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  • Review Article
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Treat-and-extend dosing of intravitreal anti-VEGF agents in neovascular age-related macular degeneration: a meta-analysis

Eye volume 37, pages 2855–2863 (2023)Cite this article

Subjects

Abstract

Intravitreal injections of antiangiogenic agents are pivotal in treating neovascular age-related macular degeneration (nAMD). The comparative efficacy and safety of treat-and-extend (T&E) versus bimonthly, monthly, and pro re nata (PRN) dosing remains unclear. A systematic review and meta-analysis of English-language RCTs reporting on efficacy and/or safety outcomes of dosing regimens of anti-VEGF agents in nAMD was performed. Best-corrected visual acuity (BCVA, ETDRS letters) at last follow-up represented the primary endpoint, while central subfield thickness (CSFT, μm), injection burden, and ocular adverse events were secondary endpoints. A random effects meta-analysis was performed, and 95% confidence intervals were calculated. Across six RCTs, 781 T&E-, 663 monthly-, 130 PRN-, and 123 bimonthly treated eyes were included. Mean changes in BCVA and CSFT at last follow-up were similar between T&E versus monthly (WMD, –0.62 letters; 95% CI, –2.12 to 0.87; P = 0.41; WMD, 5.30 microns; 95% CI, –10.67 to 21.26; P = 0.52, respectively), bimonthly (WMD, 1.68 letters; 95% CI, –3.55 to 6.91; P = 0.53; WMD, –18.91 microns; 95% CI, –46.41 to 8.60; P = 0.18, respectively), and PRN (BCVA WMD, 1.08 letters; 95% CI, –2.95 to 5.11; P = 0.60) regimens. T&E was associated with a reduced injection burden versus monthly (WMD, –4.52 injections; 95% CI, –6.66 to 2.39; P < 0.001) but higher injection burden versus PRN (WMD, 1.81 injections; 95% CI, 1.12 to 2.51; P < 0.001) dosing. There was no significant difference in safety outcomes amongst comparators. There was no significant difference in efficacy and safety between T&E, bimonthly, monthly, and PRN dosing. T&E resulted in fewer injections versus monthly and fewer clinic visits versus PRN.

摘要

玻璃体腔内注射抗血管生成药物是新生血管性老年性黄斑变性(nAMD)非常重要的治疗方法。T&E方案与半个月给药、每月给药方案以及按需剂量 (PRN) 方案相比, 在疗效和安全性方面尚不清楚。我们对报道抗VEGF药物的治疗方案在nAMD治疗中的疗效和/或安全性评估的英文随机对照试验 (RCT) 进行了系统回顾和荟萃分析。最后一次随访的最佳矫正视力(BCVA, ETDRS字母)是主要的临床结局终点, 而视网膜中央子区厚度(CSFT, μm)、注射剂量负担和眼部不良事件是次要的结局终点。我们进行了随机效应荟萃分析, 并计算95%置信区间。在6个RCTs中, 781只眼为T&E治疗, 663只眼为每月治疗, 130只眼为PRN治疗, 123只眼为双月治疗。末次随访时, T&E方案分别与每月方案 (WMD, -0.62个字母; 95%CI, -2.12-0.87; P = 0.41; WMD, 5.30微米; 95%CI, -10.67-21.26; P = 0.52), 双月方案 (WMD, 1.68个字母; 95%CI, - 3.55 - 6.91; P = 0.53; WMD, -18.91微米; 95%CI, -46.41- 8.60; P = 0.18)和PRN方案 (BCVA WMD, 1.08个字母; 95%CI, -2.95-5.11; P = 0.60) 的BCVA和CSFT平均变化相比较均相似。 T&E方案的注射剂量负担低于每月方案(WMD, - 4.52次注射; 95%CI, -6.66-2.39; P < 0.001), 但高于PRN方案 (WMD, 1.81次; 95%CI, 1.12-2.51; P < 0.001)。比较组间安全性结果无显著差异。T&E、双月、每月和PRN给药方案之间的疗效和安全性无显著差异。与每月方案相比, T&E方案注射剂量更少; 与PRN方案相比, T&E方案的就诊次数更少。

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Acknowledgements

We thank Dr. Rufino Silva on behalf of Novartis Pharma AG for providing supplementary unpublished data from the TREND 2018 trial, Novartis Pharmaceuticals Canada Inc. for providing supplementary unpublished data from the CANTREAT 2019 trial, and Dr. Charles C. Wykoff and Hannah Yu on behalf of Genentech, Inc. for providing supplementary unpublished data from the TREX-AMD 2015 trial.

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Authors and Affiliations

  1. Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada

    Prem A. H. Nichani, Marko M. Popovic, Rajeev H. Muni & Peter J. Kertes

  2. Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Arjan S. Dhoot

  3. Institute of Biomedical Engineering, Faculty of Applied Science and Engineering, University of Toronto, Toronto, ON, Canada

    Arjan S. Dhoot

  4. Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, ON, Canada

    Ananya Pathak

  5. Department of Ophthalmology, St. Michael’s Hospital/Unity Health Toronto, Toronto, ON, Canada

    Rajeev H. Muni

  6. Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, ON, Canada

    Rajeev H. Muni & Peter J. Kertes

  7. John and Liz Tory Eye Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Peter J. Kertes

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All authors have sufficiently fulfilled the four criteria of authorship as detailed by the 2019 International Committee of Medical Journal Editors (ICMJE) Recommendations.

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Competing interests

PN, ASD, AP: None. MMP: Physicians’ Services Incorporated (PSI) Foundation (RI). RHM: Allergan (C), Bayer (C, RI), Novartis (C, RI), Roche (C). PJK: Alcon (C), Allergan (RI), ArcticDx (E), Bayer (C, RI, RP), Novartis (C, RI, RP), Novelty Nobility (C), Roche (RI). Legend: C – consultant/consulting fees; E – equity owner; S – speaker honoraria; RI – research grant/financial support (to institution); RP – research grant/financial support (personal)

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The paper is exempt from ethical committee approval given that it is a meta-analysis of previously published data as opposed to a primary study using direct/individual patient data. This research in its entirety complies with the guidelines for human studies and should include evidence that the research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki.

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Nichani, P.A.H., Popovic, M.M., Dhoot, A.S. et al. Treat-and-extend dosing of intravitreal anti-VEGF agents in neovascular age-related macular degeneration: a meta-analysis. Eye 37, 2855–2863 (2023). https://doi.org/10.1038/s41433-023-02439-6

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