ABSTRACT Rheumatoid arthritis (RA), the most common rheumatic disease, affects 1.5 million people in the United States and can lead to debilitating joint pain, functional limitations, and premature mortality. Existing treatment approaches based on immunosuppressive medications reduce disease severity but often fail to adequately control symptoms and can lead to severe adverse side effects. This proposal addresses the critical unmet need for non-pharmacologic strategies to augment medical management of RA, improve long-term clinical outcomes, and reduce disease-related symptoms. Psychological stress is postulated to exacerbate disease severity in autoimmune diseases, but few studies have prospectively examined its impact on disease activity in RA patients or the therapeutic potential of interventions that improve stress resilience in this patient group. Furthermore, while mindfulness-based interventions (MBIs), including the mindfulness-based stress reduction program (MBSR), have been shown to reduce psychological stress and pain in several chronic diseases, it remains unknown whether they represent an effective adjunctive approach for improving disease outcomes in RA. To address these significant knowledge gaps, I propose to examine the effects of stress, stress-buffering factors, and MBIs on risk of disease flares and symptom severity in RA and related autoimmune conditions. I will first identify mechanistic targets for mind-body interventions in RA by building on an actively enrolling RO1-funded longitudinal cohort study of RA patients. Aim 1 will determine whether greater negative psychological stress independently associates with increased risk of worse RA disease activity and symptom severity over time. I will further test whether stress resilience and mindfulness longitudinally correlate with better outcomes—including less severe disease activity and symptoms—to identify key targets for non-pharmacologic interventions in this patient group. In Aim 2 I will develop augmentations to the mindfulness-based stress reduction (MBSR) course for people with inflammatory arthritis, and conduct a pilot study to assess the feasibility and acceptability of an MBSR trial for improving disease outcomes in RA. This will be the first longitudinal study to examine the effects of psychological stress and stress resilience on RA disease activity. Further, this study will advance the field of integrative rheumatology by developing innovate methods to augment MBSR for people with immune-mediated inflammatory diseases. The proposed study will generate proof-of-concept data to inform a subsequent randomized controlled trial with R-level funding to test whether MBSR improves RA disease activity and symptoms. Importantly, this K23 Career Development Award will catalyze my successful transition to an independent physician-scientist with an impactful research program defining mechanisms and efficacy of MBIs in people with rheumatic conditions.