OBJECTIVES: Abatacept (CTLA4Ig) is the first in a new class of agents for the treatment of RA that selectively modulates the co-stimulatory signal required for full T-cell activation, has shown good and efficacy and tolerability during in a one-year, double-blind, placebo-controlled trial of Abatacept in methotrexate (MTX) inadequate responders. This analysis examined the long-term effect of Abatacept on patient-reported outcomes (PRO) in an open-label extension of this study at two-years. METHODS: In the blinded phase of the study, patients with active RA despite MTX treatment were randomized to receive Abatacept 10mg/kg IV monthly + MTX or placebo + MTX for one-year. Patients who completed the blinded phase were eligible to enroll in the long-term extension during which patients were treated with a fixed dose of Abatacept 10mg/kg. Patients evaluated pain and disease activity using the Visual Analog Scale (VAS), physical function using the modified Health Assessment Questionnaire (mHAQ), and QOL using the SF-36. RESULTS: In total, 115 patients were randomized to the Abatacept + MTX group; 84 patients (73%) entered the LTE and 75 (89%) of these patients completed two-years of treatment. Statistically significant improvements from baseline in pain, disease activity, and physical function were reported by Abatacept-treated patients as early as day 15, and were further improved and maintained during two-years of treatment. The improvements in patient reported outcomes preceded the improvement seen in the overall clinical response measured by the American College of Rheumatology criterion for a 50% improvement. Abatacept also sustained significant improvements in all eight domains of the SF-36, with the greatest improvements seen in physical function, role-physical, bodily pain, vitality and social function domains. CONCLUSIONS: Abatacept rapidly and significantly improves patient-reported outcomes and these improvements are sustained during two-years of treatment.