1238 - Clinical Response At Months 1–6 Can Predict Likelihood of Achieving Remission in Abatacept Plus Methotrexate-Treated Patients with Early Rheumatoid Arthritis

Monday, November 7, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Yusuf Yazici, NYU Hospital for Joint Diseases, New York, NY, Jurgen Wollenhaupt, Schoen-Klinik Hamburg-Eilbek, Hamburg, Germany, Patrick Durez, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium, Juan J. Gomez-Reino, Hospital Clinico Universitario, Santiago de Compostela, Spain, Walter Grassi, Università Politecnica delle Marche, Ancona, Italy, Manuela Le Bars, Bristol-Myers Squibb, Rueil-Malmaison, France, Corine Gaillez, Bristol-Myers Squibb, Rueil Malmaison, France, Coralie Poncet, Docs International, Issy les Moulineaux, France, Ayanbola Elegbe, Bristol-Myers Squibb, Princeton, NJ and Rene Westhovens, UZ Gasthuisburg, Leuven, Belgium
Presentation Number: 1238

Background/Purpose: ACR/EULAR treat-to-target recommendations define remission as the goal for patients (pts) with early rheumatoid arthritis (RA), with appropriate therapeutic adaptation every 3–6 mths dependent on response1. In the AGREE study, a large proportion of methotrexate (MTX)-naïve pts with early RA achieved DAS28 remission over 1 yr; 41 (95% CI: 35–47) vs 23% (18–29) for pts treated with abatacept (ABA) + MTX vs MTX alone (p<0.001)2. Applying a threshold of a change from baseline (BL) in DAS28 of >0.6 (DAS28 response) or ≥1.2 (clinically meaningful DAS28 response) during the first few mths of therapy may help identify pts more likely to reach Low Disease Activity State (LDAS) or remission at a later time-point. We present post-hoc analyses examining if a DAS28 response or a clinically meaningful DAS28 response at Mths 1–6 can predict likelihood of achieving remission or LDAS at Yr 1, in pts treated with ABA + MTX.

Method: 

In the 1-yr double-blind (DB) period of AGREE, MTX-naïve pts with early (≤2 yrs) RA, poor prognostic factors and high disease activity, as evidenced by tender (≥12) and swollen (≥10) joint counts, were randomized 1:1 to ABA + MTX or placebo + MTX (MTX alone)2. All pts completing the DB period entered the open-label (OL) period to receive ABA + MTX. Remission was defined as DAS28-CRP <2.6 and LDAS as ≤3.2. Likelihood of achieving remission at Yr 1 was evaluated for pts with a DAS28 response (change from BL >0.6) or a clinically meaningful DAS28 response (change from BL ≥1.2) at Mths 1–6. Data are as observed for pts treated with ≥1 dose of ABA in the OL period.    

Result: Analyses included 459 pts; 232 treated with ABA + MTX and 227 with MTX alone. BL characteristics were similar between groups1; mean (SD) DAS28-CRP was 6.3 (1.0) in each group. Over 90% of ABA + MTX-treated pts experienced a DAS28 response (change from BL >0.6) from Mths 2 through 6, compared with ~73–88% of MTX-alone treated pts (Table). For pts with DAS28 response at Mths 2 through 6, approximately 50% of ABA + MTX-treated pts achieved remission at Yr 1, vs ~30% of MTX-alone treated pts (Table); for these pts, >60% of the ABA + MTX group vs 44–48% of the MTX alone group achieved LDAS at Yr 1 (data not shown). Through Mths 2 to 6, 76–88% of ABA + MTX-treated pts achieved a clinically meaningful DAS28 response (change from BL ≥1.2) vs 50–76% of MTX alone-treated pts (Table). Among these pts, ~50% of the ABA + MTX-treated group achieved remission at Yr 1 vs ~30% of MTX-alone treated group (Table); ~70% and 50–54% from each group, respectively, achieved LDAS (data not shown).

