Understanding the health economic burden of patients with tuberous sclerosis complex (TSC) with epilepsy: a retrospective cohort study in the UK Clinical Practice Research Datalink (CPRD)

Abstract

IntroductionEpilepsy is highly prevalent in tuberous sclerosis complex (TSC), a multi-system genetic disorder. The clinical and economic burden of this condition is expected to be substantial due to treatment challenges, debilitating co-morbidities and the relationship between TSC-related manifestations. This study estimated healthcare resource utilisation (HCRU) and costs for patients with TSC with epilepsy (TSC+E) in the UK.MethodsPatients with TSC+E in the Clinical Practice Research Datalink (CPRD) linked to Hospital Episodes Statistics were identified from April 1997 to March 2012. Clinical data were extracted over the entire history, and costs were reported over the most recent 3-year period. HCRU was compared with a matched Comparator cohort, and the key cost drivers were identified by regression modelling.ResultsIn total, 209 patients with TSC+E were identified, of which 40% recorded ≥2 other primary organ system manifestations and 42% had learning disability. Treatment with ≥2 concomitant antiepileptic drugs (AEDs) was prevalent (60%), potentially suggesting refractory epilepsy. Notwithstanding, many patients with TSC+E (12%) had no record of AED use in their entire history, which may indicate undertreatment for these patients.Brain surgery was recorded in 12% of patients. Routine electroencephalography and MRI were infrequently performed (30% of patients), yet general practitioner visits, hospitalisations and outpatient visits were more frequent in patients with TSC+E than the Comparator. This translated to threefold higher clinical costs (£14 335 vs £4448), which significantly increased with each additional primary manifestation (p<0.0001).ConclusionsPatients with TSC+E have increased HCRU compared with the general CPRD population, likely related to manifestations in several organ systems, substantial cognitive impairment and severe epilepsy, which is challenging to treat and may be intractable. Disease surveillance and testing appears to be inadequate with few treatments trialled.Multidisciplinary care in TSC clinics with specialist neurologist input may alleviate some of the morbidity of patients, but more innovative treatment and management options should be sought.

A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)

“…These different manifestations are grouped under the term "TSCassociated neuropsychiatric disorders" (TAND). Data from the TOSCA registry [21] revealed that 54.9% of persons with TSC had some level of intellectual disability (50 to 65% in prior studies [1,23,[35][36][37]), with good agreement present between caregiver-reported and psychometric Table 1 Prevalence of common clinical manifestations in TSC patients (Continued)…”

“…Subependymal giant cell astrocytomas (SEGAs) were found in 24.4% of the TOSCA population. SEGA can obstruct the intraventricular space and lead to noncommunicating hydrocephalus requiring surgery (22.4% of those [20][21][22][23][24][25] The prevalence rate (32.9%, 35.9%) of pharmacoresistant epilepsy is similar to general population with focal epilepsy [26,27]. A mutation in the TSC2 gene is a risk factor for infantile spasms (47.3% vs. 23% with TSC1 in TOSCA) as well as an earlier manifestation of epilepsy, a higher seizure frequency, and pharmacological refractoriness [28].…”

“…Intellectual disability 53.6-65% [1,23,[35][36][37] Joinson et al [38] described a bimodal distribution of intellectual impairment in TSC. About two-thirds of the studied individuals had an intelligence quotient (IQ) in the normal range, albeit with an overall negative shift (mean IQ: 93), while 31% had a profound intellectual disability [38].…”

“…Autism 25-61% [21,23,24,40,[42][43][44][45][46][47] Intellectual impairment and the presence of infantile spasms are associated with higher risks for both autism and ADHD [36,48].…”

A Review of Investigations for Patients With Tuberous Sclerosis Complex Who Were Referred to the Tuberous Sclerosis Clinic at The Hospital for Sick Children: Identifying Gaps in Surveillance

“…As such, the care of TSC is associated with increased health care resource utilization as well as costs and the condition itself has profound impacts on quality of life. [12][13][14][15] Given the recent development of a comprehensive TSC clinic at our center, we aimed to better understand the care delivered to children with TSC before being seen in our TSC clinic to determine which gaps in surveillance of TSC care existed by examining whether the 2012 Tuberous Sclerosis Complex Consensus Recommendations were being followed. Of note, a revision to TSC guidelines is anticipated in the near future.…”