Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Clinical remission is associated with better long-term outcomes1,2 and should be the goal of therapy in RA. In the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial, greater percentages of patients (pts) achieved DAS28 (CRP) <2.6 following 12 mths of treatment with SC abatacept + MTX and 6 mths after withdrawal of all RA therapy, compared with MTX alone. At most time points, abatacept monotherapy was more effective than MTX alone.1 Here, we report clinical efficacy and remission rates from AVERT, using stringent criteria at Mth 12 and after treatment withdrawal (Mth 18).
Methods: AVERT enrolled pts who were MTX-naïve, anti-cyclic citrullinated peptide 2 seropositive (CCP2+), aged ≥18 yrs, with active synovitis ≥2 joints for ≥8 wks, DAS28 (CRP) ≥3.2, and disease onset of ≤2 yrs. Pts were randomized to 12 mths of weekly SC abatacept (125 mg) + MTX, SC abatacept (125 mg) or MTX. All RA treatment was withdrawn after 12 mths (abatacept immediately, MTX and steroids over 1 mth) in pts with DAS28 (CRP) <3.2. Percentages (%) of pts achieving DAS28 (CRP) <2.6 or <2.4, Major Clinical Response (MCR: ACR70 response for ≥6 consecutive mths), or remission (CDAI ≤2.8, SDAI ≤3.3, Boolean criteria) at Mth 12, and the % who maintained these reduced disease activity states at Mth 18 were analyzed.
Results: 351 pts with early RA were enrolled (n=119, abatacept + MTX; n=116, abatacept monotherapy; n=116, MTX alone). Mean characteristics at baseline were: disease duration 0.6 yrs, DAS28 (CRP) 5.4, HAQ-DI 1.4, 95.2% RF+ and anti-CCP2+). At Mth 12, higher % of pts in the abatacept + MTX group achieved DAS28 (CRP) <2.6 (primary analysis) as well as the more stringent clinical endpoint DAS28 (CRP) <2.4 or remission (CDAI, SDAI, Boolean), compared with MTX alone (Table). Rates of low disease activity and remission with abatacept monotherapy were intermediate between abatacept + MTX and MTX alone (Table). Higher % (95% CI) of abatacept-treated pts achieved MCR at Mth 12, compared with MTX alone (abatacept + MTX and abatacept monotherapy vs MTX alone: 31.9% [23.6, 40.3] and 17.2% [10.4, 24.1] vs 8.6% [3.5, 13.7]). Following treatment withdrawal, a small but higher % of abatacept-treated pts (with MTX or monotherapy) sustained low disease activity or remission than in the MTX group (Table).
|
Criteria |
Reduced disease activity |
Sustained levels of |
||||
|
|
Abatacept (n=119) |
Abatacept monotherapy (n=116) |
MTX
(n=116) |
Abatacept (n=84) |
Abatacept monotherapy (n=66) |
MTX
(n=73) |
|
Primary analysis |
||||||
|
DAS28 (CRP) <2.6* |
60.9% |
42.5% |
45.2% |
14.8% (8.3, 21.3) |
12.4% (6.3, 18.5) |
7.8% (2.9, 12.7) |
|
Abatacept plus MTX vs MTX alone: Abatacept monotherapy vs MTX alone: OR (95% CI): 0.9 (0.6, 1.6) |
Abatacept plus MTX vs MTX alone: Abatacept monotherapy vs MTX alone: OR (95% CI): 2.0 (0.8, 5.1) |
|||||
|
Stringent clinical endpoint |
||||||
|
DAS28 (CRP) <2.4*† |
53.0% |
38.1% |
36.5% |
13.0% |
9.7% |
3.5% |
|
Abatacept plus MTX vs MTX alone: Abatacept monotherapy vs MTX alone: OR (95% CI): 1.1 (0.7, 1.9) |
Abatacept plus MTX vs MTX alone: Abatacept monotherapy vs MTX alone: OR (95% CI): 5.1 (1.4, 18.2) |
|||||
|
Stringent remission criteria |
||||||
|
CDAI ≤2.8 |
42.0%‡ (33.2, 50.9) |
31.0% |
27.6% |
9.2% |
9.5% |
5.2% |
|
SDAI ≤3.3 |
42.0%‡ |
29.3% |
25.0% |
9.2% |
7.8% |
6.0% |
|
Boolean |
37.0%‡ |
26.7% |
22.4% |
6.7% |
6.0% |
1.7% |
|
OR, odds ratio Percentages calculated using all randomized patients (N=351), unless otherwise stated. Data given as % (95% CIs). *Percentages from adjusted logistic regression analysis. †Percentages calculated using 115 (abatacept plus MTX) or 116 (abatacept monotherapy and MTX-alone treatment arms) patients. ‡p<0.05 for treatment difference vs MTX (95% CI for the estimate of treatment difference did not cross 0) |
||||||
Conclusion: In early RA, abatacept + MTX for 12 mths resulted in higher rates of low disease activity and remission according to stringent criteria, than MTX alone. Few pts who achieved these stringent clinical measures at 12 mths could maintain them 6 mths after all RA treatment had been withdrawn. These findings indicate that treatment with abatacept + MTX early in the course of RA can achieve high remission rates at 12 mths, which may be sustained on withdrawal of all RA therapy in a small but higher proportion of pts than using MTX alone.
References:
1. Westhovens R, et al. Ann Rheum Dis 2009;68:1870–7.
2. Emery P, et al. Ann Rheum Dis 2010;69:510–6.
Disclosure:
G. Burmester,
AbbVie, Pfizer, Roche, UCB,
2,
AbbVie, BMS, MSD, Medimmune, Novartis, Pfizer, Roche, Sandoz, UCB,
5,
AbbVie, BMS, MSD, Pfizer, Roche, Sandoz, UCB,
8;
D. E. Furst,
AbbVie, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB,
2,
AbbVie, Actelion, Amgen, BMS, Cytori, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB,
5,
AbbVie, Actelion, UCB ,
8;
B. G. Combe,
Pfizer, Roche-Chugai,
2,
BMS, Merck, Pfizer, Roche-Chugai, UCB,
8;
T. W. J. Huizinga,
Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Inc, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, UCB, Inc., Eli Lilly,
5,
Meteor Board,
6,
EU & Dutch Arthritis Foundation,
2,
Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough,
8,
Abbott Laboratories, Roche,
9;
V. P. Bykerk,
Amgen, Pfizer, BMS, Janssen, UCB, Roche/Genentech,
2;
D. Wong,
Bristol-Myers Squibb,
1,
Bristol-Myers Squibb,
3;
C. S. Karyekar,
Bristol-Myers Squibb,
3;
P. Emery,
AbbVie, BMS, Merck, Pfizer, Roche, Takeda,
5,
AbbVie, BMS, Merck, Pfizer, Roche,
2.
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