, London, #FRI0333; 2. Vermeer M, et al. Ibid, #OP0311; 3. Bakker MF, et al. Ibid, #SAT0376; 4. Listing J, et al. Ibid, #THU0351

15. HAQ improvement and time in remission in RA patients using various criteria
BRASS Registry: pts with >2 y F/U; more time in remission  better HAQ
mdHAQ
–0.1
–0.05
–0.25
–0.15
–0.2 1 2 3 4
No. of yearly visits in remission
DAS28 <2.6
DAS28 <2.3
SDAI
CDAI
ACR/EULAR
 with respect to F/U visits
No. of yearly visits in remission
0.2
–0.2
–0.6
–0.4 1 2 3 4 4
4–11
11–22
>22
mdHAQ
 mdHAQ according to dd by DAS28-CRP <2.6 rem dd
The Relationship Between Time in Remission and Functional Status in Rheumatoid Arthritis
 Femke H.M. Prince1, Presentation Number: 333
 Background/Purpose:
It is presumed that patients with rheumatoid arthritis (RA) in sustained remission have a more favorable outcome. Our objective was to describe change in functional outcome in relation to the number of annual examination in remission in RA patients.
Method:
We analyzed annually collected disease activity variables and outcomes from a prospective, observational, single-center RA cohort, including participants with at least two years follow-up (n=871). Remission was determined by the DAS28-CRP4<2.6, SDAI<=3.3 and 2010 ACR/EULAR criteria. The outcome of functional status was measured using the multidimensional HAQ (mdHAQ) and data were analyzed using linear mixed models. For a secondary analysis we examined the relationship between remission and the minimal clinical important improvement (MCII) inmdHAQ (set at -0.3). In the secondary analysis, subjects with mdHAQ<0.5 at baseline were excluded since improvement is unlikely. 
Result:
Subjects in remission at one or more annual examinations, regardless of the remission criteria, had a more favorable outcome of mdHAQ compared to subjects who never reached remission (p<0.001). In addition, more time points in remission produced more favorable outcomes (see Figure). After 4 years of follow-up, more subjects (72%) with >60% of time in DAS28 remission reached the MCII compared to subjects with <60% (p=0.03) or no examinations in remission (p<0.001). When stratifying according to baseline mdHAQ, subjects with a low mdHAQ (0-0.5) at baseline remained at approximately the same level when in DAS28 remission (mean change mdHAQ= ), while subjects with a high mdHAQ ( ) at baseline showed improvement in functional status during DAS28 remission (mean change mdHAQ= , p<0.001) after 4 years.
Conclusion:
In our study, subjects with more annual examinations in remission experienced greater improvement in mdHAQ. During sustained remission, subjects with high baseline mdHAQ scores improved more than those with lower baseline mdHAQ.  
Figure; Change in mdHAQ score in relation to the number of time points in remission. For instance, for patients in DAS28 remission at 4 time points mdHAQ improved with 0.21 per year compared with the improvement of 0.14 per year of patients with only 1 time point in DAS28 remission.
Duration of time in remission regardless of measure correlates with HAQ improvement; patients with early RA do better
Prince FHM, et al. ACR 2011, Chicago, #333

16. Impact of different remission criteria on functional ability
5788 RA pts from NOR-DMARD registry: starting DMARDs (n=3875) or biologics (n=1913)
DAS28
CDAI
RAPID3
ACR/EULAR
% remission, 3 mo
19.1
8.1
17.0
9.3
% no Δ mHAQ, 3–12 mo
65.7
64.9
65.2
63.6
% remission, 6 mo
24.7
11.3
19.8
12.3
69.6
73.6
69.8
72.6
Different Remission Definitions Capture Different Proportions of patients with Rheumatoid Arthritis Treated in Clinical Practice
Till Uhlig1, Presentation Number: 1229
Background/Purpose:
Clinical remission is the treatment target in rheumatoid arthritis (RA) and several composite indices are available for evaluation of remission states, including the newly formulated ACR/EULAR definition. These definitions have not been applied in real life daily clinical practice.
The purpose of this study was to examine how often clinical remission is achieved in clinical practice using existing definitions, and to test how well patients in remission preserve physical function.
Method:
Data for this study were provided by the NOR-DMARD register in all 5788 patients with RA started with a synthetic (n=3875) or biological DMARD (n=1913). Age was mean (SD) 55.3 (29.9) y, disease duration was 8.2 (9.6) y, 73.3% of patients were females.
Applied definitions for clinical remission included the Disease Activity Score based on 28 joint counts (DAS28) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, the Clinical Disease Activity Index (CDAI) ≤2.8, Routine Assessment of Patient Index Data (RAPID3, range 0-10) ≤1, and the preliminary ACR/EULAR remission definition where in the Boolean (BOOL) application tender joint count, swollen joint count, patient global assessment (scale 0-10), and CRP (mg/dL) all must be ≤1. ACR/EULAR remission is warranted if either ACR/EULAR BOOL is satisfied or SDAI ≤3.3. We also explored a practical definition of ACR/EULAR BOOL without CRP (ACR/EULAR PRAC). Data after 3 and 6 months of treatment were used for assessment of remission. Then patients with remission at 3 months were examined for deterioration of physical function (measured by the modified Health Assessment Questionnaire [MHAQ]) between months 3 and 12, likewise remission at month 6 for deterioration between months 6 and 12. Result: The table shows percentages of patients in remission after 3 months and 6 months, and further among these patients with remission at 3 and 6 months percentages of patients with no deterioration in MHAQ until 12 months. SDAI, CDAI and the new ACR/EULAR definition for remission are most stringent and classify 7-8% as in remission after 3 months of DMARD treatment, and 9-11% after 6 months. DAS28 and RAPID3 classify most patients as in remission. All remission definitions performed similar in identifying patients with preserved physical function.
Conclusion: Definitions of remission differ regarding the proportion of patients classified as in remission after 3 and 6 months of DMARD treatment in clinical practice. However, no individual definition seems superior in identifying patients who preserve physical function until 12 months.
Different numbers of patients achieve remission, but no difference in predicting physical function
Uhlig T, et al. ACR 2011, Chicago, #1229

