Arijita Deb

Date of Graduation

2017

Document Type

Dissertation

Degree Type

PhD

College

School of Pharmacy

Department

Pharmaceutical Sciences

Committee Chair

Usha Sambamoorthi

Committee Co-Chair

Nilanjana Dwibedi

Committee Member

JoAnn Hornsby

Committee Member

Traci LeMasters

Committee Member

Usha Sambamoorthi

Committee Member

Wenhui Wei

Abstract

Depression is one of the most frequently occurring conditions in Rheumatoid Arthritis (RA) patients and understanding depression as a comorbidity in RA is very important. The link between RA and depression is very complex and influenced by a multitude of factors such as shared pathophysiologic pathways of inflammation, RA-related treatment response, as well as the patient's demographic and socio-economic factors, and general difficulties in coping with the disease. Depression can increase the clinical, humanistic, and economic burden among RA patients. Growing evidence now suggests that depression is a systemic inflammatory condition and may exert a negative influence on the treatment response in RA by its effect on pro-inflammatory cytokines. Therefore, it is important to understand how depression is related to the treatment effectiveness of specific cytokine inhibitor drugs such as Tumor Necrosis Factor Inhibitor (TNFi) therapy that are used for the treatment of RA. The powerful anti-inflammatory effect of TNFi may have a potential beneficial effect in reducing the risk of depression in RA patients. It is important to gain a comprehensive understanding of how depression affects RA and how RA can affect depression in real-world clinical practice settings, particularly among working-age individuals as the burden of depression is highest among working-age population. Therefore, this dissertation had three related aims focusing on working-age adults: 1) estimating the clinical, humanistic and economic burden of depression in RA; 2) examining the relationship between prevalent depression and treatment response to TNFi therapy in RA; and 3) evaluating the association between TNFi therapy and the risk of developing depression in RA. The study used data from multiple nationally representative sources to triangulate the complex relationship between RA and depression in working-age adults. These data sources were: the nationally representative Medical Expenditure Panel Survey (MEPS) for years 2009, 2011, 2013, and 2015 and a retrospective claims database for commercially insured working-age adults for the years 2009 through 2015. We found that one in every four working-age RA patients reported the presence of depression. RA patients with depression compared to RA patients without depression were significantly more likely to have pain-related interference with normal work, functional limitations, lower health-related quality of life (HRQoL) scores in the mental domain, higher annual healthcare expenditures and out-of-pocket spending burden, higher rate of unemployment, higher number of missed work days annually and higher lost annual wages due to missed work days. Depression was independently associated with treatment response to TNFi, even after adjusting for baseline predisposing, enabling, need and external environment factors among working-age RA patients. Among RA patients with depression, nearly three in every ten patients responded to TNFi therapy, whereas among RA patients without depression, nearly four in every ten patients responded to TNFi therapy. In addition, in a depression-free cohort of RA patients, those who responded to TNFi therapy were significantly less likely to develop newly-diagnosed depression as compared to those who did not respond to TNFi therapy. In summary, these findings underscore the importance of effectively managing depression in the routine clinical practice of RA patients to reduce pain, functional or activity limitations, improve quality of life, lower direct and indirect healthcare costs. In addition, the findings highlight the negative impact of depression on treatment response to TNFi and provide insights into specific subgroups of RA patients with depression who are at risk of responding poorly to TNFi. Furthermore, reduction in the risk of depression in TNFi responders suggests that TNFi therapy is important not only for clinical improvement in RA disease but also for reducing the risk of depression.

Download

Share

COinS