UNVEILING THE ANTI-VEGF LANDSCAPE: AN INTEGRATIVE STUDY OF COMPARATIVE EFFECTIVENESS, COST-UTILITY, AND PHARMACOVIGILANCE

Abstract

Background: Intravitreal anti-angiogenic medications have recently grabbed the attention of researchers to control the pathology of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). This thesis aims to assess the differences in efficacy and safety between faricimab and aflibercept in patients with nAMD and DME through a comparative effectiveness analysis, specifically utilizing a meta-analysis approach. Additionally, it seeks to compare the cost-effectiveness of faricimab and aflibercept in nAMD patients from the payer's perspective in the United States. Furthermore, a pharmacovigilance study conducted to assess the real-world safety profile of faricimab in comparison to other anti-VEGF agents. Methods: A systematic review and meta-analysis were conducted by searching four academic databases, focusing on two efficacy outcomes, changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST), as well as three safety outcomes: conjunctival hemorrhage, serious adverse events (SAEs), and all-cause mortality. Standardized mean differences (SMDs) and relative risks were used to summarize the results, providing a comprehensive evaluation of faricimab and aflibercept in managing nAMD and DME. A Markov model was developed to compare faricimab (flexible dosing) and aflibercept over a five-year period, incorporating transition probabilities derived from x pooled estimates of data from two clinical trials and direct medical costs. Sensitivity analyses assessed the impact of key model parameters on cost-effectiveness. Additionally, a pharmacovigilance study evaluated the ocular safety profiles of faricimab, aflibercept, and ranibizumab using adverse event reports from the US FDA Adverse Event Reporting System (FAERS) from Q4/2003 to Q2/2024. The analysis, performed with OpenVigil 2.1, identified potential safety signals using MedDRA classification for AEs. Results: Four RCTs included 3220 patients. Faricimab had a significant lower mean change in CST than aflibercept (SMD = -0.24, 95%CI, -0.39 to -0.10, p = 0.001). BCVA did not differ. Conjunctival hemorrhage, SAEs, and all-cause mortality were similar across treatment arms. Base-case analysis demonstrated that faricimab is a cost-effective option, with a lower total cost ($51,913) and higher effectiveness (3.39 quality-adjusted life years (QALYs)) than aflibercept, which had higher costs ($61,210) and lower QALYs (3.29). Faricimab’s incremental cost-effectiveness ratio (ICER) dominated aflibercept ( $91,787.78 per QALY), reflecting better cost-effectiveness, mainly due to reduced injection frequency and related costs. The study also reports the AEs significantly linked to faricimab, aflibercept, and ranibizumab for the treatment of nAMD and DME. The findings include several novel AEs linked to faricimab, including Idiopathic orbital inflammation, hypopyon, and ocular vasculitis. xi Conclusion: Faricimab and aflibercept offer similar therapeutic benefits in treating retinal vascular diseases. However, further trials are necessary to confirm the significant reduction in central CST with faricimab in the treatment of in nAMD and DME. Faricimab offers superior economic value in treating nAMD in the USA, delivering comparable clinical benefits at lower costs than aflibercept. Its cost-effectiveness and reduced treatment burden support its potential as a preferred option for nAMD management from a payer’s perspective, suggesting benefits for healthcare systems by reducing costs and injection frequency. Faricimab-associated AEs are primarily linked to active inflammatory ocular disorders, while ranibizumab and aflibercept are more often associated with structural eye changes, lens disorders, ocular infections, or surgical effects. However, faricimab's safety profile remains incomplete due to limited post-marketing data.