TY - JOUR
T1 - Early Residual Fluid-Free Status and Long-Term BCVA Outcomes
T2 - A Treatment Agnostic, Post Hoc Analysis of Pooled HAWK and HARRIER Data
AU - Jhaveri, Chirag
AU - Wykoff, Charles C.
AU - Khanani, Arshad M.
AU - Eandi, Chiara M.
AU - Chang, Andrew
AU - B, Guruprasad
AU - Gedif, Kinfemichael A.
AU - Singer, Michael
N1 - Funding Information:
Funding/Support: 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; and preparation, review, and approval of the manuscript. Financial Disclosures: C.J. reports Consultant fees from Novartis; Research support from DRCR Retina Network, Genentech, Gyroscope, Novartis, Regeneron, and RegenxBio. C.C.W. reports Consulting to the following: Adverum, Aerie Pharmaceuticals, Allergan, Apellis, Arctic Vision, Arrowhead Pharmaceuticals, Bausch + Lomb, Bayer, Bionic Vision Technologies, Chengdu Kanghong Biotechnologies (KHB), Clearside Biomedical, EyePoint Pharmaceuticals, Genentech, Gyroscope, IVERIC Bio, Kato Pharmaceuticals, Kodiak Sciences, NGM Biopharmaceuticals, Novartis, OccuRx, Ocular Therapeutix, ONL Therapeutics, Opthea Limited, Oxurion, Palatin, PolyPhotonix, RecensMedical, Regeneron, RegenXBio, Roche, SAI MedPartners, Takeda, and Verana Health. Research: Adverum, Aerie Pharmaceuticals, Aldeyra, Alimera Sciences, Allergan, Amgen, Apellis, Asclepix, Bayer, Boehringer Ingelheim, Chengdu Kanghong Biotechnology, Clearside Biomedical, Gemini, Genentech, Graybug Vision, Gyroscope, IONIS Pharmaceutical, iRENIX, IVERIC bio, Kodiak Sciences, LMRI, Neurotech Pharmaceuticals, NGM Biopharmaceuticals, Novartis, Oxurion, RecensMedical, Regeneron, RegenXBio, Roche, SamChunDang Pharm, Taiwan Liposome Company, and Xbrane BioPharma. Ownership/stock: ONL Therapeutics, PolyPhotonix, RecensMedical, and Visgenx. A.M.K. reports Consultant fees from Adverum, Aerpio, Alcon, Allergan, 4DMT, Broadwing Bio, Dutch Ophthalmic Research Center, Genentech, Inc. Iveric Bio, Kato Pharmaceuticals, Kodiak Sciences Inc. Novartis, Gemini Therapeutics, Graybug, Gyroscope, Opthea, Oxurion, PolyPhotonix, Recens Medical, Regenxbio; Research support from Adverum, Alkahest, Allergan, Allegro, Gemini Therapeutics, Genentech, Inc. Gyroscope, Iveric Bio, NGM Pharmaceuticals, Kodiak Sciences Inc. Novartis, Opthea, Ophthotech, Oxurion, Regenxbio, and Recens Medical, Surrozen; and lecture fees from Allergan, Genentech, and Novartis. C.M.E. reports Consultant fees from Bayer, Novartis, and Roche; lecture fees from Allergan, Bayer, and Novartis. A.C. reports Consultant fees from Alcon, Allergan, Bayer, Novartis, and Roche. Research support from Allergan, Novartis, and Bayer. G.B. and K.A.G. are employees of Novartis Pharmaceuticals Corporation and hold Novartis stock options. M.S. reports Consulting fee: Aerie, Allegro, Allergan, Genentech, Kodiak, Novartis, Regeneron, Santen, Eyepoint, Alimera. Speakers Bureau: Allergan, Genentech, Mallinckrodt, Novartis, Regeneron, Spark. Contracted research: Aerie, Allegro, Allergan, DRCR, Genentech, Icon, Ionis, Kalvista, Kodiak, Novartis, Opthea, Optos, Regeneron, Santen, Senju, Sydnexis, and Ribomic. Equity: Aviceda, Nanoscope, Inflammasome. All authors attest that they meet the current ICMJE criteria for authorship. Acknowledgment: The authors thank Caroline Herbert (Bedrock Healthcare Communications, UK), for assistance with medical writing (funded by Novartis Pharma AG).
