Talk: Reduced Radiographic Progression in Patients with Early Rheumatoid Arthritis (RA) Treated with Abatacept + Methotrexate Compared to Methotrexate Alone: 24 Month Outcomes (2009 ACR/ARHP Annual Scientific Meeting)

Sunday, October 18, 2009: 5:30 PM

103 A (Pennsylvania Convention Center)

J. Bathon¹, H. Genant², S. Nayiager³, J. Wollenhaupt⁴, P. Durez⁵, J. Gómez-Reino⁶, W. Grassi⁷, B. Haraoui⁸, W. Shergy⁹, SH Park¹⁰, M. Robles¹¹, C. Peterfy¹², J.-C. Becker¹³, A. Covucci¹³, R. Helfrick¹³ and R. Westhovens¹⁴, ¹Johns Hopkins Univ Sch of Med, Baltimore, MD, ²University of California, San Francisco, CA, ³St Augustine's Hospital, Durban, South Africa, ⁴Klinikum Eilbek, Hamburg, Germany, ⁵Univ Catholique de Louvain, Brussels, Belgium, ⁶Hospital Clinico Univ De Santiago, A Coruna, Spain, ⁷Univ Politecnica delle Marche, Ancona, Italy, ⁸Institut de Rhumatolgie de Montreal, Montreal, QC, ⁹Univ of Alabama, Huntsville, AL, ¹⁰Kangnam St Mary's Hosp, Seoul, South Korea, ¹¹Centrol Medico Toluca, Mentpec, Mexico, ¹²SYNARC, Inc, San Francisco, CA, ¹³Bristol-Myers Squibb, Princeton, NJ, ¹⁴UZ Gasthuisberg, KU Leuven, Leuven, Belgium

Presentation Number: 639

Purpose Radiographic progression early in the course of RA disease may translate into long term detrimental outcomes. Here we report the 24 month radiographic outcomes in methotrexate (MTX)-naïve patients with early, erosive RA and poor prognostic factors who are treated early with abatacept (ABA) + MTX compared to MTX alone.

Method The AGREE trial was a 24-month study, with a 12-month double-blind (DB) and a 12-month open-label (OL) period, in adult MTX-naïve patients with early, erosive RA and poor prognostic factors. During the DB, patients were randomized to ABA (~10 mg/kg dose based on weight range) + MTX (dosed up to 20 mg) or placebo (PLA) + MTX. All pts received ABA + MTX during the OL. Radiographic outcomes were assessed using Genant-modified Sharp scores. Changes in erosions [ES], joint space narrowing [JSN] and total score [TS] are reported. A change in TS <= 0 defined nonprogressors.

Results Of the 459 pts completing DB and entering OL, 94.3% completed the study. Changes in radiographic outcomes from baseline to year 1 and year 1 to year 2 are presented in the table. From baseline through 24 months, patients originally randomized to the ABA + MTX arm experienced less progression of structural damage as measured by change in TS (0.84 vs 1.75) and a greater proportion of nonprogressors (56.8% vs 43.8%) compared to those originally randomized to MTX monotherapy. Moreover, among patients originally randomized to ABA + MTX arm, there was an increasing degree of inhibition of progression seen in year 2 compared to year 1 (TS = 0.18 vs 0.66, respectively, P<0.0001), with 91.1% of year 1 nonprogressors remaining nonprogressors in year 2 compared to patients initiated on MTX alone.
Radiographic Outcomes*
Mean change Genant-modified Sharp Score
ABA + MTX (N=213)
MTX Alone (DB) → ABA + MTX (OL)
(N=192)
Baseline to Yr 1
Yr 1 to Yr 2
Baseline to Yr 1
Yr 1 to Yr 2
ES
0.50
0.09
1.26
0.13
JSN
0.16
0.09
0.22
0.12
TS
0.65
0.18
1.48
0.25
* Data are reported as observed for all treated subjects in open label

Conclusion Early use of combination therapy with ABA and MTX results in greater long-term sustainable radiographic benefit in MTX-naïve early RA patients than MTX alone and supports the use of abatacept earlier in the RA disease process.

Keywords: abatacept, radiography and rheumatoid arthritis, treatment

Disclosure: J. Bathon, Biogen-Idec, Merck Serono, 2, Crescendo Biosciences, Roche, UCB, 5 ; H. Genant, Synarc, Inc., 1, Bristol-Myers Squibb, Roche, Genentech, Pfizer, Amgen, Merck, Servier, Biogen-Idec, Lilly, 2, Bristol-Myers Squibb, Roche, Merck, Lilly, Genentech, Amgen, Servier, Synarc, 5 ; S. Nayiager, None; J. Wollenhaupt, Bristol-Myers Squibb, 5 ; P. Durez, UCL, 3, Bristol-Myers Squibb, Roche, Centocor, Abbott, Wyeth, 5, UEMS, Royal Belgian Society of Rheumatology, 6, Bristol-Myers Squibb, 8 ; J. Gómez-Reino, Wyeth, Schering-Plough, Bristol-Myers Squibb, Roche, 6, Abbott, Wyeth, Roche, Bristol-Myers Squibb, Schering-Plough, 9 ; W. Grassi, Abbott Immunology, Wyeth, 2, Bristtol-Myers Squibb, Abbott Immunology, Schering-Plough, 5, Bristol-Myers Squibb, Abbott Immunology, General Electric, Esaote, Schering-Plough, Roche, Wyeth, 9 ; B. Haraoui, Abbott, Amgen, Bristol-Myers Squibb, Roche, Shering-Plough, UCB, Wyeth, 2, Abbott, Amgen, Bristol-Myers Squibb, Roche, Shering-Plough, UCB, Wyeth, 5, Abbott, Amgen, Bristol-Myers Squibb, Roche, Shering-Plough, UCB, Wyeth, 8 ; W. Shergy, Amgen, Wyeth, Abbott, Bristol-Myers Squibb, Centocor, Genentech, Biogen-Idec, 9 ; S. Park, None; M. Robles, None; C. Peterfy, Synarc, Inc., 1, Synarc, Inc., 3 ; J. -. C. Becker, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3, Bristol-Myers Squibb ; A. Covucci, Bristol-Myers Squibb, 3 ; R. Helfrick, Bristol-Myers Squibb, 3 ; R. Westhovens, Bristol-Myers Squibb, 8, Bristol-Myers Squibb, Schering-Plough, Centocor, Roche, 5, UCB , 2 .

639 - Reduced Radiographic Progression in Patients with Early Rheumatoid Arthritis (RA) Treated with Abatacept + Methotrexate Compared to Methotrexate Alone: 24 Month Outcomes