 

 

Month 1

Month 2

Month 3

Month 4

Month 5

Month 6

DAS28 response (change from baseline >0.6), % (n/N)

ABA + MTX

77.2 (173/224)

90.8 (208/229)

92.1 (211/229)

93.9 (215/229)

95.2 (216/227)

95.1 (213/224)

MTX alone

53.4 (119/223)

72.6 (162/223)

76.6 (170/222)

86.7 (195/225)

88.1 (192/218)

87.6 (191/218)

DAS28 remission at Year 1, % (n/N), according to achievement of DAS28 response each month

ABA + MTX

49.1 (85/173)

48.1 (100/208)

47.9 (101/211)

47.4 (102/215)

46.8 (101/216)

47.9 (102/213)

MTX alone

32.8 (39/119)

30.2 (49/162)

27.6 (47/170)

27.7. (54/195)

29.2 (56/192)

29.8 (57/191)

Clinically meaningful DAS28 response (change from baseline ≥1.2), % (n/N)

ABA + MTX

54.0 (121/224)

75.5 (173/229)

79.0 (181/229)

84.7 (194/229)

85.9 (195/227)

88.8 (199/224)

MTX alone

31.4 (70/223)

49.8 (111/223)

58.6 (130/222)

68.9 (155/225)

74.8 (163/218)

76.1 (166/218)

DAS28 remission at Year 1, % (n/N), according to achievement of clinically meaningful DAS28 response each month

ABA + MTX

54.5 (66/121)

53.2 (92/173)

52.5 (95/181)

52.6 (102/194)

51.3 (100/195)

50.8 (101/199)

MTX alone

38.6 (27/70)

34.2 (38/111)

33.1 (43/130)

31.6 (49/155)

31.3 (51/163)

31.9 (53/166)

DAS28=Disease Activity Score 28; ABA=abatacept; MTX=methotrexate;

Conclusion: 

ABA + MTX-treated pts who achieve a DAS28 response (change from BL >0.6), or a clinically meaningful DAS28 response (change from BL ≥1.2), during the first 6 mths of therapy have a higher likelihood (~50%) of achieving remission at Yr 1 vs  MTX-alone treated pts (~30%). These data support the concept of treating-to-target1 with ABA + MTX in pts with early RA.

1Smolen J, et al. ARD 2010;69:631–7

1Westhovens R, et al. ARD 2009;68:1870–7


Keywords: abatacept and clinical trials

Disclosure: Y. Yazici, Centocor, Inc, Bristol-Myers Squibb, 2, Bristol-Myers Squibb, Celgene, Genentech, UCB, Roche, Pfizer, 5, Bristol-Myers Squibb, Genentech, 8 ; J. Wollenhaupt, Bristol-Myers Squibb, Chugai, Roche, 5, Chugai, Roche, 8, Bristol-Myers Squibb, 9 ; P. Durez, Bristol-Myers Squibb, 8 ; J. J. Gomez-Reino, Hoffmann-La Roche, Inc., Roche, Schering-Plough, UCB, Inc, 5, Roche, Schering-Plough, Wyeth Pharmaceuticals, 2, Bristol-Myers Squibb, Roche, Schering-Plough, UCB, Inc, 8 ; W. Grassi, Abbott, Brystol Myers Squibb, Esaote, General Electric, Menarini, Merck Sharp & Dohme, Pfizer, Roche, Schering-Plough, UCB, 5, Abbott, Brystol Myers Squibb, Esaote, General Electric, Menarini, Merck Sharp & Dohme, Pfizer, Roche, Schering-Plough, UCB, 2 ; M. Le Bars, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3 ; C. Gaillez, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3 ; C. Poncet, None; A. Elegbe, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3 ; R. Westhovens, Bristol-Myers Squibb, Centocor, Inc., Roche, Schering-Plough, 5, Roche, UCB, Inc., 2, Bristol-Myers Squibb, 8 .