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
Disclosures
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Abbott
BMS
Celgene
Centocor
Genentech
Janssen
Merck
Pfizer
Roche
Takeda
UCB
Background
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Early, aggressive treatment
Measurement tools
Treat to target
Routine monitoring
Why Do We Need to Measure?
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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 (0.96. 1.06)
0.667
CRP, median, mg/L
5
0
1.01 (0.93, 1.10)
0.765
Met ACR remission (n)
41
5
0.33 (0.10, 1.02)
0.054
Met DAS28 remission (n)
44
6
0.36 (0.12, 1.08)
0.068
2.48
2.89
1.54 (0.89, 2.65)
0.122
Total US PD score, median
1
1
1.36 (1.02, 1.81)
0.038
Dominant hand US PD score, median
0
0
1.64 (1.03, 2.61)
0.036
DAS28 score, mean
Brown AK et al. Arthritis Rheum. 2008;58:2958-2967.
ACR Core Data Set
1. Swollen joint count
2. Tender joint count
3. Physician Global Assessment
4. ESR or CRP
5. Physical Function (HAQ, MHAQ, MDHAQ)
6. Pain
7. Patient Global Assessment
8. Radiographs
Clinical Measurement Tools
Outcome Measures in RA
ACR20
DAS28
SDAI
CDAI
GAS
Patient function
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+
Patient pain
+
+
Patient global
+
MD global
+
# Tender joints
+
# Swollen joints
ESR or CRP
+
ERAM
RADAI
RADARA
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RAPID3
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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, 2005. San Diego, CA. Abstract 1854; Sesin CA et al. Semin Arthritis Rheum. 2005;35:185-196;
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;39:321-327.
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)
Felson DT, et al. Ann Rheum Dis 2011
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.
Patient-Reported Outcomes:
Placebo Response at 6 Months
25
21.4
20.3
% Change from Baseline
Improvement
20
15
11.7
11.6
10
Pain
(VAS)
5
HAQ
(mean)
HAQ
DI
ESR
CRP
0
-5
SJC
TJC
Phys
Pt
Global Global
-2.4
-2.8
-10
-9.3
-15
-20
-20.4
-25
Physician-derived
Strand V et al. Rheumatol. 2004;43:640-647.
Patient-derived
-21.5
Laboratory
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
Mean change from BL
TCZ 8 mg/kg + DMARDs
2
0
-2
-4
-6
-8
-10
-12
-14
-16
-18
1.4
PBO + DMARDs
0.8
-1.16 -0.27
-0.5 -0.7
P=0.007
-5.6
-3.0 -2.8
-4.2
-7.2
-12.2
DAS28 Pt Pain
P=0.007 P=0.01
-16.2
PGA
P=0.005
P=0.001
-15.4
MDGA MDHAQ-PF TJC P=0.005
SJC
VAS
MD Global
(P=0.0502)
NS Pt PainNS
NS VAS
Patient, not physician, measures show improvement at 1 week
Yazici Y, et al. ACR 2010, Atlanta, #1808
Copyright 2010, TREG Consultants LLC
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
7
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
• 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
Copyright 2011, TREG Consultants LLC
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
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 Copyright 2011, TREG Consultants LLC
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
 with respect to F/U visits
0
1
2
DAS28 <2.6
DAS28 <2.3
SDAI
CDAI
ACR/EULAR
–0.05
mdHAQ
3
–0.1
–0.15
4
 mdHAQ according to dd
by DAS28-CRP <2.6 rem
0.2
mdHAQ
0
0
1
2
3
4
–0.2
dd
–0.4
–0.2
–0.25
0
–0.6
No. of yearly visits in remission
4
4–11
11–22
>22
No. of yearly visits in 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
Copyright 2011, TREG Consultants LLC
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
% no Δ mHAQ, 3–12 mo
69.6
73.6
69.8
72.6
Different numbers of patients achieve remission, but no difference in
predicting physical function
Uhlig T, et al. ACR 2011, Chicago, #1229
Copyright 2011, TREG Consultants LLC
www.TREGdocs.com
BRASS: Radiological progression in remission by new
ACR/EULAR criteria vs other criteria
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
MDHAQ page 1
MDHAQ page 2
RAPID3
(Routine Assessment of Patient Index Data 3)
RAPID3
(Routine Assessment of Patient Index Data 3)
– RAPID3
• 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)
DAS28 and RAPID3 RA Categories
DAS28 Categories
<2.6
2.6-3.19
3.2-5.1
>5.1
=
=
=
=
Remission
Low DAS
Moderate DAS
High DAS
RAPID3 Categories
< 3.0
3.01-6
6.01-12.0
>12.0
=
=
=
=
Near Remission
Low Severity
Moderate Severity
High Severity
RAPID3 vs DAS28 in 285 RA Patients
Spearman
correlation
rho = 0.657
24
Pincus T, et al. J Rheumatol. 2008;35:2136-2147.
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%)
Total
161 (56%)
124 (44%)
285
DAS28
25
Pincus T, et al. J Rheumatol. 2010
Time Needed to Score Various RA Measures
MD #1
120
MD #2
MD #3
MD Median
Seconds
100
80
60
40
20
0
MD #1
MD #2
MD #3
MD Median
26
28 JT
HAQ-DI
RAPID3
84
113
71
90
41.5
42.2
***
41.9
9.2
12.1
9.1
9.6
Yazici Y, et al. J Rheumatol. 2008;35:603.
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
NYU ARMD Registry
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).
RAPID3 components
ACR Core Dataset by Remission
Age (Years)
Duration (Years)
Function [0-10]
Pain [0-10]
Global [0-10]
MD Global [0-10]
Swollen [0-28]
Tender [0-28]
ESR (mm/hr)
CRP (mg/dL)
Remission Criteria
RAPID3
ACR/EULAR
52.7 (15.6)
56.1 (8.1)
4.8 (6.2)
3.9 (2.6)
0.3 (0.5)
0.5 (0.6)
0.6 (0.6)
0.6 (0.6)
0.4 (0.6)
0.3 (0.4)
1.0 (1.1)
0.6 (0.6)
0.1 (0.4)
0.2 (0.4)
0.7 (2.0)
0.2 (0.4)
17.5 (15.6)
22.0 (16.1)
2.4 (4.5)
0.3 (0.2)
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