Stiripentol in the treatment of adults with focal epilepsy- a retrospective analysis

Habermehl, Lena; Mross, Peter; Krause, Kristina; Immisch, Ilka; Chiru, Daniela; Zahnert, Felix; Gorny, Iris; Strzelczyk, Adam; Rosenow, Felix; Möller, Leona; Menzler, Katja; Knake, Susanne

doi:10.1016/j.seizure.2021.03.019

Cited by 8 publications

(5 citation statements)

References 18 publications

(23 reference statements)

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“…The presented results are in line with the majority of previous studies published on STP use in DS [4, 5, 8-10, 13, 15-20] and other epilepsy syndromes [13,16,[21][22][23]. Previous publications reported a wide range for responder rates, defined as a >50% seizure reduction, from 23% [9] to 84% [16] for all seizure types in DS.…”

Section: Discussionsupporting

confidence: 91%

“…However, the initiation of STP in adulthood was also associated with a sustained higher response over time than initiation in age 5–18 years. The long-term efficacy of STP when initiated in adulthood in any epilepsy syndromes is a novel finding, as previous evidence of later initiation was only reported in two small cohorts with DS [ 9 ] and focal epilepsies [ 22 ], with evidence of lower responder rates. The evidence for efficacy of STP when initiated in adulthood has important implications also for regulatory reasons, as for example in the UK this drug does not have a marketing authorisation for initiation in patients with DS >18 years of age.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Long-Term Treatment with Stiripentol in Children and Adults with Drug-Resistant Epilepsies: A Retrospective Cohort Study of 196 Patients

Balestrini

Doccini

Boncristiano

et al. 2022

Drugs - Real World Outcomes

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Background Stiripentol is an antiseizure medication with multiple potential mechanisms of action, indicated as adjunctive therapy in people with Dravet syndrome, whose seizures are not adequately controlled with clobazam and valproate. However, there are scattered data on its efficacy in other epilepsy aetiologies and types. We previously reported our single-centre experience on the efficacy of adjunctive stiripentol treatment in a cohort of 132 patients with different types of refractory epilepsies. Objective We aimed to expand our analysis to a larger cohort of 196 patients with a long-term follow-up. Methods We retrospectively evaluated long-term efficacy, tolerability and predictors of treatment response in 196 patients with a long-term follow-up (range 0.5–232.8 months). Results After an initial median follow-up of 3 months after stiripentol introduction, we observed a responder rate of 53% including seizure freedom in 9%. At subsequent follow-ups at 12 and 24 months, responder rates were 29% and 22%, respectively. Aetiology was associated with sustained response over time, with Dravet syndrome being the aetiology with the highest responder rate (64%) at 48 months compared with syndromes with other genetic causes (13%) or unknown aetiology (38%). A higher responder rate over time was also observed in patients with generalised (44%) and combined focal and generalised epilepsies (28%) than in patients with focal epilepsies (20%). The highest relapse free-survival was observed when stiripentol was initiated at the youngest age (0–4 years) or in adulthood. The retention rate (i.e. proportion of patients who continued stiripentol with no change in either pharmacological or non-pharmacological therapy) was 53% at 12 months and 33% at 24 months. Conclusions Based on our findings, we suggest that stiripentol is an effective and well-tolerated therapeutic option not only in Dravet syndrome but also in other epilepsy syndromes with or without an established genetic aetiology. Response duration was influenced by age at stiripentol initiation across different aetiologies. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-022-00305-7.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Long-Term Treatment with Stiripentol in Children and Adults with Drug-Resistant Epilepsies: A Retrospective Cohort Study of 196 Patients

Balestrini

Doccini

Boncristiano

et al. 2022

Drugs - Real World Outcomes

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“…Since then, a post-marketing surveillance study in Japan involving data from 410 patients with DS (aged 0.5–50 years) reported responder rates of 43% for convulsive seizures, 55% for focal impaired awareness seizures, and 62% for generalised myoclonic seizures and/or generalised atypical absence seizures; the main AEs were somnolence (39%) and a loss of appetite (25%) [ 53 ]. A number of other observational studies have also confirmed the efficacy and safety of STP in real-world clinical practice across different age groups (including adults [ 54 ]) and with various follow-up periods, as recently reviewed [ 1 , 39 , 55 , 56 ]. However, studies also suggest that a significant proportion of patients may have inadequate seizure control over the long term, despite the use of this combination of ASMs [ 57 , 58 ].…”

