Claims Analysis Highlights Sleep Apnea Comorbidity as Risk Factor for Increased Mortality in Youths With Epilepsy

A claims database analysis featuring over 2 million patient-years (PY) and nearly 1 million unique patients revealed that sleep apnea comorbidity may be associated with an increased mortality in children and young adults with severe epilepsy. Despite the study’s limitations, the findings warrant further research to inform clinical practice, while emphasizing the need to raise awareness of the elevated risk associated with sleep apnea comorbidities in this patient population.¹

Presented at the 2024 American Epilepsy Society (AES) Annual Meeting, held December 6-10 in Los Angeles, California, the study featured 968,993 unique patients with severe epilepsy identified within the KOMODO US claims database. Coming into the study, these patients had 2 or more of either an epilepsy-related emergency department visit or hospital admission, status epilepticus diagnosis, or generalized tonic-clonic seizures.

Led by Stefanie Dedeurwaerdere, PhD, MBA, Innovation and Value Creation Lead at UCB, the study classified patients using ICD-10 codes into groups with central sleep apnea (CSA; 15,486 PYs) or other sleep apnea (OSA, including obstructive apnea; 313,024 PYs). Comorbidities were identified using the Charlson Comorbidity index, and each patient-year by age group was linked to an all-cause mortality probability based on US general population data from the observation year. Death probabilities were compared with observed deaths in the claims data to calculate a standardized mortality ratio (SMR) for each group.

All told, results showed that children (ages 1-17) with CSA and severe epilepsy had an SMR of 135.9—considered a 35.9% higher rate than expected—and children with OSA and severe epilepsy had an SMR of 74.2. Children with severe epilepsy and other comorbidities had significantly elevated SMRs: 132.3 for congestive heart failure, 74.9 for hemiplegia/paraplegia, 55.3 for cerebrovascular disease, and 44.6 for chronic pulmonary disease, compared to 27.7 for severe epilepsy overall. Nearly half (46%) of patients with severe epilepsy and sleep apnea (CSA and OSA) used positive airway pressure treatments, such as CPAP or Bi-PAP, with SMRs decreasing with age in these groups.

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The link between sleep and epilepsy has been documented several times before; however, the specific connection between sleep apnea and mortality in those with severe epilepsy is less researched. Sleep comorbidities have been shown to impair autonomic function, increasing the likelihood of fatal cardiac and respiratory events in individuals with epilepsy. For example, OSA has been shown to cause nocturnal hypoxemia, which may trigger seizures and elevate mortality risk.

A notable 2014 study showed that positive airway pressure therapy may produce beneficial effects on seizures and adults with epilepsy and OSA. Among 132 participants with epilepsy, 76 (57.6%) had OSA, with 43 (56.6%) on PAP therapy—83.7% of whom were adherent (≥4 hours/night, ≥5 nights/week)—and 33 (43.4%) not receiving therapy due to intolerance or refusal. In the study, results revealed a significantly greater percentage of patients with at least a 50% seizure reduction and a larger mean percentage of seizure reduction who were on PAP (73.9%; 58.5%) than those with untreated OSA (14.3%; 17.0%).²

Additional data from the study showed 83.7% of the PAP-treated group achieved successful outcomes (≥50% seizure reduction or seizure-free), outperforming the no-OSA (53.6%) and untreated OSA (39.4%) groups. After adjusting for confounding factors, the odds of successful outcomes were 9.9 times higher in the PAP-treated group compared with untreated OSA and 3.91 times higher than in the no-OSA group. Notably, the odds of achieving at least a 50% seizure reduction were 23.3 times greater compared with untreated OSA and 6.13 times greater than no OSA.

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REFERENCES
1. Dedeurwaerdere S, Lloyd D, Davis A, et al. Sleep Apnea Is Associated with High Mortality Risk in Children with Severe Epilepsies: An Observational Analysis from Large Scale US Claims Data. Presented at: 2024 AES Annual Meeting; December 6-10; Los Angeles, CA. ABSTRACT 1.51.
2. Pornsiriniyom D, Kim H, Bena J, Andrews ND, Moul D, Foldvary-Schaefer N. Effect of positive airway pressure therapy on seizure control in patients with epilepsy and obstructive sleep apnea. 2014;37:270-275. doi:10.1016/j.yebeh.2014.07.005