17.
BRASS: Radiological progression in remission by new ACR/EULAR criteria vs other criteria
BRASS: single-centre prospective observational cohort. LR: likelihood ratio
535 pts (442 female): 359 CCP+, 205 biologic use, 339 RF+. BL Dz activity & X-ray at BL; X-ray and change ≥ 1 unit/y in TSS at 2 y. Mean age: 57.6 y; Dz dur: 14.2 y
SAT0398: RADIOLOGICAL PROGRESSION IN REMISSION BY THE NEW ACR/EULAR CRITERIA FOR REMISSION: A COMPARISON TO OTHER ESTABLISHED REMISSION CRITERIA
S. Lillegraven 1, 2,*, F. H. Prince 1, V. P. Bykerk 1, N. A. Shadick 1, B. Lu 1, M. L. Frits 1, C. K. Iannaccone 1, E. A. Haavardsholm 2, T. K. Kvien 2, M. E. Weinblatt 1, D. H. Solomon 1
1Division of Rheumatology, Brigham and Women's Hospital, Boston, United States, 2Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
Background: New RA remission criteria were proposed by EULAR and ACR in 2010, aiming to identify patients with good functional and radiological outcomes.
Objectives: The objective of this study was to compare the subsequent rate of erosion progression among RA patients assessed to be in remission by common remission criteria, focusing on the performance of the new ACR/EULAR criteria.
Methods: 535 RA patients from BRASS, a single-centre prospective observational cohort, were included in the study. Disease activity was assessed at baseline, and X-rays at baseline and 2 years. The patients were treated according to clinical practice. X-rays were scored (Sharp method) by trained readers. A change of ≥ 1 unit/year in the total Sharp score was classified as progression. Remission threshold for DAS28 (calculated with CRP and 4 variables) was 2.6, SDAI 3.3, and CDAI 2.8. ACR/EULAR criteria require all of the following to be ≤ 1: CRP in mg/dL, tender / swollen joints and patient global assessment (latter on a 0-10 scale). Patients were grouped according to remission status at baseline. Mean (SD) and median progression in Sharp score over two years and positive likelihood ratios for absence of progression were calculated for each remission criteria.
Results: The mean (SD) age for all 535 patients was 57.6 (12.7) years, disease duration was 14.2 (12.3) years, 442 (82.6%) were female, 359 (67%) were anti-CCP positive, 205 (38%) were on biologic therapy, and 339 (63%) were rheumatoid factor positive. The number of patients in remission at baseline was 106 (20%) for DAS28, 37 (7%) for SDAI, 26 (5%) for CDAI, and 30 (6%) for EULAR-ACR criteria. The percentages of biologic treatment among patients in remission ranged from 43% (DAS28) to 57% (SDAI). The mean (SD) annual change in Sharp score was 0.93 (2.9) for DAS28, 0.65 (2.4) for SDAI, 0.37(1.5) for CDAI and 1.08 (3.9) for ACR/EULAR criteria, although this was influenced by the distribution of the patients (see Figure). The median change in Sharp score was 0 for all groups. 30% (DAS28), 24% (SDAI), 19% (CDAI) and 20% (ACR/EULAR) were classified as progressors. The LR+ for good outcome (lack of radiological progression) was 1.5 for DAS28, 2.1 for SDAI, 2.8 for CDAI and 2.6 for ACR/EULAR criteria. The figure shows a cumulative probability plot for patients fulfilling the different remission criteria at baseline.
Conclusions: In this observational cohort, the new ACR/EULAR criteria performed similarly to established remission criteria with regards to subsequent 2-year change in Sharp score.

