Kaposi's Sarcoma in patients exposed to calcineurin inhibitors or systemic corticosteroids: A two-decade real-world safety assessment.

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Background: Kaposi’s Sarcoma (KS) is a rare angioprolefrative tumor, occurring in approximately 2 per 1 million in the United States. Although the iatrogenic variant is primarily linked to immunosuppressive therapy, evidence on drug specific-induced KS risk remains limited. This study assesses the association between KS and exposure to immunosuppressive agents. Methods: We conducted a retrospective pharmacovigilance analysis using U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS), retrieving reports involving calcineurin inhibitors and corticosteroids from 2004 Q1 to 2024 Q1, Disproportionality analyses were performed by Reporting Odds Ratios (RORs), Proportional Reporting Ratios (PRR), and Bayesian shrinkage metrics, including the Information Component and its lower 95% credibility bound (IC025). A signal was considered present when IC025 exceeded zero. Descriptive analyses were also performed. All data cleaning and statistical analyses were performed in R (version 2025.09.2+418). Results: A total of 668 reports of KS in patients exposed to cyclosporine, tacrolimus, prednisone, or methylprednisolone were identified. Prednisone demonstrated the strongest disproportionality signal (n=175, ROR 40.14 [34.42-46.80], PRR 39.91, IC025 5.01), followed by tacrolimus (n=241, ROR 31.12 [27.2-35.5], PRR 30.9, IC025 4.65), methylprednisolone (n= 97, ROR 27.62 [22.5-33.8], PRR 27.5, IC025 4.44) and cyclosporine(n=155, ROR 23.58 [20.0-27.7], PRR 23.5, IC025 4.25). KS occurred predominantly in males (68.1%), with a median age of 54 years, and was most frequently associated with renal transplant indications (10.8%). Mortality was highest with cyclosporine-associated cases (21.9%). Time-to-onset analysis revealed the shortest latency with methylprednisolone (median 51.5 days), while tacrolimus showed the longest latency (median 344.5 days). Conclusions: Although FAERS cannot distinguish iatrogenic KS from other variants, all four agents showed strong signals for KS. Cyclosporine associated cases had the highest mortality. and the marked differences in latency patterns between corticosteroids and calcineurin inhibitors suggest distinct drug class risk profiles.