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Impact of treat and extend criteria on proportions that can be extended after loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration: PRECISE Report 5

Eye (2024)Cite this article

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Abstract

Objective

To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD).

Methods

Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response. The proportion of patients that qualify for interval extension based on different clinical trial criteria was also evaluated.

Results

A total of 722 patients with visual acuity (VA) and optical coherence tomography (OCT) scans done at all 4 visits were included. Of these 32.4% of eyes responded with complete macular fluid resolution after the first injection with no recurrence through the loading phase (super-responders) while 26.9% had persistent macular fluid in all 4 visits (true non-responders). The rest were considered suboptimal responders. Change in VA showed marked variations within each of these categories of fluid resolution. For extension of next treatment interval, if presence of any macular fluid at the post-loading visit is the only criteria considered, about 50% could be extended to 8 weeks. If both VA worsening by ≥5 letters and a > 25 μm increase in central sub-field thickness (CST) are considered, 90% will be eligible for interval extension.

Conclusion

Clinical trial designs and pre-defined treatment extension/shortening criteria determine the proportion of patients requiring treatment in the post-loading visit. The short and long-term impact of interval extension immediate post-loading on visual outcome in clinical practice is unknown.

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Data availability

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.

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Funding

The investigator-initiated study was funded by Boehringer Ingelheim International GmbH (Grant number: SIVS1045). This study was also supported by the NIHR Biomedical Research Centre and Clinical Research Facility at the Moorfields Eye Hospital National Health Service Foundation Trust and the University College London Institute of Ophthalmology. Boehringer Ingelheim reviewed and approved submission of the manuscript. Benjamin Burton has been on advisory boards and received international conference attendance sponsored by Novartis, Roche and Bayer. Geeta Menon has conducted consultancy-advisory boards for Novartis, Bayer and Allergan, received educational travel grants from Novartis, Bayer, Allergan. Ian Pearce has received lecture fees from Allergan, Bayer, Roche, Heidelberg and Novartis, consultancy fees from Allergan, Alimera, Bayer and Novartis and travel fees from Allergan, Bayer and Novartis. Faruque Ghanchi has received honorarium for consultancy-advisory boards from Alimera, Allergan, Bayer, Novartis, Oxford Bioelectronics, Roche, educational travel grants from Allergan, Bayer, Novartis. Faruque Ghanchi is a section editor of EYE. Martin McKibbin has received consultancy, lecture or advisory board honoraria from Bayer, Novartis and Riche and educational travel grants from Bayer, Novartis and Roche. Praveen J. Patel has received lecture and advisory board honoraria from Bayer, Novartis and Roche and educational travel grants from Bayer and Roche. Richard Gale has conducted consultancy-advisory boards for Novartis, Bayer, Biogen, Boehringer Ingelheim and Allergan, Alimera, Santen, received educational travel grants from Novartis, Bayer, Allergan, Heidelberg Engineering. James Talks is a consultant for Bayer and Roche, received grant support from Bayer, Novartis and Heidelberg Engineering, and is involved in research for Allergan, Alimera, Roche, Bayer, Novartis and Boehringer-Ingelheim. Ajay Kotagiri received travel support from Novartis, Bayer, and Allergan, and speaker fees from Allergan and Bayer. Shruti Chandra received travel support from Boehringer Ingelheim and is an editorial board member of EYE. Sivaprasad reported receiving financial support from AbbVie, Amgen, Apellis, Bayer, Biogen, Boehringer Ingelheim, Novartis, Eyebiotech, Eyepoint Pharmaceuticals, Janssen Pharmaceuticals, Nova Nordisk, Optos, Ocular Therapeutix, Kriya Therapeutics, OcuTerra, Roche, Stealth Biotherapeutics and Sanofi. Sobha Sivaprasad is the Editor-in-Chief of EYE.

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Authors and Affiliations

  1. National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK

    Sridevi Thottarath, Sarega Gurudas, Swati Chandak, Praveen J. Patel, Eleni Karatsai, Shruti Chandra & Sobha Sivaprasad

  2. Institute of Ophthalmology, University College London, London, UK

    Sarega Gurudas, Shruti Chandra & Sobha Sivaprasad

  3. South Tyneside and Sunderland NHS Foundation Trust, Sunderland, UK

    Ajay Kotagiri

  4. The Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust, Liverpool, UK

    Ian Pearce

  5. Leeds Teaching Hospitals NHS Trust, Leeds, UK

    Martin McKibbin

  6. Frimley Health NHS Foundation Trust, Surrey, UK

    Geeta Menon

  7. James Paget University Hospitals NHS Foundation Trust, Norfolk, UK

    Benjamin J. L. Burton

  8. Newcastle Hospitals NHS Foundation Trust, Newcastle, UK

    James Talks

  9. King’s College Hospital NHS Foundation Trust, London, UK

    Anna Grabowska

  10. Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK

    Faruque Ghanchi

  11. Hull York Medical School and York, University of York and Scarborough Teaching Hospital NHS Foundation Trust, York, UK

    Richard Gale

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  1. Sridevi Thottarath
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Contributions

Conceptualization: S.T. and S.S.; Data curation: Sh.C., S.T., E.K. and S.C.; Formal analysis: S. T, S.G. and S.S.; Funding acquisition: S.S.; Methodology: S.T, S.G. and S.S; Project administration: S.S.; Resources: S.T., G.M., B.J.B., I.P., M.M., Sh.C., S.C., A.K., J.T., A.G., F.G., R.G., L.K. and S.S.; Supervision: An.G., S.S.; Visualization: S.G. and S.T.; Writing – original draft: S.T, S.G. and S.S.; Writing - review & editing: S.S. Review and approval of final manuscript: S.T., S.G., An.G., S.S, P.J.P., G.M., B.J.B., I.P., M.M., S.T.,S.C., A.K., J.T., F.G., R.G. and E.K.

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Correspondence to Sobha Sivaprasad.

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Thottarath, S., Gurudas, S., Chandak, S. et al. Impact of treat and extend criteria on proportions that can be extended after loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration: PRECISE Report 5. Eye (2024). https://doi.org/10.1038/s41433-024-03110-4

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  • DOI: https://doi.org/10.1038/s41433-024-03110-4

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