Safety evaluation of Tofersen in amyotrophic lateral sclerosis based on the FAERS database

Background: This study utilizes data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) to conduct a post-marketing safety evaluation of Tofersen. Methods: A systematic search of the FAERS database was performed to identify adverse event (AE) reports from Q1 2023 to Q4 2025 was performed. Multi-dimensional disproportionality analyses were conducted using the ROR, PRR, BCPNN, and MGPS method. Results: A total of 409 Tofersen-related reports were identified, revealing significant signals across 22 System Organ Class (SOC) categories and 369 Preferred Terms (PTs). At the SOC level, the most prominent safety signals were observed in injury, poisoning and procedural complications, nervous system disorders, and musculoskeletal and connective tissue disorders. In contrast, ear and labyrinth disorders, as well as respiratory, thoracic and mediastinal disorders, were not listed in the current product labeling and may warrant further investigation. At the PT level, neurological procedural complication, CSF red blood cell count positive, CSF white blood cell count increased, and CSF cell count increased exhibited the strongest signals, primarily reflecting cerebrospinal fluid cytological and biochemical abnormalities, as well as procedural-related adverse events such as post-lumbar puncture syndrome, procedural pain, and procedural headache. Although central nervous system-related events (e.g., increased intracranial pressure, peroneal nerve palsy, papilloedema, and facial paralysis) and infectious or inflammatory events (e.g., radiculopathy, myelitis, aspiration pneumonia, and meningitis) were less frequently reported, their relatively high disproportionality signals warrant clinical attention and systematic monitoring. Notably, a newly identified signal of pulmonary embolism suggests a potential thromboembolic risk in specific patient populations. Conclusion: These findings provide real-world evidence to inform the balance between the therapeutic potential and safety profile of Tofersen. Future clinical strategies should focus on mitigating central nervous system-related and procedure-related adverse events. Further mechanistic studies are crucial.