OBJECTIVE: Health-related quality of life (HRQOL) and the ability to function in daily activities are significantly impaired in patients with rheumatoid arthritis (RA). Improving physical function and well-being is an important treatment goal for RA. The effects of a biologic agent, abatacept, on patient HRQOL were examined in a Phase III trial, AIM (Abatacept in Inadequate responders to Methotrexate [MTX]). METHODS: AIM was a 1-year, double-blind, placebo-controlled trial evaluating a fixed dose of abatacept versus placebo on a background of methotrexate (MTX). Study drugs were given by monthly IV administration. A battery of pre-specified measures on multiple aspects of HRQOL were assessed: general quality of life including both physical and mental health by the SF-36, physical function by the Health Assessment Questionnaire (HAQ), and sleep quality by the Medical Outcomes Study Sleep Module (MOS-sleep), and fatigue by a 100 mm Visual Analog Scale. Analysis of covariance adjusting for baseline value was used to compare the treatment groups. RESULTS: In this study, 433 and 219 patients were treated with abatacept and placebo respectively. After 1 month of treatment, significant greater improvements from abatacept were observed in 5 out of 8 SF-36 subscales (bodily pain, role physical, general health, vitality, and social functioning) and fatigue compared to placebo. By 6 months, significant differences in favor of abatacept were seen in all HRQOL measures: physical function (HAQ), all 8 subscales of the SF-36, PCS and MCS, sleep quality, and fatigue. The improvements were deemed to be clinically meaningful using established criteria. The effects were sustained and further improved to the end of the study at 1 year. CONCLUSION: Abatacept demonstrated significant and consistent improvements in a broad range of HRQOL dimensions. These data suggest abatacept has the potential to provide real-life benefits to RA patients.