Relationship between Anaplastic Lymphoma Kinase (ALK) Inhibitors and Epileptic Seizure Disorder: A Post-Marketing Surveillance Study.

Introduction: ALK has been to be involved in the uptake and regulation of D2R, a G protein-coupled receptor expressed in various brain regions. Therefore, it is crucial to understand the relationship between ALK inhibitors and seizures is an important issue. This study investigated the relationship between ALK inhibitors and seizures. Methods: This study investigated the relationship between ALK inhibitors and seizures through a disproportionality analysis using the FAERS. The target drugs were the ALK inhibitors crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. The seizures covered were defined HLGT: ''Seizures (incl subtype)'' including HLT: ''Seizures and seizure disorders NEC.'' This study used the IC, a signal score, as a Bayesian statistical method for disproportionality analysis. Results: The signal scores of ''Seizures and seizure disorders NEC'' for each ALK inhibitor were crizotinib (IC: -0.00052, 95%CrI: -0.38–0.27), ceritinib (IC: 1.18, 95%CrI: 0.68–1.54), alectinib (IC: 0.68, 95%CrI: 0.19–1.02), brigatinib (IC: 1.04, 95%CrI: 0.32–1.54), and lorlatinib (IC: 0.82, 95%CrI: 0.11–1.32). On the other hand, ''Generalized tonic-clonic seizures'', ''partial simple seizures NEC, '' ''Absence seizures,'' and ''partial complex seizures'' had no or few reported cases, and no signal was detected. Conclusion: To our knowledge, this is the first report to evaluate the relationship between ALK inhibitors and seizures using post-marketing surveillance data. These results suggest that ceritinib, alectinib, brigatinib, and lorlatinib, which are highly brain-migrating drugs, are associated with seizures.