Clarifying the role of perampanel in pediatrics with Dravet syndrome: addressing concerns and evidence
In the initial paragraph of the Letter to Editor by Khan et al. [2024] (1), the relationship between perampanel (PER) response and varying seizure semiology in children with Dravet syndrome (DS) emerges as a multifaceted research domain. PER, acting as a selective non-competitive AMPA receptor antagonist, has demonstrated efficacy in reducing seizure frequency across different seizure types, encompassing generalized tonic-clonic and focal seizures. Our study (2) particularly accentuated the seizure profile of each patient, as delineated in Tab. 1, offering a comprehensive overview of individual characteristics, including age, weight, age of seizure onset, and other pertinent factors known to influence treatment response. Tab. 4 provides a detailed breakdown of each child’s response, aligning with existing studies that suggest PER’s effectiveness in specific seizure semiologies. Thus, our study does not generalize PER as universally effective across all seizure types but in contrast, our study provides detailed information based on each patient.
Regarding the second paragraph, we appreciate your acknowledgment to the strength of our methodology, we mentioned in detail the included patients and the specific criteria that make them eligible to be selected. Such criteria, as mentioned in the main article, are based on standardized guidelines (i.e., International League Against Epilepsy 2022 definition) and previous literature. On the issue of children’s co-morbidities, it is known that children with DS often face numerous comorbidities, including developmental delays, behavioral issues, and motor impairments such as ataxia and hypotonia. Therefore, removing patients based on their co-morbidities to avoid potential confounders is unachievable. Regarding the patient who achieved complete seizure freedom and was on the highest PER, there was a lack of statistical association. We emphasized that despite the lack of statistical associations we had evidence of a single patient achieving seizure freedom after adding PER to their course of treatment, correlating a potential relationship that was tested in the study. Moreover, the lack of a large sample contributes to this limitation which we emphasized in the limitation section despite our study being one the largest studies with DS patients.
Furthermore, the concise discussion on side effects and the absence of life expectancy considerations stem from the limited patient cohort and treatment duration within our study, particularly given the off-label use of the medication as disclosed in the materials and methods section. In studies measuring efficacy and tolerability it is not a primary objective to investigate and provide steps on how to deal with such patients which require other multidisciplinary papers given the complex management these patients require.
We agree on the need to further elaborate on the pathophysiology of PER, molecular insights into the mechanisms of this medication specifically in children with DS, and measures that could increase PER efficacy and decrease its adverse effects as you eloquently described in the last paragraph.
Acknowledgments
Funding: None.
Footnote
Provenance and Peer Review: This article was commissioned by the editorial office, Translational Pediatrics. The article did not undergo external peer review.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2024-508/coif). The authors have no conflicts of interest to declare.
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References
- Khan SM, Khan KH, Imam F. Evaluating concerns for perampanel in the treatment of pediatric Dravet syndrome. Transl Pediatr 2024; [Crossref]
- Muthaffar OY, Bamaga AK, Alyazidi AS, et al. Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome. Transl Pediatr 2024;13:584-95. [Crossref] [PubMed]
