Comparative Efficacy, Durability and Safety of Faricimab in the Treatment of Diabetic Macular Edema: A Systematic Literature Review and Network Meta-Analysis

Abstract

Introduction: A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16 weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice.

Methods: An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12 months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible.

Results: Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55-125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4-4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92-1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations.

Conclusion: Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab.

Keywords: Comparative efficacy; Diabetic macular oedema; Durability; Faricimab; Network meta-analysis; Safety; Systematic literature review.

Fig. 1

PRISMA diagram of the studies included in the systematic literature review

Fig. 2

Network for mean change in best-corrected visual acuity (BCVA) score from baseline to 12 months. AFL aflibercept, BEV bevacizumab, DEX dexamethasone, FAR faricimab, IVT intravitreal, PBO placebo, PRN treatment as needed (pro re nata), Q4/8/16W every 4/8/16 weeks, RAN ranibizumab, T&E treat and extend. Colour-coded nodes illustrate the number of steps (pairwise comparisons) between faricimab and a given comparator to highlight how they are connected and what informs the estimation of the treatment effect. Blue = randomized controlled trial, red = 1 step, green = 2 steps, Yellow = 3 steps

Fig. 3

Forest plot of results obtained through the network meta-analysis for A mean change in BCVA at 12 months from baseline, B mean change in central subfield thickness (CST) at 12 months from baseline, C injection frequency at 12 months, D ocular adverse events at 12 months and E all cause discontinuation. AFL aflibercept, BEV bevacizumab, DEX dexamethasone, FAR faricimab, IVT intra-vitreal treatment, LP loading phase, OLE open label extension, PBO placebo, PRN pro re nata, Q6/8/12/16W every 6/8/12/16 weeks, RAN ranibizumab, CrI credible interval

Fig. 3

Forest plot of results obtained through the network meta-analysis for A mean change in BCVA at 12 months from baseline, B mean change in central subfield thickness (CST) at 12 months from baseline, C injection frequency at 12 months, D ocular adverse events at 12 months and E all cause discontinuation. AFL aflibercept, BEV bevacizumab, DEX dexamethasone, FAR faricimab, IVT intra-vitreal treatment, LP loading phase, OLE open label extension, PBO placebo, PRN pro re nata, Q6/8/12/16W every 6/8/12/16 weeks, RAN ranibizumab, CrI credible interval