ABATACEPT SUSTAINS INHIBITION OF RADIOGRAPHIC PROGRESSION OVER 2 YEARS IN RHEUMATOID ARTHRITIS (RA) PATIENTS WITH AN INADEQUATE RESPONSE TO METHOTREXATE (MTX): RESULTS FROM THE LONG-TERM EXTENSION (LTE) OF THE AIM TRIAL

Background: Abatacept (Aba) has demonstrated significant reduction in radiographic progression in RA patients with an inadequate response to MTX during the double-blind (DB) phase of the AIM (Aba in Inadequate responders to MTX) trial.Objectives: The effect of Aba on structural damage progression over 2 yrs was assessed during the 1-yr, DB phase and the open-label LTE phase of the Phase III AIM trial.Methods: Patients received a fixed dose of Aba (∼10 mg/kg by body weight) or placebo (Pbo) on Days 1, 15 and 29, and every 4 weeks thereafter, plus MTX for 1 yr. Patients completing the DB phase were eligible to enter the LTE (all patients were treated with a fixed dose of Aba ∼10 mg/kg every 4 weeks). Radiographs of hands and feet were performed at randomization and at 1 and 2 yrs or early termination. Paired radiographs were independently scored for erosion score (ES), joint-space narrowing (JSN) score, and total score (TS) using the Genant-modified Sharp score.Results: 433 vs 219 patients were randomized and treated with Aba vs Pbo; 385 (88.9%) vs 162 (74.0%) completed the DB phase. 539 patients were treated with Aba in the LTE. In patients treated with Aba for 2 yrs, minimal radiographic progression was observed during Yr 2 of treatment (mean change from baseline [BL] at Yr 1 vs Yr 2; Table 1). Using a linear mixed model analysis to compare the slope of radiographic progression over the 2-yr period, 2 yrs of Aba was found to be significantly better than 1 yr of Pbo followed by 1 yr of Aba (ES p<0.001; JSN p<0.05; TS p<0.01). Radiographic progression in the Aba group slowed during Yr 2 vs Yr 1 (slope from Yr 1 to Yr 2: ES: 0.6 vs 0.3; JSN: 0.4 vs 0.4; TS: 1.0 vs 0.7). Table 1 Genant-modif Sharp scores Change from BL at Yr 1 (DB)* Change from BL at Yr 2 (LTE)† Change at Yr 2 (Yr 1 as BL)‡ Aba + MTX Pbo + MTX Aba/Aba + MTX Pbo/Aba + MTX Aba/Aba + MTX Pbo/Aba + MTX n=376§ n=160§ n=376§ n=160§ n=376§ n=160§ ES, mean (SD) 0.62 (1.82) 1.44 (3.11) 0.84 (2.05) 1.69 (3.44) 0.21 (1.06) 0.25 (1.72) ES, median 0.00 0.00 0.00 0.26 0.00 0.00 (25%, 75%) (0.00, 0.77) (0.00, 1.57) (0.00, 1.28) (0.00, 2.08) (0.00, 0.26) (0.00, 0.51) JSN, mean (SD) 0.45 (1.48) 0.95 (2.46) 0.71 (2.12) 1.48 (3.90) 0.24 (1.19) 0.51 (1.74) JSN, median 0.00 0.00 0.00 0.00 0.00 0.00 (25%, 75%) (0.00, 0.24) (0.00, 0.94) (0.00, 0.48) (0.00, 1.40) (0.00, 0.00) (0.00, 0.00) TS, mean (SD) 1.07 (2.86) 2.40 (5.14) 1.55 (3.65) 3.17 (6.96) 0.46 (1.96) 0.75 (3.17) TS, median 0.00 0.46 0.00 0.51 0.00 0.00 (25%, 75%)} (0.00, 1.26) (0.00, 2.63) (0.00, 2.02) (0.00, 3.90) (0.00, 0.48) (0.00, 0.78) *All patients who entered LTE; † All received a fixed dose of Aba ∼10 mg/kg in the LTE; ‡ All patients who entered the LTE and had radiographs at Day 365 and Day 729; § Patients from 1 site were excluded due to compliance issues.Conclusion: In AIM, 2 yrs of Aba treatment slowed progression of structural damage in RA patients with an inadequate response to MTX. The effect seen at Yr 2 was significantly better than that seen at Yr 1.References: Genant et al. Ann Rheum Dis 2005;64(Suppl III):56Citation: Ann Rheum Dis, volume 65, supplement II, year 2006, page 57Session: RA – treatment biologics