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Kempf, Graeme

University of British Columbia

Multiple sclerosis (MS) is an autoimmune disease that progresses over the course of years. MS is treated with disease-modifying drugs (DMDs). The efficacy of DMDs was established in clinical trials that were short and excluded older individuals and individuals living with comorbidities. This has led to a lack of knowledge of the effects of chronic DMD use and the effects of DMDs on individuals that do not meet the traditional eligibility criteria for clinical trials. This thesis applies multi-state models, which can advance the understanding of a disease beyond that offered by time-to-event models alone, to administrative healthcare data in a retrospective study to explore the long-term, real-world efficacy of DMDs. Chapter 2 applies time-to-event models and weighted cumulative exposure to explore the association between DMDs and mortality as well as to explore reverse causality. Chapters 3 and 4 implement an illness-death model to investigate the main research questions of this thesis: whether exposure to any DMD is associated with fewer hospitalizations, shorter hospitalizations, and/or a reduction in the chance of dying inside or outside the hospital. Specifically, in Chapter 3, Cox-type regressions estimate the hazard ratios (HRs) for exposure to any DMDs. In Chapter 4, pseudo-value regression models examine whether exposure is associated with more time spent alive and out of the hospital or more time hospitalized. Chapters 3 and 4 use interactions between DMD and comorbidity to analyze if the impact of DMDs changed across comorbidity burden. The change of the effects of exposure over time is also investigated in Chapters 2, 3, and 4. The results suggest that DMD use is initially associated with fewer hospitalizations but long-term DMD exposure is associated with more hospitalizations. Long-term DMD exposure is also associated with a greater hazard of dying outside the hospital. Pseudo-value regression suggested that exposure amongst individuals with high comorbidity burden is associated with more time spent alive and out of the hospital than it is for individuals with no comorbidity.

Text

2024-08-27

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89047

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University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/