PULSAR: Clinical Outcomes of Aflibercept 8 mg with Extended Dosing and 2 mg in Neovascular Age-Related Macular Degeneration in Subgroups Defined by Baseline Characteristics

Objective To evaluate the impact of baseline disease severity on clinical outcomes with aflibercept 8 mg with extended dosing intervals versus aflibercept 2 mg in patients with treatment-naïve neovascular age-related macular degeneration. Design Post hoc descriptive subgroup analysis of PULSAR (NCT04423718), a 96-week, double-masked, randomized, active-controlled clinical trial investigating treatment of neovascular age-related macular degeneration with aflibercept 8 mg at extended dosing intervals or aflibercept 2 mg every 8 weeks. Patients were subgrouped according to the severity of baseline disease characteristics, namely best-corrected visual acuity, central retinal thickness, choroidal neovascularization (CNV) lesion type, and CNV area. Participants Patients with neovascular age-related macular degeneration were randomly assigned to receive aflibercept 8 or 2 mg. Overall, 869 patients completed treatment through week 96. Intervention Aflibercept 8 mg was administered every 12 or 16 weeks (8q12 or 8q16) after 3 initial monthly injections. Dosing intervals could be shortened in years 1 and 2 and extended in year 2 based on prespecified disease activity criteria. Aflibercept 2 mg every 8 weeks was administered after 3 initial monthly injections. Main Outcome Measures Best-corrected visual acuity and central retinal thickness outcomes among subgroups defined by baseline best-corrected visual acuity (≤54, 55–73, and ≥74 ETDRS letters), central retinal thickness (≤278, 279–343, 344–422, and ≥423 μm), CNV lesion type (minimally classic, occult only, and predominantly classic), and CNV area (<1.3, 1.3–<4, 4–<5, and ≥5 mm²). The last assigned dosing interval at week 96 for the aflibercept 8q12 and 8q16 treatment arms was also analyzed by disease severity. Results Patients in the aflibercept 8q12 and 8q16 arms achieved visual and anatomic outcomes at week 96 comparable to those in the aflibercept 2q8 arm within subgroups defined by baseline disease severity. Most patients randomized to the 8q12 and 8q16 arms in each subgroup defined by baseline disease severity had last assigned dosing intervals of ≥12 and ≥16 weeks, respectively, at week 96. Conclusions Treatment with aflibercept 8 mg can achieve the functional and anatomic benefits observed with aflibercept 2 mg, but with prolonged dosing intervals, regardless of disease severity at initiation. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.