Patient and Caregiver Health State Utilities in Lennox-Gastaut Syndrome and Dravet Syndrome

Lo, Siu Hing; Lloyd, Andrew; Marshall, J.D.; Vyas, Kishan

doi:10.1016/j.clinthera.2021.09.017

Cited by 8 publications

(13 citation statements)

References 36 publications

(22 reference statements)

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“…The results showed that the number of seizure free days (SFD) within a 28-day period had a significant impact on quality of life (QoL). This study provides quantitative evidence to support previous research indicating the positive impact of seizure free days on the QoL of both patients with DS and their carers (8,17,33). Age and comorbidities also affect patient QoL, supporting findings found in previous studies (34).…”

Section: Discussionsupporting

confidence: 89%

“…Previous studies that have explored the nature and impact of seizures in DS have focused on measurement of seizure frequency, or self-rated seizure severity, and used that to calculate the effect on QoL (15)(16)(17). However, a recent study (33) showed that DS impacts patients and carers beyond seizures, and highlighted the need for future clinical trials to fully explore the value of therapeutic interventions beyond simple seizure frequency reduction.…”

Section: Discussionmentioning

confidence: 99%

“…However, the magnitude of this relationship was not quantified (15,16), and there was a paucity of research exploring whether short-term periods of seizure freedom (rather than longer-term remission) or complete seizure freedom (rarely obtained in DS), may be an important and meaningful metric in quantifying the burden of illness. To help address this gap, a recent study with DS expert clinicians was conducted (17), and confirmed that a convulsive seizure-free day (SFD) was directly relevant to patients' and carer's QoL. Increasing the number of convulsive SFDs is therefore also expected to reduce the physical burden, anxiety and fears experienced by caregivers, and improve their QoL.…”

Section: Introductionmentioning

confidence: 99%

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Determining the Relationship between Seizure-Free Days and Other Predictors of Quality of Life in Patients with Dravet Syndrome and Their Carers

Pinsent

Weston

Adams

et al. 2022

Preprint

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Objectives: Dravet syndrome (DS) is a rare, lifelong epileptic encephalopathy characterised by frequent and severe seizures associated with premature mortality. Typically diagnosed in infancy, patients also experience progressive behavioural, motor-function and cognitive decline. Twenty percent of patients do not reach adulthood. Quality of life (QoL) is impaired for both patients and their carers. Reducing convulsive seizure frequency, increasing seizure free days (SFDs) and improving patient/carer QoL are primary treatment goals in DS. This study explored the relationship between SFDs and patients' and carers' QoL to inform a cost-utility analysis of fenfluramine. Methods: In fenfluramine registration studies, patients (or their carer proxies) completed the Paediatric Quality of Life inventory (PedsQOL). These data were mapped to EuroQol-5 Dimensions Youth version (EQ-5D-Y) to provide patient utilities. Carer utilities were collected using EQ-5D-5L and mapped to EQ-5D-3L to align patient and carer QoL on the same scale. Linear mixed-effects and panel regression models were tested and Hausman tests identified the most appropriate approach for each group. On this basis, a linear mixed-effects regression model was used to examine the relationships between patient EQ-5D-Y, and clinically relevant variables (age, frequency of SFDs per 28-days, motor impairments and treatment dose). A linear panel regression model examined the relationship between SFDs and carer QoL. Results: Adjusting for age and underlying comorbidities, the patient regression model showed that SFDs per 28-days was a significant predictor of QoL. Each additional patient-SFD increased utility by 0.005 (p<.001). The carer linear panel model also showed that increasing SFDs per 28-days was a significant predictor of improved QoL. Each additional SFD increased carer utility by 0.014 (p<.001). Significance: This regression framework highlights that SFDs are significantly correlated with both patients' and carers' QoL. Treatment with effective antiseizure medications that increase SFDs, directly improves QoL for patients and their carers.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Determining the Relationship between Seizure-Free Days and Other Predictors of Quality of Life in Patients with Dravet Syndrome and Their Carers

Pinsent

Weston

Adams

et al. 2022

Preprint

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“…The potential of treatment to result in additional seizure‐free days is also not captured by evaluation of reductions in seizure frequency. The occurrence of additional seizure‐free days has been shown to improve both patient and caregiver QoL and may have a greater impact on patient QoL than seizure reductions 14,15 . Considering the above, the number of days without seizures is regarded by some experts as a more meaningful indication of the actual everyday benefits of a treatment than endpoints focusing on seizure frequency 5,8,10 .…”

Section: Introductionmentioning

confidence: 99%

Seizure‐free days as a novel outcome in patients with Lennox–Gastaut syndrome: Post hoc analysis of patients receiving cannabidiol in two randomized controlled trials

