One-Year and 18-Month Outcomes in nAMD Patient Eyes Switched to Brolucizumab Alone versus to Brolucizumab Alternating with Other Anti-VEGF Agents

Abstract

Objective

Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF.

Methods

The overall study population comprised eyes that were given ≥1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with ≥3 brolucizumab injections over ≥12 or ≥18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with ≥2 brolucizumab injections and ≥1 other anti-VEGF over ≥12 or ≥18 months.

Results

A total of 482 eyes received ≥1 brolucizumab injection during the study period. Mean VA changes from baseline were −1.1±15.1 letters (BRO cohort; n = 174) and 1.3±13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0±13.5 letters (BRO cohort; n = 95) and −7.3±17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9±48.1 days (BRO cohort) and +11.1±17.3 days (ALT cohort) at Month 12 and +36.3±52.3 days (BRO cohort) and +14.0±19.9 days (ALT cohort) at Month 18. Mean changes in CMT were −35.2±108.1 μm (BRO cohort) and −31.5±91.2 μm (ALT cohort) at Month 12 and −38.9±75.0 μm (BRO cohort) and −9.0±59.9 μm (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes.

Conclusion

Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD.

Keywords:

• alternating anti-VEGF treatments
• brolucizumab
• neovascular age-related macular degeneration
• wet age-related macular degeneration
• 12-month outcomes
• 18-month outcomes

Abbreviations

AE, adverse event; ALT, alternating cohort; BRO, brolucizumab; CI, confidence interval; CMT, central macular thickness; ETDRS, Early Treatment Diabetic Retinopathy Study; IOI, intraocular inflammation; logMAR, logarithm of the minimum angle of resolution; nAMD, neovascular age-related macular degeneration; OCT, optical coherence tomography; RO, retinal vascular occlusion; RV, retinal vasculitis; SD, standard deviation; VA, visual acuity; VEGF, vascular endothelial growth factor.

Data Sharing Statement

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the program in line with applicable laws and regulations.

Ethics Statement

This study was granted a Waiver Of Authorization by Sterling IRB (IRB ID 9558).

Acknowledgments

The authors wish to thank the following from Retina Associates of Cleveland Inc.: Dr Arnold F. Nothnagel and Dr Thomas J Tsai, as well as Tia Drugan for retrieving CMT data from RACI locations. Support was also provided by Novartis Ireland Ltd. employees Ver Bilano, PhD (analytical support), Andrew Heaney, PhD (double programming). Medical writing assistance, under the guidance of the authors, was provided by Stefan Amisten, PhD and Susan Simpson, PhD (both Novartis Ireland Ltd.), in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). Medical writing support was funded by Novartis Pharma AG.

The Association for Research in Vision and Ophthalmology (ARVO) May 1–4, 2022, Denver, CO, USA.

Disclosure

NS and HK are Novartis employees and HK is a Novartis shareholder. SBS was a Novartis employee at the time of this study and is a current employee of the Novartis Sandoz division. LZ is an employee of KMK Consulting, which was paid by Novartis to conduct the statistical analysis of the study. JMC has received grants from Aerpio, Alcon Laboratories, Alimera Sciences, Allergan/AbbVie, Apellis, Genentech, Hoffman La Roche, MacTel, National Eye Institute, Novartis, Regeneron and RegenexBio, consulting fees from Alimera Sciences, Apellis and RegenexBio, honoraria from Alimera Sciences, Allergan/AbbVie, Apellis, Genentech, Iveric Bio, Novartis, Regeneron and RegenexBio. DM reports consultancy fees and Speakers’ Bureau honoraria from Regeneron Pharmaceuticals. LS has received grants from Alkeus, Apellis, Genentech, Ionis Pharm, NGM, Biopharmaceuticals, Graybug Vision and Kodiak Sciences. The authors report no other conflicts of interest in this work.

Additional information

Funding

Financial support was provided by Novartis Pharma AG (Basel, Switzerland). The sponsor or funding organization participated in the design of the study; management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript.