Disproportionality analysis of pyoderma gangrenosum reporting to the FDA Adverse Event Reporting System in association with antirheumatic biologics.

BACKGROUND

Several cases of pyoderma gangrenosum, a rare neutrophilic dermatosis, have been reported in patients initiating biological therapies for rheumatic health conditions. Despite this, systematic analysis across available therapies is lacking. This study investigated pyoderma gangrenosum reporting in association with antirheumatic biologics to the US Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS

Reports from FAERS (2016-second quarter of 2025) were complied, deduplicated, and standardized. Pyoderma gangrenosum cases were classified according to the Medical Dictionary for Regulatory Activities. Proportional reporting ratios (PRRs) and 95% confidence intervals (CIs) were calculated to estimate disproportionality for 20 individual antirheumatic biologics from nine pharmacologic classes.

RESULTS

During the study period, 13,284,367 adverse events were reported to FAERS, including 1316 pyoderma gangrenosum cases; 868 (65.96%) cases identified an antirheumatic biologic as the primary suspect product. Positive disproportionality signals were detected for 11 study biologics belonging to six pharmacologic classes. All four interleukin (IL)-17 inhibitors exhibited disproportionate pyoderma gangrenosum reporting, with brodalumab (PRR 23.02; 95% CI 8.64-61.36) and bimekizumab (PRR 9.10; 95% CI 4.08-20.29) demonstrating the strongest signals. Positive disproportionality signals were also observed among biologics targeting tumor necrosis factor alpha, IL-6, IL-12/23, IL-23, and CD20. Similar results were obtained in sensitivity analyses.

CONCLUSION

Despite its limitations, this hypothesis-generating analysis identified significantly disproportionate pyoderma gangrenosum reporting with several antirheumatic biologics. Clinicians should remain vigilant for these paradoxical reactions in patients undergoing biologic treatment for rheumatic conditions. Key points • Pyoderma gangrenosum has been reported in patients undergoing treatment with biologics for rheumatic indications. • This study analyzed spontaneous postmarketing pyoderma gangrenosum reporting in association with 20 antirheumatic biologics. • Pyoderma gangrenosum disproportionality signals were identified for 11 biologics targeting interleukin (IL)-6, IL-17, IL-12/23, IL-23, CD20, and tumor necrosis factor alpha.