Global burden of TNF-α inhibitors associated demyelinating diseases: A global disproportionality analysis

Despite case reports linking tumor necrosis factor-alpha (TNF-α) inhibitors to demyelinating diseases, large-scale epidemiological evidence is limited. We aimed to investigate this signal detection using a global pharmacovigilance database. This study identified reports of TNF-α inhibitor-associated demyelinating disease utilizing a global pharmacovigilance database spanning from 1968 to 2024. Five TNF-α inhibitors (infliximab, adalimumab, etanercept, certolizumab pegol, and golimumab) were included in this study. The signal detection between TNF-α inhibitors and demyelinating disease was evaluated using disproportionality analysis with 2 metrics: the information component (IC) with a threshold of IC025, and the reporting odds ratio (ROR) with a 95% confidence interval (CI). Statistical significance was defined as an IC025 > 0.00 and the lower bound of the CI > 1.00. A total of 4124 reports of demyelinating diseases associated with TNF-α inhibitor use were identified. Multiple sclerosis was the most frequently reported condition (n = 2079, 50.41%). Overall, TNF-α inhibitors indicated a significant association with demyelinating diseases (ROR, 1.81 [95% CI: 1.75-1.87]; IC, 0.84 [IC025, 0.78]). Significant signal detections were observed for all 5 individual TNF-α inhibitors. Both multiple sclerosis (ROR, 1.52 [95% CI: 1.46-1.59]; IC, 0.60 [IC025, 0.43]) and Guillain-Barré syndrome (ROR, 1.53 [95% CI: 1.40-1.68]; IC, 0.60 [IC025, 0.45]) showed significant signal detection with TNF-α inhibitors. This large-scale pharmacovigilance study confirmed significant signal detection between TNF-α inhibitors and several demyelinating diseases, particularly multiple sclerosis and Guillain-Barré syndrome, with signals observed across most agents. Clinicians should remain vigilant for neurological symptoms in patients receiving these therapies. Although this disproportionality analysis did not permit causal interpretation, it is important to recognize that the therapeutic benefits of TNF-α inhibitors in managing inflammatory and autoimmune diseases may still outweigh these potential risks.