Yusuf Yazıcı, MD NYU Hospital for Joint Diseases, New York
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Remission In Rheumatoid Arthritis (RA):How Will The New Criteria Change Our
Approach To RA Treatment?
Yusuf Yazıcı, MDNYU Hospital for Joint Diseases, New York
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Disclosures
• Abbott• BMS• Celgene• Centocor• Genentech• Janssen• Merck• Pfizer• Roche• Takeda• UCB
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Background
• Early, aggressive treatment• Measurement tools• Treat to target• Routine monitoring
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Why Do We Need to Measure?% 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
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
DAS28 score, mean 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
• 102 patients with RA on conventional treatment, judged by their rheumatologist to be in remission
Brown AK et al. Arthritis Rheum. 2008;58:2958-2967.
Association between baseline findings and radiographic progression over 12 months
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ACR Core Data Set
1. Swollen joint count2. Tender joint count3. Physician Global Assessment
4. ESR or CRP
5. Physical Function (HAQ, MHAQ, MDHAQ)6. Pain7. Patient Global Assessment
8. Radiographs
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Clinical Measurement Tools
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.
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ACR20 DAS28 SDAI CDAI GAS ERAM RADAI RADARA RAPID3
Outcome Measures in RA
Patient function
Patient pain
Patient global
MD global
# Tender joints
# Swollen joints
ESR or CRP
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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
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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.
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Patient-Reported Outcomes:Placebo Response at 6 Months
Strand V et al. Rheumatol. 2004;43:640-647.
21.4 20.3
11.7 11.6
-20.4
-9.3
-2.8
-21.5
-2.4
-25
-20
-15
-10
-5
0
5
10
15
20
25
TJCSJC Phys Global
Pain (VAS)
Pt Global
HAQ (mean) ESR CRP
HAQ DI
Physician-derived Patient-derived Laboratory
% C
han
ge
fro
m B
asel
ine
Imp
rove
me
nt
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Copyright 2010, TREG Consultants LLC
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
Yazici Y, et al. ACR 2010, Atlanta, #1808
Patient, not physician, measures show improvement at 1 week
Pt Pain VASMD Global VAS
P=0.007
P=0.001
P=0.005
-1.16
-12.2
-16.2
-0.27
1.4 0.8
-18-16-14-12-10
-8-6-4-202
Me
an
ch
an
ge
fro
m B
L
DAS28 Pt Pain PGA-15.4
-0.5
-4.2-3.0
-5.6
-0.7
-7.2
-2.8
MDGA MDHAQ-PF SJCTJC
TCZ 8 mg/kg + DMARDs PBO + DMARDs
P=0.007 P=0.01 P=0.005 (P=0.0502) NS NS NS
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Copyright 2011, 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
1. Kuriya B, et al. EULAR 2011, London, #SAT0405; 2. Bernard M, et al. Ibid, #OP0027
All remission is not the same1,2
• 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)
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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
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Copyright 2011, TREG Consultants LLC
HAQ improvement and time in remission in RA patients using various criteria
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
• BRASS Registry: pts with >2 y F/U; more time in remission better HAQ
0
md
HA
Q
–0.1
–0.05
–0.25
–0.15
–0.2
1 2 3 40
No. of yearly visits in remission
DAS28 <2.6DAS28 <2.3SDAICDAIACR/EULAR
with respect to F/U visits
No. of yearly visits in remission
0
0.2
–0.2
–0.6
–0.4
1 2 3 40
44–1111–22>22
md
HA
Q
mdHAQ according to dd by DAS28-CRP <2.6 rem
dd
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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)
Uhlig T, et al. ACR 2011, Chicago, #1229
Different numbers of patients achieve remission, but no difference in predicting physical function
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
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BRASS: Radiological progression in remission by new ACR/EULAR criteria vs other criteria
www.TREGdocs.com
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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
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MDHAQ page 1
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MDHAQ page 2
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RAPID3 (Routine Assessment of Patient Index Data 3)
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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)
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DAS28 and RAPID3 RA Categories
DAS28 Categories
<2.6 = Remission2.6-3.19 = Low DAS3.2-5.1 = Moderate DAS>5.1 = High DAS
RAPID3 Categories
< 3.0 = Near Remission3.01-6 = Low Severity6.01-12.0 = Moderate Severity>12.0 = High Severity
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RAPID3 vs DAS28 in 285 RA Patients
Spearmancorrelation
rho = 0.657
Pincus T, et al. J Rheumatol. 2008;35:2136-2147.
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RAPID3 & DAS28 Categories are Correlated Significantly in 285 Patients at 3 Sites
DAS28
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
Pincus T, et al. J Rheumatol. 2010
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Time Needed to Score Various RA Measures
0
20
40
60
80
100
120S
eco
nd
sMD #1 MD #2 MD #3 MD Median
MD #1 84 41.5 9.2
MD #2 113 42.2 12.1
MD #3 71 *** 9.1
MD Median 90 41.9 9.6
28 JT HAQ-DI RAPID3
Yazici Y, et al. J Rheumatol. 2008;35:603.
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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
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NYU ARMD Registry
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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).
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RAPID3 components
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ACR Core Dataset by RemissionRemission Criteria
RAPID3 ACR/EULARAge (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) 0.6 (0.6)Global [0-10] 0.4 (0.6) 0.3 (0.4)MD Global [0-10] 1.0 (1.1) 0.6 (0.6)Swollen [0-28] 0.1 (0.4) 0.2 (0.4)Tender [0-28] 0.7 (2.0) 0.2 (0.4)ESR (mm/hr) 17.5 (15.6) 22.0 (16.1)CRP (mg/dL) 2.4 (4.5) 0.3 (0.2)
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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