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

Disclosures

• Abbott• BMS• Celgene• Centocor• Genentech• Janssen• Merck• Pfizer• Roche• Takeda• UCB

Background

• Early, aggressive treatment• Measurement tools• Treat to target• Routine monitoring

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

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

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

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

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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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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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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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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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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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

BRASS: Radiological progression in remission by new ACR/EULAR criteria vs other criteria

www.TREGdocs.com

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 = 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

26

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.

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 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)

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