Henry E Wiley1, Darby J S Thompson2, Clare Bailey3, Emily Y Chew4, Catherine A Cukras4, Glenn J Jaffe5, Richard W J Lee6, Erin K Loken2, Catherine B Meyerle7, Wai Wong4, Frederick L Ferris4. 1. National Eye Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: wileyhe@nei.nih.gov. 2. The Emmes Corporation, Rockville, Maryland. 3. University Hospitals Bristol National Health Service Foundation Trust, Bristol, United Kingdom. 4. National Eye Institute, National Institutes of Health, Bethesda, Maryland. 5. Duke Reading Center, Durham, North Carolina. 6. University Hospitals Bristol National Health Service Foundation Trust, Bristol, United Kingdom; School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and University College London Institute of Ophthalmology, London, United Kingdom. 7. Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland.
Abstract
PURPOSE: To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. DESIGN: Randomized, double-masked, 36-week, 3-period crossover clinical trial. PARTICIPANTS: Fifty-six subjects with DME involving the center of the macula in one or both eyes. METHODS: Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). MAIN OUTCOME MEASURES: Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. RESULTS: Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 μm for bevacizumab and -137 μm for ranibizumab (difference, 48 μm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 μm (95% CI, -155 to -100) for bevacizumab and -176 μm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next. CONCLUSIONS: This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab, ranibizumab, and aflibercept for DME. The 3-period crossover design allowed for meaningful and efficient comparison, suggesting that this approach may be useful for future comparative efficacy studies of anti-vascular endothelial growth factor drugs for DME. Published by Elsevier Inc.
RCT Entities:
PURPOSE: To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. DESIGN: Randomized, double-masked, 36-week, 3-period crossover clinical trial. PARTICIPANTS: Fifty-six subjects with DME involving the center of the macula in one or both eyes. METHODS: Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). MAIN OUTCOME MEASURES: Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. RESULTS: Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 μm for bevacizumab and -137 μm for ranibizumab (difference, 48 μm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 μm (95% CI, -155 to -100) for bevacizumab and -176 μm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next. CONCLUSIONS: This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab, ranibizumab, and aflibercept for DME. The 3-period crossover design allowed for meaningful and efficient comparison, suggesting that this approach may be useful for future comparative efficacy studies of anti-vascular endothelial growth factor drugs for DME. Published by Elsevier Inc.
Authors: Mark C Gillies; Lyndell L Lim; Anna Campain; Godfrey J Quin; Wedad Salem; Ji Li; Stephanie Goodwin; Christine Aroney; Ian L McAllister; Samantha Fraser-Bell Journal: Ophthalmology Date: 2014-08-22 Impact factor: 12.079
Authors: Ingrid U Scott; Allison R Edwards; Roy W Beck; Neil M Bressler; Clement K Chan; Michael J Elman; Scott M Friedman; Craig Michael Greven; Raj K Maturi; Dante J Pieramici; Michel Shami; Lawrence J Singerman; Cynthia R Stockdale Journal: Ophthalmology Date: 2007-08-15 Impact factor: 12.079
Authors: M L Subramanian; G Abedi; S Ness; E Ahmed; M Fenberg; M K Daly; A Houranieh; E B Feinberg Journal: Eye (Lond) Date: 2010-10-01 Impact factor: 3.775
Authors: Usha Chakravarthy; Simon P Harding; Chris A Rogers; Susan M Downes; Andrew J Lotery; Sarah Wordsworth; Barnaby C Reeves Journal: Ophthalmology Date: 2012-05-11 Impact factor: 12.079
Authors: Kevin J Blinder; Pravin U Dugel; Sanford Chen; J Michael Jumper; John G Walt; David A Hollander; Lanita C Scott Journal: Clin Ophthalmol Date: 2017-02-21
Authors: Alex S Willoughby; Stephanie J Chiu; Rachel K Silverman; Sina Farsiu; Clare Bailey; Henry E Wiley; Frederick L Ferris; Glenn J Jaffe Journal: Transl Vis Sci Technol Date: 2017-02-07 Impact factor: 3.283
Authors: Maja Kostic; Nathan M Bates; Nebojsa T Milosevic; Jing Tian; William E Smiddy; Wen-Hsiang Lee; Gabor M Somfai; William J Feuer; Joyce C Shiffman; Ajay E Kuriyan; Ninel Z Gregori; Sandra Pineda; Delia Cabrera DeBuc Journal: Front Physiol Date: 2018-09-05 Impact factor: 4.566
Authors: Jennifer K Sun; Kristin Josic; Michele Melia; Adam R Glassman; Clare Bailey; Kakarla V Chalam; Emily Y Chew; Catherine Cukras; Sandeep Grover; Glenn J Jaffe; Richard Lee; Jared S Nielsen; Darby J S Thompson; Henry E Wiley; Frederick L Ferris Journal: Transl Vis Sci Technol Date: 2021-12-01 Impact factor: 3.283
Authors: Anika Tanwani; Nida Safdar; Amir Ali; Cina Karimaghaei; Mary Schmitz-Brown; Ahmad Rehmani; Praveena K Gupta Journal: Life (Basel) Date: 2021-12-31