Auvin

Nortvedt²,

Fuller

et al. 2023

Epilepsia

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Objective: In this post hoc analysis, we aimed to assess seizure-free days as a potential new outcome measure to use in randomized placebo-controlled trials (RCTs) of patients with Lennox-Gastaut syndrome (LGS). Methods:In two phase 3 RCTs (GWPCARE3, GWPCARE4), eligible patients were randomized to receive plant-derived highly purified cannabidiol (CBD; Epidiolex® in the USA; 100 mg/mL oral solution) at 10 mg/kg/day (CBD10; GWPCARE3 only), at 20 mg/kg/day (CBD20), or matched placebo. The treatment period comprised a 2-week dose titration and a 12-week maintenance period. This post hoc analysis evaluated the least-squares (LS) mean changes from baseline and difference versus placebo in the number of drop or total seizure-free days per 28 days during the treatment period or maintenance period alone. LS mean changes were estimated using an analysis of covariance model, with categorical age and baseline number of drop or total seizure-free days as covariates, and treatment group as a fixed factor.Results: A total of 396 patients were included in this post hoc analysis. During the 14-week treatment period, LS mean changes from baseline in number of drop seizure-free days per 28 days for patients receiving placebo (n = 161), CBD10 (n = 73), and CBD20 (n = 162) were 2.81 (95% confidence interval [CI] = 1.75-3.88), 5.64 (95% CI = 4.08-7.20), and 6.45 (95% CI = 5.39-7.52), respectively. The LS mean differences in number of drop seizure-free days versus placebo were 2.83 (95% CI = .98-4.68) for CBD10 and 3.64 (95% CI = 2.18-5.10) for CBD20. For total seizure-free days, LS mean differences versus placebo were 2.63 (95% CI = .92-4.34) for CBD10 and 3.50 (95% CI = 2.16-4.85) for CBD20. The improvements from baseline in seizure-free days during the maintenance period alone were similar to the entire treatment period.Significance: Drop and total seizure-free days represent potential new and clinically meaningful endpoints for future RCTs in patients with LGS.

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“…Dravet syndrome (DS) is a treatment-resistant, developmental, and genetic form of epileptic encephalopathy ( Mei et al, 2019 ; Lo et al, 2021 ). The main features of DS include an early onset, various forms of seizures, delayed psychomotor development, and drug resistance ( Dravet, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of adjunctive antiseizure medications for dravet syndrome: A systematic review and network meta-analysis

Zhang

et al. 2022

Front. Pharmacol.

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Purpose: Recently, the U.S. Food and Drug Administration (FDA) approved stiripentol, cannabidiol, and fenfluramine to treat patients with Dravet syndrome (DS). Moreover, soticlestat was determined as a promising new drug for the treatment of DS as it has good efficacy and safety. However, the efficacy and safety of these drugs have not yet been evaluated in “head-to-head” trials. This study aimed to compare and evaluate the efficacy and safety of these adjunctive antiseizure medications in the treatment of DS.Methods: We searched in PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs) and open-label extension (OLE) studies in patients with DS. We performed a random-effect meta-analysis of OLE studies and a network meta-analysis for RCTs to evaluate the efficacy and safety of antiseizure medications in the treatment of DS. Primary efficacy outcomes were defined as a ≥50% reduction in seizure frequency compared with baseline. Furthermore, safety evaluation indicators were defined as the incidence of adverse events (AEs) and serious adverse events (SAEs) during treatment. Relative ranking was assessed using the surface under the cumulative ranking curve (SUCRA) probabilities.Results: Seven RCTs involving four antiseizure medications (stiripentol, cannabidiol, fenfluramine, and soticlestat) and a total of 634 patients were included in the analysis. According to the SUCRA results, all four drugs significantly reduced the frequency of seizures compared with the placebo. Soticlestat was the most likely to reduce seizure frequency by ≥50% compared to the baseline [risk ratio (RR): 19.32; 95% confidence interval (CI): 1.20–311.40], followed by stiripentol and fenfluramine. Stiripentol was ranked highest for the near percentage reduction in the seizure rate from baseline [RR: 12.33; 95% CI: 1.71–89.17] and the occurrence of any treatment-emergent adverse events [RR: 3.73; 95% CI: 1.65–8.43] and serious adverse events [RR: 4.76; 95% CI: 0.61–37.28]. A total of ten OLE studies containing 1,121 patients were included in our study. According to the results of the meta-analysis, the order of probability of reducing seizure frequency by ≥50% was fenfluramine (0.715, 95% CI: 0.621–0.808), stiripentol (0.604, 95% CI: 0.502–0.706), cannabidiol (0.448, 95% CI: 0.403–0.493). And the probability of occurrence of AEs is ranked as fenfluramine(0.832, 95% CI: 0.795–0.869), cannabidiol (0.825, 95% CI:0.701–0.950), stiripentol (0.823, 95% CI: 0.707–0.938), soticlestat (0.688, 95% CI: 0.413–0.890).Conclusion: According to the results of indirect comparison of efficacy and safety, cannabidiol is slightly inferior to the other three antiseizure medications in terms of efficacy and safety. Soticlestat, fenfluramine, and stripentol may have little difference in efficacy, but soticlestat and fenfluramine are safer. Soticlestat is probably the best adjunctive antiseizure medication, followed by fenfluramine. This conclusion is consistent with the comparison of long-term efficacy and safety.

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Patient and Caregiver Health State Utilities in Lennox-Gastaut Syndrome and Dravet Syndrome

Cited by 8 publications

References 36 publications

Determining the Relationship between Seizure-Free Days and Other Predictors of Quality of Life in Patients with Dravet Syndrome and Their Carers

Determining the Relationship between Seizure-Free Days and Other Predictors of Quality of Life in Patients with Dravet Syndrome and Their Carers

Seizure‐free days as a novel outcome in patients with Lennox–Gastaut syndrome: Post hoc analysis of patients receiving cannabidiol in two randomized controlled trials

Efficacy and safety of adjunctive antiseizure medications for dravet syndrome: A systematic review and network meta-analysis

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