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Temporal, Phenotypic, and Treatment-Context Heterogeneity in Retinal Vasculitis Reporting with Pegcetacoplan: A United States Pharmacovigilance Study

Year: 2026
Type: article
Study design: Observational Study
Abstract: Background/Objectives: Pegcetacoplan slows geographic atrophy (GA) progression, but postmarketing retinal vasculitis remains an important safety concern. We evaluated whether retinal vasculitis reporting changed over time, whether the reported phenotype changed with respect to occlusive coding, and whether vasculitis was associated with identifiable treatment contexts. Methods: We analyzed the United States (US) Food and Drug Administration Adverse Event Reporting System (FAERS) data from 17 February 2023 through 31 December 2025. Strict retinal vasculitis reports required pegcetacoplan to be coded as the primary-suspect drug. Faricimab was used as a descriptive contemporaneous intravitreal comparator because US exposure estimates could be constructed over the same period; it was not treated as a safety-neutral control. Separately, within all US primary-suspect Syfovre reports, we examined whether another anti-vascular endothelial growth factor (anti-VEGF) agent was co-reported. These anti-VEGF agents were evaluated as treatment-context variables rather than as temporal comparators. Results: We identified 79 US primary-suspect Syfovre retinal vasculitis reports, of which 58 had quarter-assignable clinical event dates. Overall, 42/79 (53.2%) contained an occlusive-specific vasculitis preferred term and 37/79 (46.8%) did not. Pegcetacoplan reporting declined from 4.09 to 0.38 reports per 10,000 estimated vials between the pre-change and post-change periods (reporting-rate ratio 0.09, 95% confidence interval [CI] 0.05–0.16; p < 0.001). Faricimab reporting also declined; the ratio of reporting-rate ratios was 0.79 (95% CI 0.22–2.78; p = 0.711), with wide uncertainty. Among temporally assignable pegcetacoplan reports, occlusive-specific coding decreased from 16/21 (76.2%) before the change to 8/30 (26.7%) afterward (p < 0.001). Another anti-VEGF agent was listed in 19/79 vasculitis reports versus 50/571 nonvasculitis reports (reporting odds ratio 3.30, 95% CI 1.83–5.96; p < 0.001); however, adjustment for medication count and report completeness attenuated the estimate to 1.89 (95% CI 0.99–3.61; p = 0.052). Conclusions: Pegcetacoplan retinal vasculitis reporting declined over time, but the descriptive faricimab comparison was too imprecise to determine whether the proportional temporal change differed between products. The reported phenotype shifted away from occlusive-specific coding, while the anti-VEGF co-reporting association was sensitive to adjustment for documentation intensity. These findings characterize heterogeneity in spontaneous safety reporting and do not establish patient-level risk, changes in clinical event severity, or causal treatment effects.
DOI: 10.3390/jpm16100533
Language: English
Subfield: Toxicology
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W7222624485
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