Prescription patterns of antiseizure drugs in tuberous sclerosis complex (TSC)-associated epilepsy: a multicenter cohort study from Germany and review of the literature

ABSTRACT

Objective

Seizures are a primary and early disease manifestation of Tuberous Sclerosis Complex (TSC). We aimed to describe the age-stratified patterns of antiseizure drug (ASD) treatments among children, adolescents, and adults with TSC in Germany. Additionally, we reviewed real-world and clinical study evidence regarding ASD utilization in patients with TSC.

Methods

We evaluated the pattern of routine ASD use and everolimus prescriptions based on a 2019 multicenter survey of 268 individuals with TSC-associated epilepsy. We contextualized the results with a structured review of real-world and clinical study evidence.

Results

TSC-associated epilepsy treatment comprises a wide variety of ASDs. In this German sample, the majority of patients were treated with polytherapy, and lamotrigine (34.7%), valproate (32.8%), oxcarbazepine (28.7%), vigabatrin (19.0%), and levetiracetam (17.9%) were identified as the most-commonly used ASDs. In addition, everolimus was used by 32.5% of patients. In adherence to current TSC guidelines, the disease-modifying ASD vigabatrin was widely used in children (58% below the age of 5 years), whereas treatment in adults did not necessarily reflect guideline preference for (partial) GABAergic ASDs.

Conclusions

The selection of ASDs for patients with TSC-associated epilepsy follows well-evaluated recommendations, including the guidelines regarding vigabatrin use in children. Several characteristics, such as the comparatively high frequency of valproate use and polytherapy, reflect the severity of TSC-associated epilepsy.

KEYWORDS:

• Epilepsy
• seizure
• antiepileptic drug
• vigabatrin
• mTOR inhibitor
• medication
• prescription pattern
• rare disease

Acknowledgments

The authors would like to thank all patients and caregivers who contributed to this survey and the German patient advocacy group Tuberöse Sklerose Deutschland e.V. for their help in recruiting participants.

Declaration of interest

AS reports personal fees and grants from Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceutical companies, LivaNova, Marinus Pharma, Medtronic, UCB, and Zogenix. TB reports personal fees from Eisai, Desitin Arzneimittel, GW Pharma, Novartis, Nutricia, Shire, Takeda, UCB Pharma and Zogenix. AB reports personal fees from Desitin Arzneimittel GmbH, Eisai GmbH, GW Pharma GmbH, Shire GmbH, UCB Pharma GmbH, and ViroPharma GmbH. II reports personal fees from UCB. JJ reports personal fees from Eisai, GW Pharmaceuticals companies, Zogenix and has been supported by the German Research Foundation (DFG; JA 1725/4-1). KAK reports personal fees from GW Pharmaceuticals companies and Zogenix and was supported by the Berta-Ottenstein-Program for Clinician Scientists from the Faculty of Medicine, University of Freiburg. GK reports personal fees from Desitin Arzneimittel, Eisai, GW Pharmaceuticals companies, UCB, Novartis, Takeda, and Zogenix. TM reports personal fees and grants from Arvelle Therapeutics, Eisai, GW Pharmaceuticals companies, UCB, and Zogenix. SM reports grants from Novartis, UCB, Shire, Deutsche Forschungsgemeinschaft and Epilepsiestiftung Dr. Wolf. HM reports personal fees from Desitin Arzneimittel, UCB, Novartis and Zogenix. KMS reports personal fees from Nutricia, Desitin Arzneimittel, Shire, Medice, Novartis and UCB. FvP reports personal fees and grants from Bial, Desitin Arzneimittel, Eisai, GW Pharmaceutical companies, Arvelle Therapeutics, and UCB Pharma. FR reports personal fees from Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceuticals companies, Novartis, Medtronic, and UCB, and grants from the Detlev-Wrobel-Fonds for Epilepsy Research, the Deutsche Forschungsgemeinschaft, the LOEWE Programme of the State of Hesse, and the European Union. MS reports personal fees from Novartis and GW Pharmaceuticals companies. SK reports speaker´s honoraria from Arvelle Therapeutics, Bial, Epilog, Desitin Arzenimittel, Eisai, Precisis AG and UCB. SS-B reports personal fees from Eisai, Desitin Pharma, GW Pharmaceuticals companies, LivaNova, UCB, and Zogenix. RT reports personal fees from Eisai, Desitin, PTC Therapy., Roche, Sanofi Genzyme. AW-K reports personal fees from Desitin Arzneimittel, GW Pharmaceuticals companies, Nutricia GmbH, Vitaflo, and UCB. BW reports fees and compensation for travel expenses from Eisai, Takeda/Shire, Ipsen, and PharmAllergan. JPZ reports speakers’ honoraria and travel grants from Eisai and Desitin Arzneimittel. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Authors’ contributions

AS, JG, CH, GK, MK, FR, MS, SSB, AWK, and JPZ developed the idea for this study. AS and JPZ conceived the paper and performed the statistical analysis. JPZ created the charts and figures. AS and JPZ performed the literature review of studies examining prescription patterns. All authors wrote the paper, discussed the results, contributed to the final manuscript, and approved the final manuscript for publication.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by the State of Hessen with a LOEWE-Grant to the CePTER Consortium (https://www.uni-frankfurt.de/67689811).