Lingyi (Gloria) Li
Doctor of Philosophy in Experimental Medicine (PhD)
The risk of multiple sclerosis among users of tumor necrosis factor inhibitors: A Canadian population-based study
The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.
BackgroundGranulomatosis with polyangiitis (GPA) is a form of ANCA-associated vasculitis (AAV), a heterogenous group of small vessel vasculitides associated with anti-neutrophil cytoplasmic antibodies (ANCA). There is still significant disease mortality despite advances in treatment of GPA. Furthermore, longitudinal data on secular trends in GPA mortality are scarce and most are from selected populations. We aim to determine all-cause and cause-specific mortality risks in GPA patients compared to the general population, as well as to estimate the difference in mortality risks in GPA patients between 1997-2004 and 2005-2012. MethodsChapter 2 was a systematic review and meta-analysis of observational studies in GPA. An extensive literature search was performed on the EMbase and Medline databases. Data was extracted for a pooled meta-analysis of standardized mortality ratios (SMR). Heterogeneity between studies was assessed using I2. Chapter 3 was a matched cohort population-based study using an administrative health database, comparing incident GPA cases and non-GPA individuals randomly selected from the general population. Primary outcome was death during the follow up period, 1997-2012. Cohorts were subdivided to early cohort (1997-2004) and late cohort (2005-2012). Hazard ratios (HR) were estimated using Cox proportional hazard regression models. ResultsFrom the meta-analysis, we found a 2.7-fold increased risk of death in AAV patients when compared to the general population. Subgroup analyses showed that mortality risks were higher in older cohorts with a trend towards improvement over time (i.e., midpoint of enrolment periods 1980-1993 and 1994-1999, vs. 2000-2005). From the matched cohort study, 370 GPA patients and 3,700 non-GPA individuals were included, with 68 and 310 observed deaths, respectively. Overall, the age, sex and entry time-adjusted all-cause mortality HR in the GPA cohort was 3.12 (95%CI 2.35-4.14). There was excess mortality from CVD causes, but not cancer, in the GPA cohort. All-cause mortality significantly improved between the early and late GPA cohorts (HR 5.61 vs. 2.33, respectively; p = 0.017).ConclusionThere was a 3-fold increase in all-cause mortality risks in GPA patients, with excess mortality from CVD causes. There was a significant improvement in all-cause mortality risks over time but remained elevated compared to the general population.
Background: Previous studies have shown that gout is an independent risk factor for cardiovascular diseases. Venous thromboembolism (VTE, including deep venous thrombosis [DVT] and pulmonary embolism [PE]) represents the third most common form of cardiovascular disease among the general population. However, data on the risk of VTE in gout patients are scarce. Objectives: 1) To estimate the overall risk of VTE, DVT, and PE before and after gout diagnosis in an incident cohort of individuals with gout; 2) To access the temporal trend of VTE, DVT, and PE before and after gout diagnosis compared with the general population.Methods: I conducted a 1:1 matched cohort study using a province-wide population-based administrative health database from British Columbia, Canada. I calculated incidence rate ratios and multivariable adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the risk of VTE, DVT, and PE before and after gout diagnosis. Results: Among 124,306 individuals with newly diagnosed gout (65% male, mean age 60 years), VTE developed in 1,594 patients, DVT in 989 patients, and PE in 813 patients. Incidence rates were 2.44, 1.51, and 1.24 per 1,000 person-years, respectively. The corresponding incidence rates among non-gout individuals were 1.37, 0.83, and 0.75 per 1,000 person-years, respectively. The final aHRs (95% CI) for VTE, DVT, and PE were 1.34 (1.23-1.46), 1.38 (1.24-1.54), and 1.27 (1.13-1.42), respectively. For the entire pre-gout period, compared to general population, the final aHRs (95% CI) were 1.56 (1.41-1.71), 1.55 (1.38-1.75) and 1.53 (1.34-1.76) for VTE, DVT and PE, respectively. During the 3rd, 2nd, and 1st years preceding the gout diagnosis, the final aHRs for VTE were 1.51, 1.61, and 1.74, respectively. During the 1st, 2nd, 3rd, 4th, and 5th years after the gout diagnosis, the final aHRs were 1.46, 1.44, 1.37, 1.36, and 1.32. Similar trends were also seen for DVT and PE. Conclusion: Increased risks of VTE, DVT, and PE were found both before and after gout diagnosis. The risk increased gradually before gout diagnosis, peaking in the year prior to gout diagnosis, and then progressively declined following the diagnosis. Gout associated inflammation may contribute to VTE risk.
Introduction: This thesis contains original analyses aimed at better understanding the burden of gout, an excruciatingly painful form of inflammatory arthritis, in the Canadian context. While gout is increasingly recognized as the most common form of inflammatory arthritis worldwide (e.g., reported prevalence of 3.9% and 2.5% in the United States and United Kingdom, respectively), no Canadian trend data are available. Objectives: 1) To evaluate the contemporary prevalence and incidence of gout over the past decade, as well as gout treatment patterns and comorbidity burden. 2) To evaluate the burden of hospitalized gout and corresponding inpatient costs as compared to rheumatoid arthritis (RA), another inflammatory joint disease known to incur substantial resource use. Methods: To address both objectives, I used PopulationData BC, a large administrative database spanning the province of British Columbia (BC). For Objective 1, I used physician and hospital visits to identify gout cases and estimate the annual trends in prevalence and incidence among the general population. I additionally used data from PharmaNet, BC’s prescription drug database, to examine gout treatment patterns (i.e., urate-lowering therapy, colchicine, glucocorticoids, and non-steroidal anti-inflammatory drugs) over the same time period. For Objective 2, I used hospital diagnoses and procedure codes to assess annual trends in hospitalizations and joint surgeries as well as inpatient costs for both gout and RA. Results: 1) Both the prevalence and incidence of gout have increased over the past decade (i.e., a 59% and 48% increase, respectively), while the prescription of gout treatment remains low. 2) The hospitalization rates for gout have doubled over the past decade, while those for RA have declined by 49%. The inpatient costs also reflected the hospitalization trends, with a 40% decrease in RA hospital costs, while gout costs more than doubled over the study period. Conclusion: Altogether, this thesis provides evidence that the burden of gout in Canada is substantial and increasing. These findings are further contrasted against the hospitalization burden of RA, which has decreased considerably over the same period. This thesis highlights the critical need to improve gout prevention and care to mitigate its rising disease burden in Canada and beyond.