1224 - Remission According to Different Composite Disease Activity Indices in Biologic-na´ve Patients with Rheumatoid Arthritis Treated with Abatacept or Infliximab Plus Methotrexate

Monday, November 7, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Josef S. Smolen1, Maxime Dougados2, Corine Gaillez3, Coralie Poncet4, Manuela Le Bars3, Monica Mody5 and Michael H. Schiff6, 1Medical University of Vienna and Hietzing Hospital, Vienna, Austria, 2H˘pital Cochin, Paris, France, 3Bristol-Myers Squibb, Rueil Malmaison, France, 4Docs International, SÚvres, France, 5Bristol-Myers Squibb, Princeton, NJ, 6University of Colorado, Denver, CO
Presentation Number: 1224

Background/Purpose: Levels of acute phase reactants correlate with clinical disease activity in rheumatoid arthritis (RA)1, and are weighted differently – or not included – in the calculation of disease activity indices such as SDAI, CDAI and DAS28. Biologics with different mechanisms of action (TNF blockers, anti-IL6 agent, T-cell costimulation modulator) may impact both acute phase reactants and disease activity measures differently2. We evaluated remission using the new definition of remission according to ACR/EULAR3 versus DAS28-defined remission in RA patients (pts) treated with abatacept, infliximab or placebo plus MTX in the ATTEST trial, and investigated the contributions of the different core components.

Method: In ATTEST, biologic-naïve pts with RA and an inadequate response to MTX were randomized to abatacept (~10 mg/kg every 4 wks), infliximab (3 mg/kg every 8 wks), or placebo (every 4 wks), plus MTX4. Remission according to DAS28 (CRP), SDAI and CDAI at Month 6 were evaluated for abatacept- infliximab- and placebo-treated pts, with missing data imputed by LOCF; SDAI and CDAI were evaluated post-hoc. Cut-offs for remission were <2.6 for DAS28; ≤3.3 for SDAI; and ≤2.8 for CDAI. Mean scores (with SD) from baseline at Month 6 in individual disease activity measures were assessed for pts in remission at Month 6.

Result: Baseline demographics and clinical characteristics were comparable between groups4. Mean (SD) DAS28, SDAI and CDAI scores, respectively, were 6.4 (0.9), 48.8 (13.2) and 45.7 (12.2) for abatacept, 6.4 (0.9), 48.4 (13.1) and 45.1 (12.3) for infliximab, and 6.3 (0.8), 48.3 (12.0) and 45.6 (11.2) for placebo. At Month 6, similar treatment effects for remission were observed for abatacept and infliximab, independent of indices used (Table). Among abatacept-treated pts in DAS28 remission, 46.7 and 56.7% also achieved SDAI and CDAI remission, respectively, compared with 43.6 and 43.6% of infliximab-treated pts. In patients reaching remission at Month 6, mean scores for core components, including ESR and CRP, were generally similar between the two active treatment arms (Table), although numerically lower SJC were seen with abatacept versus infliximab for patients in DAS28 remission.

 

 

Abatacept, n=156

Infliximab, n=165

Placebo, n=110

 

DAS28

SDAI

CDAI

DAS28

SDAI

CDAI

DAS28

SDAI

CDAI

Remission at
Month 6, n (%)

95% CI

30

(19.2)

13.0–25.4 

14

(9.0)

4.5–13.5 

18

(11.5)

6.5–16.6

39

(23.8)

17.3–30.3

17

(10.4)

5.7–15.0

20

(12.2)

7.2–17.2

6

(5.5)

1.2–9.7

4

(3.6)

1.0–9.0

5

(4.5)

0.7–8.4

Mean (SD) scores at Month 6 for patients in remission

SJC

0.3

(0.6)

0.2

(0.6)

0.2

(0.6)

1.0

(1.4)

0.2

(0.6)

0.2

(0.4)

1.7

(2.3)

0.3

(0.5)

0.2

(0.5)

TJC

0.2

(0.4)

0.1

(0.4)

0.2

(0.4)

0.3

(0.7)

0.1

(0.2)

0.2

(0.4)

0.0

(0.0)

0.3

(0.5)

0.4

(0.6)

PGA

12.4

(12.5)

5.0

(5.8)

6.4

(7.2)

13.6

(12.3)

6.5

(4.7)

7.3

(6.2)

9.2

(5.5)

7.0

(7.4)

6.6

(6.4)

EGA

8.3

(8.0)

3.2

(2.7)

3.5

(3.0)

8.7

(9.9)

3.8

(2.4)

3.4

(2.1)

10.7

(8.2)

5.0

(6.7)

4.8

(5.8)

ESR

21.2

(9.9)

17.9

(10.4)

19.6

(11.2)

26.6

(19.7)

27.5

(24.0)

30.8

(22.2)

33.3

(30.4)

41.0

(36.1)

51.2

(38.7)

CRP

7.9

(6.6)

6.8

(7.7)

14.4

(26.8)

5.3

(4.6)

4.9

(3.4)

9.2

(12.0)

9.2

(3.9)

9.8

(1.5)

12.3

(5.8)

CI=confidence intervals; SD=standard deviation; DAS28=Disease Activity Score 28; SDAI=simplified disease activity index; CDAI=clinical disease activity index; SJC=swollen joint count; TJC=tender joint count; PGA=patient global assessment; EGA=evaluator global assessment; ESR=erythrocyte sedimentation rate; CRP=C-reactive protein

Conclusion: Remission rates at Month 6 were similar for abatacept and infliximab, irrespective of the type of composite measure used. This remained true when more stringent remission criteria, such as SDAI, were applied. Furthermore, mean TJC and SJC for abatacept-treated patients in DAS28 remission were similar to patients in SDAI and CDAI remission, suggesting that these patients are not experiencing residual disease activity as has been seen for patients in DAS28 remission treated with other biologics2.

1Mallya RK, et al. J Rheumatol 1982;9:224–8

2Smolen JS, Aletaha D. Arthritis Rheum 2011;63:43–52

3Felson DT, et al. Ann Rheum Dis 2011;70:404–413

4Schiff M, et al. Ann Rheum Dis 2008;67;1096–103


Keywords: abatacept, clinical trials, infliximab, remission and rheumatoid arthritis (RA)

Disclosure: J. S. Smolen, Bristol-Myers Squibb, 2, Bristol-Myers Squibb, 5 ; M. Dougados, Bristol-Myers Squibb, 5, Bristol-Myers Squibb, 2, Bristol-Myers Squibb, 8 ; C. Gaillez, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3 ; C. Poncet, None; M. Le Bars, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3 ; M. Mody, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3 ; M. H. Schiff, Bristol-Myers Squibb, 5 .