XTEND: Proactive Aflibercept Achieves Functional Improvements in Treatment-Naive AMD

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Two-year XTEND trial data shows proactive aflibercept led to meaningful functional and anatomic improvements that were maintained across the study period.

Two-year results from the global XTEND trial revealed a proactive intravitreal aflibercept treatment regimen achieved meaningful functional and anatomic improvements among eyes with neovascular age-related macular degeneration (nAMD).1

The XTEND trial obtained global real-world data on proactive regimens of intravitreal aflibercept among treatment-naive eyes in routine clinical practice and during the COVID-19 pandemic across 127 medical centers. In XTEND, a proactive intravitreal aflibercept regimen increased the proportion of nAMD eyes achieving ≥70 ETDRS letters, while those with baseline BCVA ≥70 ETDRS letters maintained their vision, at 24 months.

“The strengths of XTEND include the prospective design, long-term study duration, and the large heterogeneous population enrolled from 127 centers across 17 countries, with a mean age of patients (78.7 years) that is reflective of patients with nAMD seen in routine clinical practice,” wrote the investigative team, led by Jean-Francois Korobelnik, MD, PhD, Service d’Ophtalmologie, CHU Bordeaux.

Outcomes reported in anti-VEGF randomized controlled trials often do not translate to regular clinical practice, with patients receiving fewer injections and achieving worse visual acuity gains than in a controlled environment.2 As such, observational studies can provide more insight into the treatment patterns and their effectiveness in heterogeneous populations, to fill in the gap between trials and real-world experience.

XTEND collected real-world evidence after a label update to include a treat-and-extend regimen, with extensions of 2- to 4-weekly increments to a maximum of 12 or 16 weeks, according to the label.1 The study used two intravitreal aflibercept labels approved for AMD, including the European Medicines Agency (EMA)-aligned label, with a minimum interval of 8 weeks, and the non-EMA-aligned label, with a minimum interval of 4 weeks, for the first year.3

Treatment-naive patients with nAMD were eligible for XTEND and received a fixed-dosing or treat-and-extend regimen of proactive intravitreal aflibercept, per the judgment of the treating physician.1 The investigative team assessed the mean change in BCVA from baseline to month 12 and month 24, as well as changes in CST in the same period, and stratified by baseline factors. Additional sensitivity analyses were performed for the COVID-19 pandemic, as it began after the initiation of XTEND.

At the 24-month XTEND analysis, the trial had enrolled 1561 patients from 127 centers in 17 countries. Patients had a mean age of 78.7 years, 891 patients (60.8%) were female, and the baseline BCVA and CST measures were 54.3 ± 20.3 ETDRS letters and 374 ± 126 µm, respectively. Among the study participants, 1466 patients (93.9%) were included in the full analysis set, including 1165 (79.5%) patients in the EMA-aligned group and 301 (20.5%) patients in the non-EMA-aligned group.

Upon analysis, investigators found the mean change in BCVA from baseline was +4.3 letters at month 12 and +2.3 letters at month 24. Among this cohort, a total of 1263 patients (86.2%) maintained vision (lost ≤15 letters) – meanwhile, the proportion of patients with BCVA ≥70 letters was 28.1% at baseline and increased to 41.5% at month 24.

Stratification by treatment regimen revealed those receiving the treat-and-extend regimen had a mean BCVA gain of +2.6 letters at month 24, while those on the fixed-dosing regimen had a mean BCVA gain of 0.0 letters. Anatomic outcomes showed the mean change in CST from baseline was –106 µm at month 12 and –109 µm at month 24. The changes at month 24 were numerically similar in both label groups, according to investigators.

Analyses of the COVID-19 pandemic’s impact showed the COVID-19 treatment cohort experienced a numerically higher change in BCVA (+2.4 letters), while mean changes in CST from baseline were numerically similar for the pre-COVID-19 treatment cohort (–107 µm) and the COVID-19 treatment cohort (–109 µm) at month 24.

Korobelnik and colleagues noted the study provides new insight into the impact of routine clinical practice on the use of different labels worldwide. The analysis revealed a similar number of patients with a last completed interval of ≥12 weeks for both the EMA-aligned and non-EMA-aligned label group by 24 months, but a slightly higher number of injections in the non-EMA-aligned group.

“While similar treatment patterns were observed, the results must be interpreted with caution due to variations from the labels (e.g., shorter treatment intervals), variations from the intended treatment regimen (fixed or treat-and-extend), and the variable impact that the COVID-19 pandemic had on healthcare systems,” investigators wrote.


  1. Korobelnik JF, Chaudhary V, Mitchell P, et al. XTEND: Two-Year Results from a Global Observational Study Investigating Proactive Dosing of Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration. Ophthalmol Ther. Published online January 10, 2024. doi:10.1007/s40123-023-00867-x
  2. Okada M, Wong TY, Mitchell P et al. Defining nonadherence and nonpersistence to anti-vascular endothelial growth factor therapies in neovascular age-related macular degeneration. JAMA Ophthalmol. 2021;139(7):769–76.
  3. European Medicines Agency. Eylea (Aflibercept). Summary of product characteristics. [updated January 2023; cited May 2023]