TY - JOUR
T1 - INTRAVITREAL NESVACUMAB (ANTIANGIOPOIETIN 2) PLUS AFLIBERCEPT in DIABETIC MACULAR EDEMA
T2 - Phase 2 RUBY Randomized Trial
AU - Brown, David M.
AU - Boyer, David S.
AU - Csaky, Karl
AU - Vitti, Robert
AU - Perlee, Lorah
AU - Chu, Karen W.
AU - Asmus, Friedrich
AU - Leal, Sergio
AU - Zeitz, Oliver
AU - Cheng, Yenchieh
AU - Schmelter, Thomas
AU - Heier, Jeffrey S.
N1 - Funding Information:
The authors thank the study investigators and patients involved in this study. Medical writing support was provided by Tiffany DeSimone, PhD, and Nila Bhana, MSc, of Prime (Knutsford, United Kingdom), in accordance with the Good Publication Practice guidelines ( Link ), and funded by Regeneron Pharmaceuticals, Inc. The authors were involved in the study design and collection, analysis, and interpretation of data. All authors had full access to all the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.
Funding Information:
The RUBY study was funded by Regeneron Pharmaceuticals, Inc., Tarrytown, New York, and Bayer HealthCare, Berlin, Germany. The sponsors participated in the design and conduct of the study, analysis of the data, and preparation of the manuscript.
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - PURPOSE: The purpose of this study was to compare intravitreal nesvacumab (anti-angiopoietin 2) plus aflibercept with intravitreal aflibercept injection (IAI) in diabetic macular edema.METHODS: The eyes (n = 302) were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, Weeks 4 and 8. LD combo continued every 8 weeks (q8w). HD combo was rerandomized at Week 12 to q8w or every 12 weeks (q12w); IAI to q8w, q12w, or HD combo q8w through Week 32.RESULTS: Week 12 best-corrected visual acuity gains for LD and HD combo versus IAI were 6.8, 8.5, and 8.8 letters; Week 36 changes were similar. Central subfield retinal thickness reductions at Week 12 were -169.4, -184.0, and -174.6 µm (nominal P = 0.0183, HD combo vs. IAI); Week 36 reductions for LD combo and HD combo q8w and q12w versus IAI were -210.4, -223.4, and -193.7 versus -61.9 µm (nominal P < 0.05). At Week 12, 13.3% and 21.3% versus 15.2% had ≥2-step Diabetic Retinopathy Severity Scale improvement (LD and HD combos vs. IAI) and 59.6% and 66.3% versus 53.7% had complete foveal center fluid resolution. Safety was comparable across groups.CONCLUSION: Nesvacumab + aflibercept demonstrated no additional visual benefit over IAI. Anatomic improvements with HD combo may warrant further investigation.
AB - PURPOSE: The purpose of this study was to compare intravitreal nesvacumab (anti-angiopoietin 2) plus aflibercept with intravitreal aflibercept injection (IAI) in diabetic macular edema.METHODS: The eyes (n = 302) were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, Weeks 4 and 8. LD combo continued every 8 weeks (q8w). HD combo was rerandomized at Week 12 to q8w or every 12 weeks (q12w); IAI to q8w, q12w, or HD combo q8w through Week 32.RESULTS: Week 12 best-corrected visual acuity gains for LD and HD combo versus IAI were 6.8, 8.5, and 8.8 letters; Week 36 changes were similar. Central subfield retinal thickness reductions at Week 12 were -169.4, -184.0, and -174.6 µm (nominal P = 0.0183, HD combo vs. IAI); Week 36 reductions for LD combo and HD combo q8w and q12w versus IAI were -210.4, -223.4, and -193.7 versus -61.9 µm (nominal P < 0.05). At Week 12, 13.3% and 21.3% versus 15.2% had ≥2-step Diabetic Retinopathy Severity Scale improvement (LD and HD combos vs. IAI) and 59.6% and 66.3% versus 53.7% had complete foveal center fluid resolution. Safety was comparable across groups.CONCLUSION: Nesvacumab + aflibercept demonstrated no additional visual benefit over IAI. Anatomic improvements with HD combo may warrant further investigation.
KW - diabetic macular edema
KW - investigational clinical trials
KW - prospective study
KW - randomized controlled trial
KW - vascular endothelial growth factor
KW - Receptors, Vascular Endothelial Growth Factor/therapeutic use
KW - Vascular Endothelial Growth Factor A
KW - Double-Blind Method
KW - Intravitreal Injections
KW - Humans
KW - Macular Edema/diagnosis
KW - Antibodies, Monoclonal/therapeutic use
KW - Diabetes Mellitus
KW - Visual Acuity
KW - Recombinant Fusion Proteins/therapeutic use
KW - Angiogenesis Inhibitors/therapeutic use
KW - Diabetic Retinopathy/complications
UR - http://www.scopus.com/inward/record.url?scp=85127477012&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85127477012&partnerID=8YFLogxK
U2 - 10.1097/IAE.0000000000003441
DO - 10.1097/IAE.0000000000003441
M3 - Article
C2 - 35234673
AN - SCOPUS:85127477012
SN - 0275-004X
VL - 42
SP - 1111
EP - 1120
JO - Retina
JF - Retina
IS - 6
ER -