A Distinct Delayed-Onset Intraocular Inflammation Phenotype of Faricimab versus Aflibercept and Ranibizumab: Triangulated Pharmacovigilance Evidence from Databases of US, Europe and Japan

@misc{jiang2026distinct,
  title = {{A Distinct Delayed-Onset Intraocular Inflammation Phenotype of Faricimab versus Aflibercept and Ranibizumab: Triangulated Pharmacovigilance Evidence from Databases of US, Europe and Japan}},
  author = {J. Jiang and Y. Gu and D. Hu and X. Li and S. Qin and Q. Ling and Q. Zhang and L. Dong and Z. Lin},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.10.26365218},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.10.26365218v1},
  note = {CC BY-NC},
}

TY  - UNPB
TI  - A Distinct Delayed-Onset Intraocular Inflammation Phenotype of Faricimab versus Aflibercept and Ranibizumab: Triangulated Pharmacovigilance Evidence from Databases of US, Europe and Japan
AU  - J. Jiang
AU  - Y. Gu
AU  - D. Hu
AU  - X. Li
AU  - S. Qin
AU  - Q. Ling
AU  - Q. Zhang
AU  - L. Dong
AU  - Z. Lin
PY  - 2026
DA  - 2026/10/10
PB  - medRxiv
DO  - 10.64898/2026.10.10.26365218
UR  - https://www.medrxiv.org/content/10.64898/2026.10.10.26365218v1
AB  - PurposePost-marketing reports have associated faricimab, the first intravitreal bispecific antibody, with intraocular inflammation (IOI). Its inflammatory phenotype, temporal pattern, and systemic safety relative to established anti-VEGF agents remain unclear. We compared faricimab with aflibercept and ranibizumab across three independent pharmacovigilance databases.  DesignTriangulated Pharmacovigilance study.  MethodsWe analyzed FAERS reports (Q1 2022-Q2 2026) with external validation in JADER (Japan) and EudraVigilance (Europe). After de-duplication and restriction to primary-suspect reports, we computed reporting odds ratios (RORs) with false discovery rate control, derived confounder-adjusted RORs by logistic regression, modeled time-to-onset (TTO) with Weibull distributions, and graded signals with a pre-specified bidirectional cross-database evidence framework.  ResultsThe FAERS cohort comprised 6,833 faricimab, 6,714 aflibercept, and 2,533 ranibizumab reports. Faricimab showed higher reporting of anterior-chamber and vitreal inflammation: adjusted RORs (comparator versus faricimab; values <1 indicate faricimab excess) were 0.27 (95% CI 0.18-0.40) for iridocyclitis and 0.45 (0.35-0.58) for uveitis versus aflibercept, and 0.13 (0.06-0.24) and 0.12 (0.06-0.20) versus ranibizumab. All four core IOI preferred terms were Confirmed in JADER against both comparators. Faricimab IOI arose late (median TTO 100 vs 7 days; P = 2.6E-14) with a markedly flatter Weibull distribution (shape 0.81 vs {approx}0.42). Aflibercept predominated for endophthalmitis-spectrum and intraocular pressure events; ranibizumab for vitreous hemorrhage (confirmed in JADER). Faricimab showed lower reporting across cardiac, nervous system, vascular, and renal organ classes, confirmed in EudraVigilance. An unadjusted death signal did not survive adjustment and was absent in outcome-based JADER analyses.  ConclusionsFaricimab exhibits a reproducible, delayed-onset, anterior-predominant IOI phenotype alongside a comparatively favorable systemic safety profile. Clinicians should recognize that faricimab-associated IOI may arise weeks to months after injection.  HighlightsFaricimab showed higher reporting of anterior and intermediate intraocular inflammation than aflibercept and ranibizumab across three independent databases.  Faricimab-associated inflammation arose late, with a median onset of 100 days versus 7 days for the comparators.  Aflibercept predominated for endophthalmitis-spectrum events and ranibizumab for vitreous haemorrhage.  No drug showed excess death reporting after adjustment and outcome-field verification.
ER  -