UCL Institute of Ophthalmology, London, UK.
NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Sci Rep. 2020 Oct 5;10(1):16499. doi: 10.1038/s41598-020-73571-6.
New clinical trials for diabetic macular oedema (DMO) are being designed to prove superiority over aflibercept when this agent is already very effective in improving visual acuity (VA) and DMO. The aim of this study was to determine the optimal inclusion-exclusion criteria for trials to aim for superiority in visual outcomes with newer agents. As Phase 1 studies are short duration, we aimed to evaluate the early response of aflibercept in a real-world cohort initiated on monthly aflibercept for 3 consecutive injections and observed the effects at 4 months. The sub-optimal responders were pre-defined based on different cut-offs for VA and central sub-field thickness (CST). 200 patients with treatment naïve DMO treated with 3 loading doses of aflibercept were included in the study. We found that those presenting with baseline VA of 35-54 ETDRS letters (n = 43) had higher proportion of sub-optimal responders compared to other categories (p < 0.001). Patients with baseline CST of less than 400 µm (n = 96) responded less well functionally and anatomically to loading dose than eyes with baseline CST of 400 µm or more (n = 104, p = 0.02), indicating that eyes with CST ≥ 400 µm is another inclusion criteria. There was minimal correlation between change in CST and change in VA at 4 months (r = - 0.27), suggesting that both these inclusion criteria are non-exclusive. However, for maximal efficacy, patients that meet both these inclusion criteria are more likely to show benefit from an alternative intervention. New trials should aim to include patients with treatment naïve DMO with VA between 35-54 letters and CST of 400 µm or more when aflibercept is used as the comparator.
新的糖尿病黄斑水肿 (DMO) 临床试验旨在证明与 aflibercept 相比具有优越性，因为 aflibercept 已经非常有效地提高了视力 (VA) 和 DMO。本研究旨在确定旨在通过新型药物获得更好视觉结局的临床试验的最佳纳入排除标准。由于 I 期研究持续时间较短，我们旨在评估 aflibercept 在现实世界队列中的早期反应，该队列连续 3 个月每月接受 aflibercept 治疗，并在 4 个月时观察效果。根据 VA 和中央子场厚度 (CST) 的不同截止值，预先定义了亚最佳反应者。该研究纳入了 200 名接受 3 个负荷剂量 aflibercept 治疗的初治 DMO 患者。我们发现，基线 VA 为 35-54 ETDRS 字母的患者（n = 43）与其他类别相比，亚最佳反应者的比例更高（p < 0.001）。基线 CST 小于 400 µm 的患者（n = 96）在功能和解剖上对负荷剂量的反应不如基线 CST 为 400 µm 或更高的患者（n = 104，p = 0.02），表明 CST ≥ 400 µm 的患者是另一个纳入标准。4 个月时 CST 的变化与 VA 的变化之间几乎没有相关性（r = -0.27），这表明这两个纳入标准不是排他性的。然而，为了获得最大疗效，符合这两个纳入标准的患者更有可能从替代干预中获益。新的临床试验应旨在纳入基线 VA 在 35-54 字母之间且 CST 为 400 µm 或更高的初治 DMO 患者，当 aflibercept 用作比较剂时。
