Disproportionality Analysis and Timing of Drug-Induced Guillain–Barré Syndrome Onset Based on the Japanese Adverse Drug Adverse Event Report Database

Background: Guillain–Barré syndrome (GBS) is an autoimmune peripheral neuropathy that can lead to paralysis and respiratory failure. In addition to infections, several drugs have been identified as potential triggers of GBS. This study investigated drugs potentially associated with GBS and evaluated its onset timing using a spontaneous adverse event reporting database. Methods: The Japan Adverse Drug Event Report (JADER) database was analyzed to assess more than 4000 drugs for possible associations with GBS. Signal detection was performed using reporting odds ratios, Fisher’s exact test, and total report counts. For vaccines and immune checkpoint inhibitors, onset patterns were assessed using Weibull distribution analysis. Results: Signals suggestive of possible associations with GBS were identified for 45 drugs, including vaccines, immune checkpoint inhibitors, tumor necrosis factor-α inhibitors, non-immune checkpoint inhibitor anticancer drugs, antifungal drugs, and interferons. Vaccine-associated GBS frequently occurred within 1–3 weeks after coronavirus disease 2019, influenza, and pneumococcal vaccination and within 1–3 months after bivalent human papillomavirus vaccination, with the risk decreasing thereafter. Conversely, GBS associated with immune checkpoint inhibitors developed 1–3 months after nivolumab, ipilimumab, and pembrolizumab administration, whereas atezolizumab was linked to a peak onset within 1–3 weeks. Unlike vaccine-associated cases, no clear decline in risk over time was observed. Conclusions: Drugs that modulate immune function, including vaccines and immune checkpoint inhibitors, might be associated with GBS development. Vaccine-associated cases exhibit an early-onset pattern, whereas immune checkpoint inhibitor-associated GBS might occur irrespective of treatment duration. These findings support pharmacovigilance and adverse event monitoring.