FAERS analysis flags 13 systemic medications with high uveitis reporting signals
A FAERS database analysis identified 13 FDA-approved systemic medications with disproportionately high uveitis reporting signals among 7,301 events from 2003 to 2024. The strongest signals were for cidofovir and rifabutin, and the findings were described as hypothesis-generating rather than causal.
A new FAERS database analysis identified 13 FDA-approved systemic medications with disproportionately high uveitis reporting signals among 7,301 adverse events logged from 2003 to 2024. The strongest safety signals were observed for cidofovir and rifabutin. While the findings are hypothesis-generating and cannot establish causality, they reinforce the importance of monitoring at-risk patients for ocular inflammation when prescribing immunologic, anti-infective or oncologic therapies.
Among the etiologies of uveitis, medications such as bisphosphonates, immune checkpoint inhibitors and moxifloxacin have been identified as potential contributors to the disease. However, population-based research of drug-related uveitis remains limited. Researchers conducted disproportionality analyses by comparing drug-specific uveitis reports with the background reporting rate across all other drugs in the database, and reporting odds ratios with 95% confidence intervals were calculated.
The study included a total of 7,301 uveitis events between 2003 and 2024. The mean age of patients in these reports was 49.9 ± 20 years. Overall, 31.9% of patients were male, 49.3% were female, and 18.8% did not report sex. Most uveitis cases, 56.5%, were reported after 2022. The highest proportion of cases was reported in North America at 49.6%, followed by Europe at 28.4% and Asia at 11.5%.
According to the results, 13 pharmacological agents were identified as being disproportionately associated with high reporting rates of uveitis:
- cidofovir (ROR = 103.8)
- rifabutin (ROR = 77.4)
- cobimetinib (ROR = 30.5)
- foscarnet (ROR = 29.0)
- infliximab (ROR = 18.1)
- dabrafenib (ROR = 16.4)
- vemurafenib (ROR = 16.2)
- trametinib (ROR = 15.5)
- brodalumab (ROR = 14.9)
- binimetinib (ROR = 11.3)
- encorafenib (ROR = 11.2)
- ipilimumab (ROR = 11.0)
- moxifloxacin (ROR = 10.3)
Interpretation of these associations must consider underlying disease indications, which may independently predispose patients to ocular inflammation. Cidofovir and foscarnet are antivirals predominantly used in immunocompromised individuals, particularly those with cytomegalovirus retinitis, where ocular inflammation is an inherent feature of the disease process. Rifabutin and moxifloxacin are commonly prescribed for infectious conditions, such as Mycobacterium avium complex and bacterial respiratory infections, which can independently trigger ocular inflammation through immunity-mediated or microbial mechanisms.
In contrast, biologic agents, MEK inhibitors and BRAF inhibitors are primarily used in autoimmune and oncologic settings, including rheumatoid arthritis, psoriasis and melanoma, where immune dysregulation or paraneoplastic inflammation may overlap with drug-related effects. Differentiating between disease-associated and drug-induced uveitis therefore remains challenging and highlights the need to integrate pharmacovigilance findings with clinical context in future studies.
Patients at greatest risk include those with pre-existing autoimmune or inflammatory disorders, prior ocular inflammation, or infectious etiologies such as cytomegalovirus retinitis. Individuals receiving multiple immunomodulatory or cytotoxic agents, or those with cancer-related immune dysregulation, may also exhibit amplified susceptibility to drug-induced uveitis. Proposed mechanisms include immune complex deposition, immune checkpoint dysregulation, cytokine imbalance and direct ocular toxicity.
A review of published literature on drug-induced uveitis found that 317 articles with 690 unique patient cases met inclusion criteria for case-level data analysis. The mean age at drug-induced uveitis onset was 54.4 years; 63.4% had bilateral disease, and 74.8% had anterior uveitis. Mean exposure time from first dose to uveitis onset was 197.2 days, and mean resolution time was 61.0 days. Antineoplastics, vaccines, antibiotics, intraocular pressure-lowering drops, bisphosphonates, vascular endothelial growth factor inhibitors, antivirals, and disease-modifying antirheumatic drugs were the most frequently implicated classes.
Drug-induced uveitis, although rare, represents a broad array of presentations, mechanisms and clinical course. Limitations of the FAERS analysis included voluntary reporting, which may result in under-reporting, selective reporting and incomplete data. Disproportionality analysis identifies potential associations but cannot account for exposure timing or establish causality, as it relies on relative reporting frequencies rather than absolute risk.