ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1521

Sustained Improvements in Magnetic Resonance Imaging Outcomes with Abatacept Following the Withdrawal of All Treatment in Patients with Early Rheumatoid Arthritis

C Peterfy1, Gerd Burmester2, Vivian P. Bykerk3, B G Combe4, J C DiCarlo1, Daniel E. Furst5, T W J Huizinga6, C S Karyekar7, D Wong7, Philip G. Conaghan8 and P Emery9, 1Spire Sciences, Inc., Boca Raton, FL, 2Charité – University Medicine Berlin, Berlin, Germany, 3Hospital for Special Surgery, Weill Cornell Medical College, New York, NY, 4Hôpital Lapeyronie, Montpellier, France, 5University of California at Los Angeles, Los Angeles, CA, 6Leiden University Medical Center, Leiden, Netherlands, 7Bristol-Myers Squibb, Princeton, NJ, 8NIHR-Leeds Musculoskeletal Biomedical Research Unit and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, 9University of Leeds, Leeds, United Kingdom

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Novel therapies, Biosimilars, Strategies and Mechanisms in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Biologic treatment can lead to improved clinical outcomes in early RA. In the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) study, abatacept (ABA) + MTX achieved significantly higher rates of DAS-defined remission (DAS28 [CRP] <2.6) vs MTX alone at 12 mths of treatment; a small but significantly higher number of patients (pts) on ABA + MTX vs MTX alone sustained remission following the rapid withdrawal of all RA drugs.1 To assess the progression of structural joint damage in pts with early RA in AVERT, MRI changes were evaluated after 12 mths on treatment and following the withdrawal of all RA medication in pts in DAS-defined remission or LDA. Methods: Pts with DAS28 (CRP) ≥3.2, onset of symptoms ≤2 yrs, active synovitis in ≥2 joints, who were MTX-naïve and anti-cyclic citrullinated peptide (CCP2) positive were randomized to SC ABA 125 mg/wk + MTX, SC ABA 125 mg/wk monotherapy or MTX alone for 12 mths. All RA treatment was removed after 12 mths (ABA immediately and MTX and steroids tapered over 1 mth) in pts with DAS28 (CRP) <3.2. Gadolinium-enhanced MRI of the clinically worse hand/wrist was performed at baseline and at Mths 6, 12, 18 and 24. Adjusted mean changes from baseline in synovitis, osteitis and erosion were calculated at Mths 12 and 18 for pts with MRI assessments. In a post hoc analysis, adjusted mean changes from baseline in synovitis, osteitis and erosion MRI scores were compared in pts who had DAS28 (CRP) <2.6 at both Mths 12 and 18 (after withdrawal). Results: Pts in the intent-to-treat population had early RA (mean symptom duration 0.56 yrs) with highly inflammatory disease (mean TJC 23.3, SJC 16.5, CRP 17.5 mg/dL), severe disease activity (mean DAS28 [CRP] 5.44 and HAQ-DI 1.42), poor prognostic factors (95.2% RF and anti-CCP2 double positive) and 31.9% were on steroids at baseline (mean dose 7.0 mg/day). Improvements in synovitis and osteitis were greater, and the progression of erosion was less, in the ABA + MTX arm vs MTX, both on treatment (Mth 12) and following all treatment withdrawal (Mth 18); benefits of ABA monotherapy on synovitis at Mths 12 and 18 and osteitis at Mth 12 were intermediate to those of ABA + MTX and MTX alone (Table 1). In pts with DAS28 (CRP) <2.6 at both Mths 12 and 18, MRI benefits were maintained from Mth 12 to Mth 18 (Table 2).                            

