Abstract
Risk of death from suicide in Huntington's disease is notably elevated relative to that in the general population, although the incidence within HD populations has not been precisely defined. Robust incidence estimates of suicidal behavior can serve as references for HD therapeutic research and post-marketing surveillance to help evaluate the suicidality risk of novel therapeutics. To estimate the incidence rate of completed suicide and suicide attempt in the global, prospective HD cohort study Enroll-HD that records these events per protocol. A total of 20 912 participants were available for analysis (HD gene-expansion carriers (HDGECs) n = 15 924; non-HDGECs n = 4988) representing a collective observation period of 53 390 participant-years. Each observed event was subject to clinical review and evaluation. We generated incidence rates (events per 100 000 person-years) for suicides and suicide attempts using all available data, as well as by year of study and geographical region. Proportionate mortality statistics for suicide and respective 95% confidence intervals were also generated. The overall incidence rate of suicide in HDGECs was 72 per 100 000 person-years, and 8 per 100 000 person-years in non-HDGECs. Proportionate mortality attributable to suicide in HDGECs was 4.6%. For suicide attempts, the global overall incidence rate observed in HDGECs was 306-375 per 100 000 person-years, and 23-38 per 100 000 person-years in non-HDGECs. The incidence estimates calculated here can be used as a reference to help evaluate drug safety and may also be useful in assessing progress in clinical care for HDGECs once therapeutic interventions become widely available.
Highlights
Risk of death from suicide in Huntington’s disease is notably elevated relative to that in the general population, the incidence within HD populations has not been precisely defined
The global overall incidence rate observed in Huntington’s disease gene expansion carriers (HDGECs) was 306–375 per 100 000 person-years, and 23–38 per 100 000 person-years in non-HDGECs
The incidence estimates calculated here can be used as a reference to help evaluate drug safety and may be useful in assessing progress in clinical care for HDGECs once therapeutic interventions become widely available
Summary
Analyses were limited to generation of descriptive statistics. Incidence/event rate statistics were generated for suicide attempts and completed suicides, using all available data. Incidence statistics are presented by year of study and region. Proportionate mortality statistics and respective 95% confidence interval for suicide were generated. The 95% confidence interval estimation for the binomial proportions was based on the bootstrap percentile-t method as described by Mantalos and Zografos.[19] Strengthening the Reporting of Observational studies in Epidemiology guidelines were followed in reporting. All descriptive statistics are presented by gene status
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