Section: Stiripentol (Stp)mentioning

confidence: 95%

A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication

Strzelczyk

Schubert‐Bast

2022

CNS Drugs

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Dravet syndrome is a severe developmental and epileptic encephalopathy characterised by refractory seizures and cognitive dysfunction. The treatment is challenging, not least because the seizures are highly drug resistant, requiring multiple anti-seizure medications (ASMs), while some ASMs can exacerbate seizures. Initial treatments include the broad-spectrum ASMs valproate (VPA), and clobazam (CLB) in some regions; however, they are generally insufficient to control seizures. With this in mind, three adjunct ASMs have been approved specifically for the treatment of seizures in patients with Dravet syndrome: stiripentol (STP) in 2007 in the European Union and 2018 in the USA, cannabidiol (CBD) in 2018/2019 (in combination with CLB in the European Union) and fenfluramine (FFA) in 2020. These "add-on" therapies (mostly to VPA/ CLB) are used as escalation therapies, with the choice dependent on availability in different countries, patient characteristics and caregiver preferences. Topiramate is also frequently used, with evidence of efficacy in Dravet syndrome, and there is anecdotal evidence of efficacy with bromide, which is frequently used in Germany and Japan. With a growing treatment landscape for Dravet syndrome, there can be practical challenges for clinicians, particularly with issues associated with polypharmacy. This practical guide provides an overview of these main ASMs including their indications/contraindications, mechanism of action, efficacy, safety and tolerability profile, dosage requirements, and laboratory and clinical parameters to be evaluated. Standard laboratory and clinical parameters include blood counts, liver function tests, serum concentrations of ASMs, monitoring the growth of children, as well as weight loss and acceleration of behavioural problems. Regular cardiac monitoring is also important with FFA as it has previously been associated with cases of cardiac valve disease when used in adults at high doses (up to 120 mg/day) in combination with phentermine as a therapy for obesity. Importantly, no signs of heart valve disease have been documented to date at the low doses used in patients with developmental and epileptic encephalopathies. In addition, potential drug-drug interactions and their consequences are a key consideration in everyday practice. Interactions that potentially require dosage adjustments to alleviate adverse events include the following: STP + CLB resulting in increased plasma concentrations of CLB and its active metabolite norclobazam may increase somnolence, and an interaction with STP and VPA may increase gastrointestinal adverse events. Cannabidiol has a bi-directional interaction with CLB producing an increase in plasma concentrations of 7-OH-CBD and norclobazam resulting in the potential for increased somnolence and sedation. In addition, CBD is associated with elevations of liver transaminases particularly in patients taking concomitant VPA. The interaction between FFA and STP requires a dose reduction of FFA. Furthermore,

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“…Neutropenia has been reported in some cases and was reversible by dosage reduction [ 39 ]. Long-term efficacy and safety of stiripentol were later determined in several observational studies, including patients with a wide age range, including adults [ 40 , 41 , 42 , 43 ].…”

Section: Current Treatment Strategiesmentioning

confidence: 99%

Epilepsy in Dravet Syndrome—Current and Future Therapeutic Opportunities

Gao

Pielas

Jiao

et al. 2023

JCM

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Dravet Syndrome (DS) is a developmental epileptic encephalopathy characterized by drug-resistant seizures and other clinical features, including intellectual disability and behavioral, sleep, and gait problems. The pathogenesis is strongly connected to voltage-gated sodium channel dysfunction. The current consensus of seizure management in DS consists of a combination of conventional and recently approved drugs such as stiripentol, cannabidiol, and fenfluramine. Despite promising results in randomized clinical trials and extension studies, the prognosis of the developmental outcomes of patients with DS remains unfavorable. The article summarizes recent changes in the therapeutic approach to DS and discusses ongoing clinical research directions. Serotonergic agents under investigation show promising results and may replace less DS-specific medicines. The use of antisense nucleotides and gene therapy is focused not only on symptom relief but primarily addresses the underlying cause of the syndrome. Novel compounds, after expected safe and successful implementation in clinical practice, will open a new era for patients with DS. The main goal of causative treatment is to modify the natural course of the disease and provide the best neurodevelopmental outcome with minimum neurological deficit.

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Stiripentol in the treatment of adults with focal epilepsy- a retrospective analysis

Cited by 8 publications

References 18 publications

Efficacy and Safety of Long-Term Treatment with Stiripentol in Children and Adults with Drug-Resistant Epilepsies: A Retrospective Cohort Study of 196 Patients

Efficacy and Safety of Long-Term Treatment with Stiripentol in Children and Adults with Drug-Resistant Epilepsies: A Retrospective Cohort Study of 196 Patients

A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication

Epilepsy in Dravet Syndrome—Current and Future Therapeutic Opportunities

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