Date of Award

2017

Degree Type

Thesis

Degree Name

Master of Science in Pharmaceutical Sciences

Department

Biomedical and Pharmaceutical Sciences

First Advisor

Aisling Caffrey

Abstract

Background: Rheumatoid arthritis (RA) is an incurable autoimmune disease that can cause permanent joint damage and loss of function. Anti-tumor necrosis factor (anti-TNF) agents inhibit the function of tumor necrosis factor (TNF), which leads to a reduction in the progression of joint damage due to inflammation. However, an increased risk of serious infections in RA patients using anti-TNF agents has been observed in previous studies. This increased risk may be due to the immunologic disturbance of the RA disease process itself, the immunosuppressive properties of anti-rheumatic drug therapies, or co-existing risk factors for infection present in RA patients. Herein, our aim is to assess potential predictors of hospitalized infection in RA patients using anti-TNF agents.

Objective: Our objective is to determine if patients with RA who are prescribed the anti-TNF agents; adalimumab, etanercept, or infliximab, are at an increased risk of having a serious infection. In addition, we sought to identify potential predictors of an increased risk of infection in RA patients using anti-TNF agents.

Methods: A nested case-control study was conducted using de-identified data from the ClinformaticsTM DataMart (OptumInsight, Eden Prairie, MN), an administrative health claims database from a large national private insurer. An initial cohort of 78,657 patients with ≥1 RA diagnosis was identified. Patients were included from this initial cohort based on age, enrollment eligibility, number of RA diagnoses, exposure to an anti-TNF agent, and excluded based on certain comorbidities. A final RA cohort sample of 15,181 patients was formed. A follow-up period of 1 year was selected to analyze serious infections requiring hospitalization; these events were identified with a comprehensive set of ICD-9 codes for serious infections requiring inpatient admission. Patients were classified as cases if they experienced a serious infection during the 1-year follow up. The final selected cases and controls were matched on a 1:1 ratio based on gender, region, and RA cohort entry date (quarter, year). A total of 155 cases and 155 controls were identified. Both univariable and multivariable conditional logistic regression models were built to produce a final multivariable predictive model.

Results: Among, RA patients using anti-TNF agents, those with recent prednisone use were 1.873 times more likely to have a hospitalized infection (95% confidence interval [CI] 1.015-3.458). Patients with comorbid diabetes were 2.963 times more likely to experience a hospitalized infection (95% CI 1.445-6.078) and patients with comorbid chronic obstructive pulmonary disease (COPD) were 9.233 times more likely to experience a hospitalized infection (95% CI 2.755-30.947). Lastly, patients with a previous history of infection were 8.984 times more likely to have a hospitalized infection (95% CI 1.895-42.595). No associations between anti-TNF agent (adalimumab, infliximab, or etanercept) or incident/prevalent anti-TNF use and hospitalized infection were observed.

Conclusion: The use of specific anti-TNF agents was not independently associated with an increased risk of hospitalized infection in RA patients. Predictors associated with hospitalized infection in RA patients using anti-TNF agents included recent prednisone use, comorbid diabetes, comorbid COPD, and previous history of infection.

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