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(Abst. 3.331), 2019

Rescue Medications in Seizure Clusters: A Systematic Review of Treatment Patterns and Treatment Impact
Authors: Saifuddin Kharawala, Bridge Medical Consulting Ltd, London, UK; Jerzy P. Szaflarski, University of Alabama at Birmingham; Gavneet Kaur, Bridge Medical Consulting Ltd, London, UK; Eun Jung Choi, UCB Pharma, Smyrna, GA, USA; Jessica Claire Wilson, UCB Pharma, Brussels, Belgium; Lawrence J. Hirsch, Yale School of Medicine
Content: Rationale: Benzodiazepines, including diazepam, lorazepam, and midazolam are used as rescue medications (RMs) in patients with epilepsy. A seizure cluster (SC) is a seizure emergency that presents with multiple seizures that occur within a short period of time. In SCs, RMs are used to abort cluster episodes with the goal of reducing the risk of subsequent seizures and complications of escalating seizures, e.g. status epilepticus (SE). The patterns of RM prescription and utilization in SC, as well as the overall impact of RM treatment on clinical, humanistic, and economic burden in SC have not been assessed in a systematic manner. Methods: A systematic literature search was conducted to identify all articles reporting the use of RMs in patients with SC. The search was conducted in PubMed and Embase databases, using the interface. This was supplemented with keyword-based searches in PubMed, Google, and Google Scholar. Finally, bibliographic searches were conducted of relevant primary studies and reviews. A 2-step screening process (title/abstract followed by full-text screening) was followed to identify and include relevant articles reporting data on treatment patterns of RMs and/or impact of RM treatment on clinical, humanistic, and economic burden in SC. English-language articles published after the year 2000 were included. Results: In SC outpatients, RMs were prescribed for 28-90% and utilized by 16-45% of patients (Fig. 1). RM utilization rates were, however, significantly higher in SC compared to non-SC patients (26.4% vs 10.8%, respectively). Primary reasons for RM under-utilization included lack of seizure emergency plans, poor physician-patient communication, and concerns with route of administration. Seizure emergency plans were in place for 31% of adult and 78% of pediatric SC patients. SC patients appeared to preferentially seek out emergency care as their first response for managing SC; while most clinicians (79%) advised their patients to use RMs during a SC episode, only 20% of patients reported that they would use an RM during an episode. The most commonly used RM was oral lorazepam in adults, and rectal diazepam in children. During a cluster episode, RM was administered by caregivers after a median of 4 seizures, and at a median of 93 minutes after onset. Limited available comparative effectiveness data showed that SC patients preferred buccal midazolam over rectal diazepam in view of its efficacy and ease of use. In the real-world, 77-95% of SC patients experienced seizure cessation with RMs. Consistent use of RMs was associated with a reduced risk of progression to SE and lower healthcare resource utilization. RM prescription was associated with a significant decrease in parental stress. Conclusions: RMs are under-prescribed and under-utilized in SC patients, especially in adults. RM utilization rates are much lower than prescription rates. In adult patients, lack of seizure emergency plans and issues with route of administration are key reasons for RM under-utilization. The role of RMs in SC management is characterized differently by clinicians and patients. RMs effectively terminate SCs and are associated with improved clinical, humanistic and economic outcomes; therefore, addressing the issue of RM under-utilization in SC patients is critical. Funding: UCB Pharma-sponsored
Figure 1