To evaluate the association between biologic therapies for rheumatologic disorders and inflammatory bowel diseases (IBD) and the occurrence of demyelinating adverse events using the FDA Adverse Event Reporting System (FAERS).

Comparative analyses of demyelination-related safety signals across different classes of biologic therapies used for rheumatologic disorders and IBD remain limited. Newer agents have less post-marketing data regarding demyelination risk. Pharmacovigilance-based detection of safety signals can help guide clinical decision-making and regulatory oversight.

We performed a disproportionality analysis of FAERS data from the fourth quarter of 2003 through the second quarter of 2025 to evaluate demyelinating events associated with anti-rheumatic and anti-IBD biologic therapies. Mechanistic classes included: anti–tumor necrosis factor (TNF)-α agents, anti-integrin antibodies (excluding natalizumab), anti-interleukin agents (including IL-12/23, IL-23, IL-17, IL-6, and IL-1 inhibitors), B-cell targeted therapies (excluding rituximab), and T-cell co-stimulation modulators. The preferred term “demyelination” was used to identify relevant adverse events. A safety signal was defined according to Evans criteria as ≥3 reports, a proportional reporting ratio (PRR) ≥2, and a chi-squared value ≥4.

Safety signals for demyelination were identified with TNF-α inhibitors (infliximab, adalimumab, certolizumab pegol, golimumab, and etanercept) with a PRR of 7.34 (95% CI: 6.75–7.98), and abatacept, a selective T-cell co-stimulation modulator (PRR: 2.12; 95% CI: 1.41–3.20). No safety signals were observed for IL-12/23 inhibitors (ustekinumab), IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab), IL-23 inhibitors (mirikizumab, guselkumab, tildrakizumab, risankizumab), and anti-α4β7 integrin (vedolizumab). Reporting counts were insufficient for IL-6 inhibitors (tocilizumab and sarilumab), IL-1 inhibitors (anakinra, canakinumab, and rilonacept), and B-lymphocyte stimulator (belimumab) to allow disproportionality analysis.

Our findings confirm strong pharmacovigilance signals for demyelination with TNF-α inhibitors and suggest a possible signal with abatacept, whereas newer interleukin and integrin inhibitors did not demonstrate similar associations. These results support continued vigilance and post-marketing surveillance to better define demyelination risk across biologic classes.