Introduction

The CANDELA and PULSAR trials demonstrated the efficacy and safety of intravitreal aflibercept 8 mg in the treatment of neovascular age-related macular degeneration (nAMD) [1, 2]. SPECTRUM is the first global real-world study of aflibercept 8 mg in nAMD, and its unique study design enables rolling global and country cohort analyses. Here, we describe early clinical experience in the first ~100 patients with treatment-naïve (TN) or previously treated (PT) nAMD to have a visit and visual acuity (VA) assessment at Week 8 (W8) in SPECTRUM.

Methods

SPECTRUM (NCT06075147) is a 24-month, prospective observational study (February 2024–September 2027) being conducted across 18 countries among patients with TN or PT nAMD aged ≥50 years who have been prescribed aflibercept 8 mg by their attending physician. All treatment decisions are made by each patient’s physician in accordance with local clinical practice. Enrollment criteria are reported in the ClinicalTrials.gov record [3]. The study protocol was approved by each study site’s independent ethics committee/institutional review board. All participants provided written informed consent. The W8 analysis described here was prespecified; all data were analysed descriptively.

Results

Baseline characteristics are shown in Table 1. Patients received a mean ± SD (median) of 3.0 ± 0.3 (3) and 2.6 ± 0.6 (3) injections until Day 70 after baseline in the TN and PT nAMD cohorts, respectively (first injection received at baseline). In the TN and PT nAMD cohorts, mean (95% CI) change in VA from baseline at W8 was +3.2 (1.2, 5.1) and 0.0 (−1.6, 1.6) letters, respectively (Fig. 1A), and mean change in central retinal thickness was −115 (−141, −89) and −39 (−60, −19) µm, respectively (Fig. 1B). The proportions of patients without intraretinal fluid or subretinal fluid increased from baseline to W8 in both cohorts (Fig. 1C). Note that the W8 injection data include any injections received at W8, whereas the W8 outcomes reflect the injections administered before the W8 visit.

Fig. 1: Functional and anatomic outcomes in patients with nAMD at Week 8 in SPECTRUM.
figure 1

A Mean change in VA from baseline at Week 8. B Mean change in CRT from baseline at Week 8. C Proportion of patients without intraretinal fluid or subretinal fluid at Week 8. Data are for the FAS (observed cases); error bars represent 95% CI. Mean VA/CRT change at Week 4 and Week 8 from baseline was calculated in patients with a VA/CRT assessment at Week 4 and Week 8, respectively. Week 4 = visits closest to 28 (14–42) days after the first injection (BL), and Week 8 = visits closest to 56 (43–70) days after BL. Note that outcomes described here would not reflect the effect of an injection received at Week 8, and some patients may not have received an injection at this timepoint. BL baseline, CRT central retinal thickness, ETDRS Early Treatment Diabetic Retinopathy Study, FAS full analysis set (all patients receiving ≥1 dose of study drug plus ≥1 post-baseline assessment), nAMD neovascular age-related macular degeneration, PT previously treated, TN treatment-naïve, VA visual acuity, W week. aFluid data were collected per investigator discretion; the presence of intraretinal fluid and subretinal fluid was determined by optical coherence tomography with the instrument available at each study site, and the proportions presented here were calculated based on the number of patients who had an assessment at each of the indicated timepoints.

Full size image
Table 1 Baseline demographics and disease characteristics of patients in the SPECTRUM Week 8 analysis of the treatment-naïve and previously treated nAMD cohorts.
Full size table

In the TN and PT nAMD cohorts, ocular treatment-emergent adverse events (TEAEs) in the study eye occurred in 3/114 (2.6%) and 4/104 (3.9%) patients, respectively, and non-ocular TEAEs were observed in 5/114 (4.4%) and 0 patients, respectively. Two ocular TEAEs in the PT nAMD cohort were considered study drug–related (increased intraocular pressure and vitreous floaters; n = 1 each). There were no serious ocular or non-ocular TEAEs in either cohort, nor any cases of intraocular inflammation.

Discussion

This prespecified W8 analysis of the SPECTRUM study provides valuable insights into early treatment responses to aflibercept 8 mg in diverse real-world settings among clinically heterogenous patients with nAMD. Patients received their first injection at baseline; by the W8 visit, the TN nAMD cohort reported VA gains, and both the TN and PT nAMD cohorts reported improvements in CRT and absence of fluid. The safety profile was consistent with that reported for the PULSAR trial [1].

SPECTRUM is an observational study, and analyses are exploratory only. Findings from this W8 analysis are based on ~100 patients only in each cohort, and this patient subset may not be fully reflective of the overall global SPECTRUM nAMD cohorts.