Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Michael Rieder

Abstract

This integrated-article thesis explores the impact of long-term glucocorticoid (GC) therapy on children with RD. Long-term GC treatment is potentially associated with severe adverse drug reactions (ADRs). Our scoping review summarizes the current evidence health-related quality of life (HRQOL) impacts of this treatment on children with RD. We describe the frequency of ADRs related to long-term GC treatment in a convenience sample of pediatric RD patients on long-term prednisone therapy and evaluate clinical characteristics that may be associated with risk for of GC-related ADRs. Lastly, we present a pilot study to evaluate the feasibility of monitoring GC PK in children with RD in a prospective cohort with RD. We focus on prednisone, in particular, which is a synthetic GC used in high doses to manage moderate to severe inflammation in children with rheumatic diseases (RD). Our preliminary work demonstrates that patient factors such as baseline body-mass-index and PK variability may be associated with GC-related ADRs, which supports the need to refine our understanding of the dose-response relationship in GC treatment.

Summary for Lay Audience

Prednisone is a medication that is a synthetic glucocorticoid (GC) which has been associated with severe side effects, especially in children. Side effects may include weight gain, depression and anxiety, cataracts, diabetes, high blood pressure, weak bones, and growth problems. This work summarizes the burden of prednisone side effects in children with rheumatic diseases (RDs). First, we examined the impact of treatment with prednisone on health-related quality of life (HRQOL), by critically evaluating the current literature on this topic. We explored patient and disease related risk factors for children with RD treated with high-dose prednisone to develop side effects using a chart review of patients seen at a single academic pediatric rheumatology center. This thesis also explored the variability between the concentrations of GC in the blood after taking standardized weight-based doses, and the influence on drug concentration to the development of side effects. We conclude that patient factors such as concentrations of prednisolone in the blood and baseline body-mass-index (BMI) may contribute to a patient’s likelihood of developing side effects such as weight gain in children with RD. This work adds to the body of evidence that personalizing and adjusting doses of prednisone based on patient-specific factors (like blood concentrations) may reduce the risk of developing severe side effects to this treatment.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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