18. NYU Arthritis Registry Monitoring Database (NYU ARMD)
Established in 2005
All consecutive patients
~800 RA patients,
~6500 all dx patients
MDHAQ completed at each and every visit by all patients as part of routine care and part of the medical record
“if there is a reason to visit the doctor, there is a reason to complete a questionnaire”
Ted Pincus, MD

19. MDHAQ page 1

20. MDHAQ page 2

21. RAPID3 (Routine Assessment of Patient Index Data 3)

22. RAPID3 (Routine Assessment of Patient Index Data 3)
MDHAQ functional score(0-10)
Pain VAS (0-10)
Patient Global Assessment VAS (0-10)
RAPID4 and RAPID5
RADAI - Patient Reported Joint Count (0-10)
Physician Global Assessment (0-10) 22

23. DAS28 and RAPID3 RA Categories
DAS28 Categories
<2.6 = Remission
= Low DAS
= Moderate DAS
>5.1 = High DAS
RAPID3 Categories
< 3.0 = Near Remission
= Low Severity
= Moderate Severity
>12.0 = High Severity

24. RAPID3 vs DAS28 in 285 RA Patients
Reference
1. Pincus T, Sokka T. Rheum Dis Clin of North Am. 2004;30:725–751.
Spearman
correlation
rho = 0.657
Pincus T, et al. J Rheumatol. 2008;35:

25. RAPID3 & DAS28 Categories are Correlated Significantly in 285 Patients at 3 Sites
RAPID3 Scores
> 6.1 = High or moderate severity
< 6.0 = Low severity or remission
Total
> 3.2 = Moderate or high activity
114 (81%)
26 (19%)
140 (49%)
< 2.6 = Low activity or remission
47 (32%)
98 (68%)
145 (51%)
161 (56%)
124 (44%)
285
Pincus T, et al. J Rheumatol. 2010

26. Time Needed to Score Various RA Measures
Yazici Y, et al. J Rheumatol. 2008;35:603.

27. Methods NYU Arthritis Registry Monitoring Database (ARMD)
Prospective, consecutive patient data since 2005
all patients seen in routine care
Each patient with any diagnosis completes a 2-sided, 1-page MDHAQ at every visit as part of routine clinical care
MDHAQ includes scales for
physical function
pain
patient global estimate
fatigue
self-report RADAI painful joint count
Last visits of RA patients seen between July 2005 and April 2011 were studied.
Differences in self-report MDHAQ scores, RAPID3 and the new ACR remission criteria were analyzed

28. RAPID3 Disease State at Last Visit

29. NYU ARMD Registry

30. Results
704 RA patients (mean age 53.9, disease duration 5.5 years, 80% female)
16% (116) were in remission as defined by RAPID3
9% low, 27% moderate, and 48% were high disease activity
17% (118) were in remission by the new ACR/EULAR criteria
Percent agreement between remission by RAPID3 and new ACR criteria was 96%
with a very strong agreement beyond chance (kappa = 0.86, p < 0.001).

31. ACR Core Dataset by RAPID3 Remission
Active
Total N
113
565
678
Age (Years)
53.3 (15.1)
54.8 (15.3)
54.6 (15.3)
Duration (Years)
5.1 (6.4)
5.5 (6.9)
5.4 (6.8)
Female (%)
91 (81.3%)
466 (84.6%)
557 (84.0%)
Function [0-10]
0.8 (0.6)
3.4 (2.1)
3.2 (2.1)
Pain [0-10]
1.0 (0.5)
5.7 (2.7)
5.2 (2.9)
Global [0-10]
1.0 (0.6)
5.4 (2.6)
5.1 (2.7)
MD Global [0-10]
1.5 (1.0)
2.6 (1.5)
2.5 (1.5)
Swollen [0-28]
0.1 (0.3)
2.0 (3.4)
1.6 (3.1)
Tender [0-28]
0.6 (1.9)
4.0 (4.4)
3.4 (4.3)
ESR (mm/hr)
19.3 (17.4)
28.1 (24.2)
26.0 (23.0)

32. RAPID3 components

33. ACR Core Dataset by Remission
Remission Criteria
RAPID3
ACR/EULAR
Age (Years)
52.7 (15.6)
56.1 (8.1)
Duration (Years)
4.8 (6.2)
3.9 (2.6)
Function [0-10]
0.3 (0.5)
0.5 (0.6)
Pain [0-10]
0.6 (0.6)
Global [0-10]
0.4 (0.6)
0.3 (0.4)
MD Global [0-10]
1.0 (1.1)
Swollen [0-28]
0.1 (0.4)
0.2 (0.4)
Tender [0-28]
0.7 (2.0)
ESR (mm/hr)
17.5 (15.6)
22.0 (16.1)
CRP (mg/dL)
2.4 (4.5)
0.3 (0.2)

34. Conclusion
RAPID3 definition of remission performs similarly to the new ACR remission criteria and can likely be used in routine care with similar benefits as part of treat to target strategy
The ease of use of RAPID3 compared to the new criteria may make it a good option for busy clinics and clinicians
More important to use an outcome measure and target remission/low disease activity accordingly