Table 1. Adjusted mean change from baseline in MRI scores (intent-to-treat population)
Adjusted mean change from baseline (95% CI) ABA + MTX (n=119) ABA monotherapy (n=116) MTX (n=116)
Synovitis Mth 12 -2.35 (-2.89, -1.81)* n=91 -1.36 (-1.91, -0.80) n=81 -0.68 (-1.24, -0.13) n=84
Mth 18 -1.34 (-2.18, -0.50) n=38 -1.19 (-2.01, -0.31) n=35 -0.49 (-1.45, 0.46) n=29
Osteitis Mth 12 -2.58 (-3.47, -1.69)* n=91 -1.37 (-2.27, -0.46) n=81 -0.68 (-1.59, 0.24) n=84
Mth 18 -2.03 (-3.72, -0.34) n=38 0.45 (-1.31, 2.20) n=35 0.34 (-1.55, 2.24) n=29
Erosion Mth 12 0.19 (-0.46, 0.84)* n=91 1.42 (0.76, 2.07) n=81 1.53 (0.86, 2.19) n=84
Mth 18 0.13 (-0.74, 1.01)* n=38 1.85 (0.96, 2.74) n=35 2.00 (1.07, 2.93) n=29
*p<0.05 for treatment difference vs MTX (95% CI for the estimate of treatment difference did not cross 0)
 

 

Table 2. Adjusted mean change from baseline in MRI scores; post hoc analysis in pts with DAS28 (CRP) <2.6 at both Mths 12 and 18
Adjusted mean change from baseline (95% CI) ABA + MTX (n=18) ABA monotherapy (n=14) MTX (n=9)
Synovitis Mth 12 -1.95 (-2.82, -1.08) n=18 -2.43 (-3.38, -1.48) n=12 -1.25 (-2.62, 0.13) n=6
Mth 18 -2.14 (-3.14, -1.15) n=16 -2.45 (-3.49, -1.41) n=13 -1.47 (-2.85, -0.10) n=8
Osteitis Mth 12 -2.39 (-3.15, -1.63) n=18 -2.06 (-2.86, -1.26) n=12 -1.28 (-2.39, -0.16) n=6
Mth 18 -2.37 (-3.10, -1.63) n=16 -2.23 (-2.98, -1.49) n=13 -1.46 (-2.48, -0.43) n=8
Erosion Mth 12 0.18 (-0.79, 1.15) n=18 0.42 (-0.57, 1.42) n=12 1.21 (-0.16, 2.58) n=6
Mth 18 0.09 (-0.93, 1.12) n=16 0.36 (-0.70, 1.41) n=13 1.25 (-0.18, 2.68) n=8
There were no significant treatment differences vs MTX

Conclusion: Abatacept reduced MRI-detected joint inflammation and joint damage in pts with early RA; these benefits may be maintained for at least 6 mths after treatment withdrawal in pts who are in remission or low disease activity, suggesting an alteration in the autoimmune process.

  1. Emery P, et al. Ann Rheum Dis 2014;73(Suppl 2):69.  

Disclosure:

C. Peterfy,

Spire Sciences, Inc.,

1,

AbbVie, Inc., Amgen Inc., Articulinx, AstraZeneca, Bristol-Myers Squibb, Five Prime Therapeutics, Genentech, Hoffmann-La Roche, Inc., Lilly USA, LLC., Medimmune, Merck Pharmaceuticals, Moximed, Novartis Pharmaceuticals Corporation, Novo Nordisk, Plexxikon,

5,

Amgen,

8;

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;

V. P. Bykerk,

Amgen, Pfizer, BMS, Janssen, UCB, Roche/Genentech,

2;

B. G. Combe,

Pfizer, Roche-Chugai,

2,

BMS, Merck, Pfizer, Roche-Chugai, UCB,

8;

J. C. DiCarlo,

Spire Sciences, Inc.,

3;

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;

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;

C. S. Karyekar,

Bristol-Myers Squibb,

3;

D. Wong,

Bristol-Myers Squibb,

1,

Bristol-Myers Squibb,

3;

P. G. Conaghan,

Centocor Research and Development, Inc., Pfizer Inc,

2,

AbbVie, AstraZeneca, Bioiberica, BMS, Centocor, Inc., Janssen Merck Pharmaceuticals, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, UCB,

8;

P. Emery,

AbbVie, BMS, Merck, Pfizer, Roche, Takeda,

5,

AbbVie, BMS, Merck, Pfizer, Roche,

2.

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