Male sexual dysfunction associated with TNF-α inhibitors: an indication-stratified global pharmacovigilance analysis

Tumor necrosis factor-α (TNF-α) inhibitors are widely used for chronic inflammatory diseases, but their effects on male sexual health remain uncertain. We investigated whether male sexual dysfunction (MSD) reporting varied across TNF-α inhibitors and clinical indications.

We screened MSD reports associated with TNF-α inhibitors in WHO VigiAccess and performed a disproportionality analysis of individual case safety reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from 2004 to 2025. Four disproportionality algorithms were used to evaluate overall, indication-specific, and preferred term (PT)-specific reporting patterns. Time-to-onset was assessed using Weibull modeling.

No overall positive MSD signal was detected for any TNF-α inhibitor. In ankylosing spondylitis (AS), indication-level reporting odds ratio (ROR) signals were observed for adalimumab (ROR 1.80, 95% CI 1.11-2.92) and etanercept (ROR 2.21, 95% CI 1.37-3.55), but their direct comparison was not significant (ROR ratio 0.81, 95% CI 0.41-1.61). No positive PT-specific ROR signal was detected for either drug in AS. Among reports with usable onset dates, Weibull analysis suggested earlier reporting patterns.

MSD reporting with TNF-α inhibitors may vary by clinical indication rather than represent a uniform class-wide pattern. The AS findings warrant cautious interpretation because both agents showed indication-level signals without a significant between-drug difference or positive PT-specific signals. These findings are hypothesis-generating and require prospective confirmation.