Authors :
Presenting Author: Benjamin Cadle, BS – University of Louisville School of Medicine
Feride Un Candan, MD – Department of Neurology – University of Louisville School of Medicine; Zulfi Haneef, MD – Department of Neurology – Baylor College of Medicine; Christopher Barton, MD – Department of Neurology – University of Louisville School of Medicine; Dylan Brock, MD – Department of Neurology – University of Louisville School of Medicine; Irfan Ali, MD – Department of Pediatrics – Baylor College of Medicine; Cemal Karakas, MD – Department of Neurology – University of Louisville School of Medicine
Rationale:
Hypersensitivity reactions (HR) to anti-seizure medications (ASMs) pose a significant challenge in the management of epilepsy, impacting both patient safety and treatment efficacy. The lack of robust data on HR related to individual ASMs and subsequent ASMs, largely due to limited sample sizes in previous studies, hinders clinicians' ability to accurately gauge the risk and implement effective treatment strategies. Furthermore, data on reactions to multiple ASMs, which is an increasingly common scenario in clinical practice, is sparse, limiting our understanding of potential synergistic risk factors. By harnessing a large dataset, this study aims to bridge these gaps in knowledge and provide a nuanced understanding of HR related to ASMs.
Methods:
We utilized the Slicer-Dicer tool, an analytical function within the Epic electronic medical records system, to analyze a single institution's patient data from 2012 to 2020. This dataset consisted of 573,571 patients who had a combined total of 967,168 exposures to 31 distinct ASMs. We determined the incidence of HR associated with each ASMs. In addition, we sought to understand how the likelihood of HR varied by gender and the generation of the drug (i.e., pre-2000 or post-2000). One of our key areas of investigation was the number of patients who experienced HR to two different ASMs at any point. This allowed us to identify specific pairs of ASMs that may be associated with a heightened risk of HR, thereby providing crucial insights into potential risk factors in multi-drug therapies.
Results:
Phenobarbital was associated with the highest incidence (12.9%) of HR. In terms of drug pairings, carbamazepine and its associated drugs, oxcarbazepine and eslicarbazepine, stood out. These three ASMs were implicated in the largest number of instances (19 in total) where patients experienced HR to both drugs at some point during the study period. Other significant ASM pairings involved phenobarbital (six pairings) and lamotrigine (four pairings). Females were more likely to experience HR with 13 out of the 31 ASMs. Interestingly, lacosamide was the only ASM with a higher incidence of HR in males. We found no significant difference (p=0.39) in HR rates between ASMs introduced pre-2000 and post-2000. Finally, we identified a higher risk of HR than previously reported for several ASMs, including clobazam (0.6%), primidone (0.8%), lacosamide (0.6%), brivaracetam (0.5%), perampanel (0.8%), vigabatrin (1.4%), rufinamide (0.8%), and cannabidiol (0.5%).
Conclusions:
This study provides a broader and more nuanced understanding of HR related to ASMs, emphasizing the need for personalized patient-centric approaches in epilepsy treatment. Clinicians are encouraged to weigh these findings while initiating new ASM therapy, particularly considering the highlighted ASMs and their associated HR risks. Future research is warranted to further understand the implications of these findings and to develop strategies to mitigate HR risks in epilepsy management.
Funding: None.