Funding Information:
Acknowledgment: The authors thank Caroline Herbert (Bedrock Healthcare Communications, UK), for assistance with medical writing (funded by Novartis Pharma AG).
Publisher Copyright:
© 2021 The Authors
PY - 2022/4
Y1 - 2022/4
N2 - Purpose: The aim of this study was to determine associations between early residual fluid (ERF)−free status and improved long-term visual outcomes. Design: This was a retrospective clinical cohort study from a post hoc analysis of 2 phase III clinical trials’ data. Methods: Independent of treatment allocation, patients from the multicenter, prospective, randomized, double-masked HAWK and HARRIER trials who received either brolucizumab 6 mg or aflibercept 2 mg were split into 2 cohorts depending on the presence or absence of ERF at week 12. In addition, similar analyses were performed on the presence or absence of early residual intraretinal fluid (IRF) and subretinal fluid (SRF) at week 12. The 2 groups, ERF-free (n = 1051) and ERF (n = 366) patients were compared. Changes from baseline in best corrected visual acuity (BCVA) and central subfield thickness (CST) were determined. Results: From week 12 to 96, patients who were ERF free had greater least squares (LS) mean increases from baseline for BCVA and CST compared to ERF patients. Greater LS mean differences in BCVA from week 12 to 96 were noted between ERF-free and ERF patients. A greater proportion of patients in the ERF-free cohort reported a ≥5, ≥10, or ≥15 letter improvement, and a higher proportion reported BCVA ≥70 letters from baseline to week 96 compared to patients with fluid. Conclusions: Improvements in visual outcomes in ERF-free patients were greater than in ERF patients occurring as early as 4 weeks (week 12) after the last loading dose and continued to week 96. Therefore, ERF status may be a useful indicator of anti−vascular endothelial growth factor treatment response.
AB - Purpose: The aim of this study was to determine associations between early residual fluid (ERF)−free status and improved long-term visual outcomes. Design: This was a retrospective clinical cohort study from a post hoc analysis of 2 phase III clinical trials’ data. Methods: Independent of treatment allocation, patients from the multicenter, prospective, randomized, double-masked HAWK and HARRIER trials who received either brolucizumab 6 mg or aflibercept 2 mg were split into 2 cohorts depending on the presence or absence of ERF at week 12. In addition, similar analyses were performed on the presence or absence of early residual intraretinal fluid (IRF) and subretinal fluid (SRF) at week 12. The 2 groups, ERF-free (n = 1051) and ERF (n = 366) patients were compared. Changes from baseline in best corrected visual acuity (BCVA) and central subfield thickness (CST) were determined. Results: From week 12 to 96, patients who were ERF free had greater least squares (LS) mean increases from baseline for BCVA and CST compared to ERF patients. Greater LS mean differences in BCVA from week 12 to 96 were noted between ERF-free and ERF patients. A greater proportion of patients in the ERF-free cohort reported a ≥5, ≥10, or ≥15 letter improvement, and a higher proportion reported BCVA ≥70 letters from baseline to week 96 compared to patients with fluid. Conclusions: Improvements in visual outcomes in ERF-free patients were greater than in ERF patients occurring as early as 4 weeks (week 12) after the last loading dose and continued to week 96. Therefore, ERF status may be a useful indicator of anti−vascular endothelial growth factor treatment response.
KW - Angiogenesis Inhibitors/therapeutic use
KW - Clinical Trials, Phase III as Topic
KW - Cohort Studies
KW - Humans
KW - Intravitreal Injections
KW - Multicenter Studies as Topic
KW - Prospective Studies
KW - Randomized Controlled Trials as Topic
KW - Ranibizumab/therapeutic use
KW - Receptors, Vascular Endothelial Growth Factor/therapeutic use
KW - Retrospective Studies
KW - Tomography, Optical Coherence
KW - Treatment Outcome
KW - Vascular Endothelial Growth Factor A
KW - Visual Acuity
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U2 - 10.1016/j.ajo.2021.10.017
DO - 10.1016/j.ajo.2021.10.017
M3 - Article
C2 - 34695400
AN - SCOPUS:85121339256
SN - 0002-9394
VL - 236
SP - 12
EP - 19
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
ER -