ABATACEPT PROVIDES SIGNIFICANT AND SUSTAINED BENEFITS IN CLINICAL AND PATIENT-REPORTED OUTCOMES THROUGH 2 YRS IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA) AND AN INADEQUATE RESPONSE TO METHOTREXATE (MTX): THE LONG-TERM EXTENSION (LTE) OF THE AIM TRIAL

Background: RA therapies should provide sustained benefits in clinical and patient-reported outcomes (PRO). In AIM (Abatacept [Aba] in Inadequate responders to MTX), Aba + MTX has been shown to provide significant benefits in clinical outcomes and PRO.Objectives: Clinical benefits and PRO were examined during the 1-yr, double-blind (DB) phase and the open-label LTE phase of the Phase III AIM trial.Methods: Patients were treated with a fixed dose of Aba (∼10 mg/kg) or placebo (Pbo) on Days 1, 15, 29, and every 4 weeks thereafter, plus MTX for 1 yr. Patients who completed the DB phase were eligible to enter the LTE, during which all patients were treated with a fixed dose of Aba ∼10 mg/kg every 4 weeks. Clinical outcomes were measured using ACR 20, 50 and 70 scores and the Disease Activity Score 28 (DAS28). PRO were assessed using the physical and mental component summary scores (MCS and PCS, respectively) of the Short Form (SF)-36, and the Health Assessment Questionnaire Disability Index (HAQ-DI) was used to assess physical function.Results: A total of 433 vs 219 patients were randomized and treated with Aba vs Pbo, with 385 (88.9%) vs 162 (74.0%) completing 1 yr. 539 patients entered the LTE. Discontinuation rates during the LTE were low (9.5%, n=51). ACR 20, 50 and 70 responses were maintained through 2 yrs with Aba treatment (Yr 1 vs Yr 2: ACR 20=82 vs 80%, ACR 50=54 vs 56%, ACR 70=32 vs 34%; Table). Patients that switched to Aba at the start of the LTE achieved similar ACR responses following 1 yr of treatment compared with those receiving Aba from Day 1 (ACR 20=78%, ACR 50=58%, ACR 70=32%). Rates of DAS28-defined remission (DAS28 <2.6) and HAQ-DI responses were similar at 1 yr of LTE, regardless of initial randomization. Significant improvements in the SF-36 PCS and MCS were seen with Aba vs Pbo at the end of the DB phase [1]; benefits were sustained during the LTE. Safety results will be presented separately. AIM Yr 1 (DB)* AIM Yr 2 (LTE)*† Aba+MTX Pbo+MTX Aba/Aba+MTX Pbo/Aba+MTX (n=376) (n=160) (n=376) (n=160) ACR 20, n (%) 308 (81.9) 86 (53.8) 302 (80.3) 125 (78.1) ACR 50, n (%) 203 (54.0) 40 (25.0) 209 (55.6) 93 (58.1) ACR 70, n (%) 122 (32.4) 14 (8.8) 129 (34.3) 51 (31.9) Remission (DAS28<2.6), n(%) 94 (25.4) 4 (2.5) 102 (30.9) 47 (32.6) PCS, mean change from baseline (SD) 9.70 (0.50) 6.61 (0.74) 10.63 (0.54) 10.52 (0.85) MCS, mean change from baseline (SD) 7.29 (0.60) 6.41 (0.85) 7.23 (0.61) 8.26 (1.00) HAQ-DI responders‡, n (%) 270 (71.8) 86 (53.8) 251(66.8) 101 (63.1) *All patients who entered the LTE (excluding 2 in the Aba arm and 1 in the Pbo arm due to study compliance issues at 1 site); missing observations after discontinuation were considered non-responses; † All patients received a fixed dose of Aba ∼10 mg/kg in the LTE; ‡ Improvement of 0.3 units from baseline.Conclusion: In AIM, Aba provided sustained clinical and PRO benefits through 2 yrs in patients with active RA and an inadequate response to MTX.References: 1. Kremer et al. ACR Annual Meeting; 16-21 October 2004:L2Citation: Ann Rheum Dis, volume 65, supplement II, year 2006, page 327Session: Rheumatic arthritis – treatment biologics