Baseline Features in nAMD Not Predictive of Aflibercept 8 mg Intervals

Prof. Dr. med. Justus G. Garweg

Credit: Berner Augenklinik

Key baseline characteristics in eyes with neovascular age-related macular degeneration (nAMD) are not associated with interval extensions of intravitreal aflibercept 8 mg (EYLEA HD), according to a new posthoc analysis of the phase 3 PULSAR trial.¹

These results, presented at the 2024 Association for Research in Vision and Ophthalmology (ARVO) Meeting, showed more than 85% of patients with nAMD treated with aflibercept 8mg completed two years of treatment assigned to every ≥12-week dosing. Overall, disease characteristics at baseline did not predict the interval at the 96-week PULSAR endpoint.

“The findings suggest that, before starting treatment, doctors will not be able to predict the best injection interval for an individual patient, but injection intervals may be extended to longer than 4 months for many,” wrote the investigative team, led by Justus G. Garweg, Swiss Eye Institute and Berner Augenklinik.

Aflibercept 2 mg is a standard-of-care treatment for nAMD, typically given as 3 initial monthly intravitreal injections followed by an injection every 2 months.² These treatment regimens usually rely on a patient’s response and can be longer or shorter depending on the patient.

Results from the double-masked, PULSAR trial found that the higher-dose aflibercept 8 mg was non-inferior to aflibercept 2 mg in improving vision outcomes.³ Notably, aflibercept 8 mg offered the ability to extend further between injections, with every-12-week (Q12W) and every-16-week (Q16W) intervals showing non-inferiority to every-8-week (Q8W) aflibercept 2 mg in best-corrected visual acuity (BCVA) change from baseline at week 48.

According to pre-specified dose regimen modification criteria in PULSAR, intervals could be shortened to a minimum of 8 weeks in year 1 and extended to 24 weeks maximum in year 2, dependent on disease activity. For this analysis, Garweg and colleagues sought to evaluate whether the severity of nAMD before treatment could influence the time required between injections.¹

After three initial injections, participants were randomly assigned 1:1:1 to receive intravitreal aflibercept 8 mg Q12W or Q16W, or aflibercept 2 mg Q8W. Key baseline characteristics evaluated in the post hoc included BCVA, central retinal thickness (CRT), and total choroidal neovascularization (CNV) lesion area, at the 96-week mark.

Overall, 583 patients randomized to Q12W or Q16W aflibercept 8 mg regimens completed the full study treatment period. At Week 96, the BCVA increased by 5.9 letters (95% CI, 4.4 - 6.5) and the CRT had decreased by –150 µm (95% CI, –136 to –156).

Approximately 87% (n = 252) of patients initially assigned to aflibercept 8 mg Q12W were assigned to ≥Q12W dosing and 78% (n = 229) of patients initially assigned to aflibercept 8 mg Q16W were assigned to Q16W dosing.

Breaking the findings down by baseline characteristics, the mean BCVA, CRT, and CNV area, respectively, were 59.4 ± 12.8 letters, 364 ± 130 µm, and 6.1 ± 5.0 mm2 in 162 patients assigned to Q24W dosing at Week 96, 61.0 ± 13.0 letters, 352 ± 122 µm, and 6.2 ± 5.1 mm2 in 141 patients assigned to Q16W dosing, and 60.6 ± 10.6 letters, 400 ± 128 µm, and 7.1 ± 5.9 mm2 in 71 patients assigned to Q8W dosing.

Overall, based on these analytical findings, Garweg and colleagues suggested the need for dosing shorter than every 12- or 16-week intervals was not dependent on baseline characteristics in nAMD, including lesion size.

“The investigated disease characteristics at baseline were not predictive of dosing interval at Week 96,” Garweg and colleagues wrote.

References

1. _{Garweg JG, Lanzetta P, Chaudhary V, Sergio L, Machewitz T, Zhang X. Key baseline disease characteristics in nAMD are not linked to treatment interval extension of aflibercept 8 mg: A post-hoc 96-week PULSAR analysis. Paper presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Meeting, May 5–9, 2024.}
2. _{Adams BS, Sorhaitz W, Stringham J. Aflibercept. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK582136/}
3. _{Lanzetta P, Korobelnik JF, Heier JS, et al. Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial. Lancet. 2024;403(10432):1141-1152. doi:10.1016/S0140-6736(24)00063-1}