Effect of key baseline disease characteristics on aflibercept 8 mg dosing interval extension: A post hoc 96-week analysis of PULSAR

Abstract

Objective Post hoc analysis of the PULSAR Phase 3 trial (NCT04423718) to describe whether dosing interval outcomes were associated with key baseline disease characteristics. Design Exploratory post hoc analysis of PULSAR, a 96-week, double-masked, active-controlled, randomized clinical trial in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) treated with aflibercept 8 mg or aflibercept 2 mg. For the main analysis, patients receiving aflibercept 8 mg were grouped according to their last assigned dosing interval at Weeks 48 and 96. Participants Patients with treatment-naïve nAMD who were randomly assigned to receive aflibercept 8 mg in PULSAR. Intervention Aflibercept 8 mg was administered every 12 weeks (8q12) or 16 weeks (8q16) following 3 initial monthly injections. Dosing intervals could be shortened in Year 1 based on prespecified disease activity criteria, whereas in Year 2, both interval shortening and extension were allowed. Patients were monitored every 4 weeks but assessed for interval modification at dosing visits only. Main Outcome Measures Baseline best-corrected visual acuity (BCVA), central retinal thickness (CRT), and macular neovascularization (MNV) area were assessed in patients grouped by their last assigned dosing interval (Q8, Q12, Q16, Q20, or Q24) at Weeks 48 and 96. Results In 86.6% and 78.4% of patients assigned to the 8q12 and 8q16 arms in PULSAR, respectively, randomized dosing intervals were maintained or extended through Week 96. In the 8q12 arm, no trends were observed in baseline BCVA, CRT, and MNV area across groups based on patients’ last assigned dosing intervals. In the 8q16 arm, no trends were observed in baseline BCVA across treatment arms; however, patients with shorter last assigned dosing intervals (Q8 and Q12) at Weeks 48 and 96 tended to have a greater baseline CRT or MNV area compared with patients with longer dosing intervals (Q16 to Q24). Conclusions Overall, findings from this PULSAR post hoc analysis of key baseline characteristics in patients grouped by dosing interval suggest that the aflibercept 8q12 and 8q16 regimens were suitable for most patients across a broad range of baseline BCVA, CRT, and MNV area values, with a large proportion of patients able to achieve and maintain extended dosing intervals through Week 96.