Prevalence, mortality and healthcare economic burden of tuberous sclerosis in Hong Kong: a population-based retrospective cohort study (1995–2018)

Abstract

Background We aim to elucidate the disease impact by accounting the prevalence, survival rate, genetics, mTOR inhibitor use and direct costs of tuberous sclerosis complex (TSC) in our local setting. TSC patients with documented visits to our local public hospitals in 1995–2018 were identified. The public hospitals captured most if not all local TSC patients. Demographics such as age, sex, death, genetic profiles were retrieved from the central electronic database. Data including prevalence, age distribution and survival rate were analysed. Direct cost was calculated with reference to the drug use and number of visits to various public hospital facilities. Results We identified 284 surviving TSC patients (55.3% male) in Hong Kong. The age range was from 4.5 months to 89.9 years, with a median age of 27.2 years. Paediatrics (< 18 years) to adult (≥18 years) ratio was 1:2.84. The overall prevalence of TSC patients was 3.87 in 100,000 (i.e. 1 in 25,833). Genetically, TSC1:TSC2 ratio is 1:2.7. Thirty seven patients died within the study period. The age of death ranged from 7.6 years to 77.8 years, with a median age of death at 36.6 years (IQR: 24.7–51.1 years). Most patients survived till adulthood. Survival rate at 20 and 50 years follow-up was 98.6 and 79.5% respectively. Two hundred and twenty nine TSC patients (71.3%) had neurological manifestations, sixteen patients (5.0%) had chronic kidney diseases and five patients (1.6%) had pulmonary lymphangioleiomyomatosis. Forty seven (16.5%) TSC patients were prescribed with mTOR inhibitors within the study period. Healthcare facility utilization was further analysed in the 2008–2018 cohort. In particular, the mean number of specialist out-patient clinic visits per patient-year was 9.23 per patient-year, which was 4.91 times more than that of local general population. Conclusions Prevalence of local TSC patients is within the range of that reported in the literature. Local TSC patients have fair long term survival, but they require disproportionally high healthcare cost when compared with the general population, particularly in terms of outpatient (OP) visits. Although effective disease-modifying agent (i.e. mTOR inhibitor) is available, it was not widely used yet in Hong Kong despite the fact that Government approved and supported its use recently. Further research on quality of life and setting up a comprehensive patient registry are necessary for more accurate assessment of cost and benefit.

Direct and indirect costs and cost-driving factors of Tuberous sclerosis complex in children, adolescents, and caregivers: a multicenter cohort study

“…The cost of mTOR inhibitor use is likely to decrease in the future as generic formulations become available, a phenomenon that has been well-demonstrated for other ASDs [ 25 , 46 ]. Although our study appears to agree with other COI studies regarding the contributions of hospitalization and ASD use [ 11 , 13 , 32 , 33 , 35 , 36 , 39 , 40 , 47 , 48 ] (for details, please refer to Table 7 ) performing direct comparisons against studies from different settings and different countries proved to be difficult, as the observed variations were likely associated with a variety of contributing factors including differences in definition, policy, measurements, and population (such as the combination of TSC/epilepsy cohorts). Furthermore, the resource use might change over time according to changes in organ manifestation during the lifetime of TSC patients [ 3 , 49 ].…”

Direct and indirect costs and cost-driving factors in adults with tuberous sclerosis complex: a multicenter cohort study and a review of the literature

“…In terms of the use of healthcare resources, our results appear to be in line with other COI studies, particularly hospitalization frequency and the use of ASDs [ 9 , 11 , 15 , 16 , 37 , 42 , 44 , 45 ]. Most studies could not evaluate mTOR inhibitor use because the periods of data inclusion preceded their authorization.…”

“…Most studies could not evaluate mTOR inhibitor use because the periods of data inclusion preceded their authorization. In our study, more patients (37%) used mTOR inhibitors than in three other recent studies (8–16.5%) [ 37 , 44 , 45 ].…”

“…To enable comparisons with other COI studies, we aimed to capture the most comprehensive set of cost items related to epilepsy and other TSC organ manifestations [ 4 , 39 ]. Previous studies have reported direct cost estimates for individuals with TSC in Europe [ 15 , 16 , 40 , 41 ], North America [ 9 , 11 , 37 , 38 , 42 – 44 ], and Asia [ 45 ], but none of these previous studies have provided indirect cost estimates for adults affected by TSC or examined the cost drivers of indirect and nursing care costs [ 4 ].…”

Efficacy, Retention and Tolerability of Everolimus in Patients with Tuberous Sclerosis Complex: A Survey-Based Study on Patients’ Perspectives

“…Tuberous sclerosis complex (TSC) is a rare genetic disorder with a prevalence of up to 1 in 5000 individuals that is caused by genetic variations in either the TSC1 or TSC2 gene, which result in the loss of function [1][2][3]. Both genes encode components of the hamartin-tuberin complex and serve as tumour suppressor genes by downregulating cell proliferation and differentiation via mechanistic target of rapamycin (mTOR) [4,5].…”