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.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.