Disproportionality Analysis and Timing of Drug-Associated Guillain-Barré Syndrome Onset Based on the Japanese Adverse...

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 suggested as potential triggers of GBS. This study investigated drug-associated GBS using a spontaneous adverse event reporting database through disproportionality analysis for signal detection and time-to-onset analysis. Methods: The Japanese Adverse Drug Event Report (JADER) database was analyzed to assess more than 4000 drugs for potential 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, time-to-onset patterns were further evaluated using Weibull distribution analysis. Results: Disproportionality signals suggesting potential associations with GBS were identified for 45 drugs, including vaccines, immune checkpoint inhibitors, tumor necrosis factor-α inhibitors, other anticancer drugs, antifungal agents, and interferons. Reports following vaccination were most frequently observed within 1-3 weeks after administration of coronavirus disease 2019 (COVID-19), influenza, and pneumococcal vaccines, and within 1-3 months after human papillomavirus 2-valent vaccination, with a gradual decrease thereafter. Reports following immune checkpoint inhibitor use were most frequently observed 1-3 months after nivolumab, ipilimumab, and pembrolizumab administration, whereas atezolizumab showed a peak in reporting within 1-3 weeks. In contrast to vaccine-related reports, no clear temporal trend in reporting was observed. Conclusions: Drugs that modulate immune function, including vaccines and immune checkpoint inhibitors, may be associated with reported GBS events. Vaccine-related reports showed an early concentration in time to onset, whereas immune checkpoint inhibitor-related reports did not demonstrate a clear temporal pattern. These findings should be interpreted as hypothesis-generating and warrant further investigation.