IVT Aflibercept 2mg in nAMD: XTEND at 3 years
Reviewed by Sofia Rokerya

This study investigated the long-term, effectiveness and safety of IVT-AFL 2mg for neovascular age-related macular degeneration (nAMD). XTEND was a multicentre, observational, prospective study, which was conducted across 127 centres across 17 countries with a follow-up period of 36 months. Treatment-naïve patients were treated with IVT-AFL 2mg (fixed dosing or treat-and extend (T&E) treatment). Patients were treated according to the nationally approved label, standards of care, and judgment of the treating physician. Intervals could be extended according to either of the 2 national labels. In European Medicines Agency (EMA)-aligned (minimum treatment interval of 8 weeks in year 1 after 3 initial monthly IVTAFL 2mg injections) and a maximum treatment interval of 16 weeks, here the treatment intervals could be extended by 2–4-weeks. In the non-EMA-aligned, there was minimum treatment interval of 4 weeks in year 1 after 3 initial monthly IVTAFL 2mg injections and a maximum treatment interval of 12 weeks. The non-EMA-label treatment intervals could be extended in up to 4-weekly increments. In total, 1483 patients were treated with IVT-AFL 2mg; mean ± standard deviation (SD) age was 78.8 ±8.5 years; 60.4% were female. Overall, 62.6% of patients completed the 36-month follow-up visit. The mean (95% confidence interval (CI)) changes in best corrected visual acuity (BCVA) from baseline were +4.6 (3.7, 5.4), +2.3 (1.3, 3.3), and +0.9 (−0.2, 1.9) at months 12, 24, and 36, respectively. The mean (95% CI) changes in central subfield thickness (CST) from baseline were -106 (-114, -99)μm, -109 (-117, -102)μm, and -110 (-118, -103)μm at months 12, 24 and 36, respectively. The mean ± SD numbers of injections from baseline to months 12, 24, and 36 were 7.7 ±2.7, 11.3 ±5.3, and 13.7 ±7.5, respectively. The proportion of all patients who achieved ≥5-letter, >10 letters and ≥15-letter visual acuity gains by month 36 were 47%, 34% and 22%, respectively. The mean baseline CST was similar across both labels. The results show that a high proportion of patients (81%) maintained visual improvements (lost fewer than 15 letters) and that anatomic improvements from baseline were maintained over the 36-month period, even though the study was conducted, in part, during the Covid-19 pandemic. For the overall global population, initial improvements in BCVA were observed at month 12 (+4.6 letters), and vision was subsequently maintained close to baseline vision through month 36 (+0.9 letters), suggesting that long-term durability of vision is achievable with IVT- AFL 2mg in patients with nAMD. Patients received approximately half of all IVT-AFL 2mg injections in the first 12 months as expected following guidance from the labels, with injection frequency reducing thereafter through to 36 months, to a mean of 13.7 injections overall. Findings from this 36-month analysis of the real-world, global XTEND study demonstrated that proactive treatment with IVT-AFL 2mg led to meaningful improvements in BCVA and CST. No safety concerns were identified. Strengths: Prospective design, real world evidence with inclusion of a large, heterogenous patient population from 17 countries. Limitations: observational design with challenges due to discontinuation and poor attendance. Additionally, it is not possible to confirm that the treatment strategy was followed accurately by all physicians. The OCT measurements were not standardised over all centres. Missing data due to non-adherence and non-attendance could be another pitfall.

Aflibercept 2 mg for neovascular age-related macular degeneration: XTEND at 3 Years. 
Korobelnik JF, Chaudhary V, Mitchell P, et al.
OPHTHALMOLOGICA
2025;1–13: DOI: 10.1159/000549663 [ePub ahead of print].