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

Simona Balestrini; Viola Doccini; Alessandra Boncristiano; Matteo Lenge; Salvatore De Masi; Renzo Guerrini

doi:10.1007/s40801-022-00305-7

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

Drugs Real World Outcomes. 2022 Sep;9(3):451-461. doi: 10.1007/s40801-022-00305-7. Epub 2022 Jun 9.

Authors

Simona Balestrini^{1

2

3}, Viola Doccini¹, Alessandra Boncristiano¹, Matteo Lenge¹, Salvatore De Masi⁴, Renzo Guerrini⁵

Affiliations

¹ Neuroscience Department, Meyer Children's Hospital-University of Florence, Viale Pieraccini 24, 50139, Florence, Italy.
² Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
³ Chalfont Centre for Epilepsy, Buckinghamshire, UK.
⁴ Clinical Trial Office, Meyer Children's University Hospital, Florence, Italy.
⁵ Neuroscience Department, Meyer Children's Hospital-University of Florence, Viale Pieraccini 24, 50139, Florence, Italy. r.guerrini@meyer.it.

Abstract

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.