Jeffrey S Heier1, Jean-François Korobelnik2, David M Brown3, Ursula Schmidt-Erfurth4, Diana V Do5, Edoardo Midena6, David S Boyer7, Hiroko Terasaki8, Peter K Kaiser9, Dennis M Marcus10, Quan D Nguyen5, Glenn J Jaffe11, Jason S Slakter12, Christian Simader4, Yuhwen Soo13, Thomas Schmelter14, Robert Vitti13, Alyson J Berliner13, Oliver Zeitz15, Carola Metzig14, Frank G Holz16. 1. Ophthalmic Consultants of Boston, Boston, Massachusetts. 2. Service d'ophtalmologie, CHU de Bordeaux, France; University Bordeaux, ISPED, F-33000 Bordeaux, Bordeaux, France; Inserm, U1219 - Bordeaux Population Health Research Center, F-33000 Bordeaux, France. 3. Retina Consultants of Houston, Houston, Texas. 4. Medical University of Vienna, Vienna, Austria. 5. Ocular Imaging Research and Reading Center, Omaha, Nebraska. 6. Department of Ophthalmology, University of Padova, Padova, Italy. 7. Retina-Vitreous Associates Medical Group, Beverly Hills, California. 8. Nagoya University Hospital, Nagoya, Japan. 9. Cole Eye Institute, Cleveland, Ohio. 10. Southeast Retina Center, Augusta, Georgia. 11. Department of Ophthalmology, Duke University, Durham, North Carolina. 12. Vitreous-Retina-Macula Consultants of New York, New York, New York. 13. Regeneron Pharmaceuticals, Inc, Tarrytown, New York. 14. Bayer HealthCare, Berlin, Germany. 15. Bayer HealthCare, Berlin, Germany; University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 16. Department of Ophthalmology, University of Bonn, Bonn, Germany. Electronic address: Frank.Holz@ukb.uni-bonn.de.
Abstract
PURPOSE: To compare efficacy and safety of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for diabetic macular edema (DME) over 3 years. DESIGN: Two similarly designed phase 3 trials: VISTADME and VIVIDDME. PARTICIPANTS: Patients (eyes; n = 872) with central-involved DME. METHODS: Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or laser control. From week 24, if rescue treatment criteria were met, IAI patients received active laser, and laser control patients received IAI 2q8. From week 100, laser control patients who had not received IAI rescue treatment received IAI as needed per retreatment criteria. MAIN OUTCOME MEASURES: The primary end point was the change from baseline in best-corrected visual acuity (BCVA) at week 52. We report the 148-week results. RESULTS:Mean BCVA gain from baseline to week 148 with IAI 2q4, IAI 2q8, and laser control was 10.4, 10.5, and 1.4 letters (P < 0.0001) in VISTA and 10.3, 11.7, and 1.6 letters (P < 0.0001) in VIVID, respectively. The proportion of eyes that gained ≥15 letters from baseline at week 148 was 42.9%, 35.8%, and 13.6% (P < 0.0001) in VISTA and 41.2%, 42.2%, and 18.9% (P < 0.0001) in VIVID, respectively. Greater proportions of eyes treated with IAI 2q4 and IAI 2q8 versus those treated with laser control had an improvement of ≥2 steps in the Diabetic Retinopathy Severity Scale (DRSS) score in both VISTA (29.9% and 34.4% vs. 20.1% [P = 0.0350, IAI 2q4; P = 0.0052, IAI 2q8]) and VIVID (44.3% and 47.8% vs. 17.4% [P < 0.0001 for both]). In an integrated safety analysis, the most frequent ocular serious adverse event was cataract (3.1%, 2.1%, 0.3% for 2q4, 2q8, and control). CONCLUSIONS: Visual improvements observed with both IAI regimens (over laser control) at weeks 52 and 100 were maintained at week 148, with similar overall efficacy in the IAI 2q4 and IAI 2q8 groups. Treatment with IAI also had positive effects on the DRSS score. Over 148 weeks, the incidence of adverse events was consistent with the known safety profile of IAI.
RCT Entities:
PURPOSE: To compare efficacy and safety of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for diabetic macular edema (DME) over 3 years. DESIGN: Two similarly designed phase 3 trials: VISTADME and VIVIDDME. PARTICIPANTS: Patients (eyes; n = 872) with central-involved DME. METHODS: Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or laser control. From week 24, if rescue treatment criteria were met, IAI patients received active laser, and laser control patients received IAI 2q8. From week 100, laser control patients who had not received IAI rescue treatment received IAI as needed per retreatment criteria. MAIN OUTCOME MEASURES: The primary end point was the change from baseline in best-corrected visual acuity (BCVA) at week 52. We report the 148-week results. RESULTS: Mean BCVA gain from baseline to week 148 with IAI 2q4, IAI 2q8, and laser control was 10.4, 10.5, and 1.4 letters (P < 0.0001) in VISTA and 10.3, 11.7, and 1.6 letters (P < 0.0001) in VIVID, respectively. The proportion of eyes that gained ≥15 letters from baseline at week 148 was 42.9%, 35.8%, and 13.6% (P < 0.0001) in VISTA and 41.2%, 42.2%, and 18.9% (P < 0.0001) in VIVID, respectively. Greater proportions of eyes treated with IAI 2q4 and IAI 2q8 versus those treated with laser control had an improvement of ≥2 steps in the Diabetic Retinopathy Severity Scale (DRSS) score in both VISTA (29.9% and 34.4% vs. 20.1% [P = 0.0350, IAI 2q4; P = 0.0052, IAI 2q8]) and VIVID (44.3% and 47.8% vs. 17.4% [P < 0.0001 for both]). In an integrated safety analysis, the most frequent ocular serious adverse event was cataract (3.1%, 2.1%, 0.3% for 2q4, 2q8, and control). CONCLUSIONS: Visual improvements observed with both IAI regimens (over laser control) at weeks 52 and 100 were maintained at week 148, with similar overall efficacy in the IAI 2q4 and IAI 2q8 groups. Treatment with IAI also had positive effects on the DRSS score. Over 148 weeks, the incidence of adverse events was consistent with the known safety profile of IAI.
Authors: Justis P Ehlers; Atsuro Uchida; Ming Hu; Natalia Figueiredo; Peter K Kaiser; Jeffrey S Heier; David M Brown; David S Boyer; Diana V Do; Andrea Gibson; Namrata Saroj; Sunil K Srivastava Journal: Ophthalmol Retina Date: 2019-07-06
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