Real-World Outcomes in Patients with Diabetic Macular Edema Treated Long Term with Ranibizumab (VISION Study)

Elisabeth Van Aken,1,2 Mérédis Favreau,3 Eva Ramboer,3 Kris Denhaerynck,4,5 Karen MacDonald,4 Ivo Abraham,4,6– 8 Heidi Brié3 1Department of Ophthalmology, AZ Sint-Elisabeth, Zottegem, Belgium; 2Department of Head and Skin, Ghent University, Ghent, Belgium; 3Medical Department, Novartis Pharma, Vilvoorde, Belgium; 4Department of Research and Consulting, Matrix45, Tucson, AZ, USA; 5Department of Public Health, University of Basel, Basel, Switzerland; 6Center for Health Outcomes and Pharmacoeconomic Research, University of Arizona, Tucson, AZ, USA; 7Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ, USA; 8Department of Family and Community Medicine, College of Medicine – Tucson, University of Arizona, Tucson, AZ, USACorrespondence: Heidi BriéN.V. Novartis Pharma S.A, Medialaan 40, B-1800 Vilvoorde, BelgiumTel +32.2.246.1774Email heidi.brie@novartis.comAim: Evaluate long-term real-world treatment patterns and associated effectiveness and safety outcomes in patients with diabetic macular edema (DME) treated ≥ 36 months with 0.5mg ranibizumab.Methods: Open-label observational effectiveness study in 9 Belgian clinics. Included were primary treated eyes of 55 DME patients between August 2014 and March 2015 and followed for 3.5± 1.8 years. Eyes were 21.8% treatment (TX)-naïve, 9.1% non-naïve with exclusive prior anti-VEGF treatment (PRIOR-anti-VEGF), and 63.6% non-naïve with other prior treatments (PRIOR-other). Intravitreal injections with ranibizumab were administered per ophthalmologists’ best clinical judgment. Trend testing of changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) over time occurred using mixed regression analysis.Results: The mean±SD number of treatments in the first year was 5.1± 3.0 (TX-naïve), 4.5± 2.7 (PRIOR-anti-VEGF) and 5.6± 3.1 (PRIOR-other). At 12 months, BCVA increased by 8.9± 16.4 letters from 59.7± 9.3 at baseline in TX-naïve (p< 0.0001), by 11.8± 9.9 from 61.6± 8.5 in PRIOR-anti-VEGF (p=0.03), and by 4.2± 10.6 from 58.2± 14.6 in PRIOR-other groups (p=0.0002). BCVA remained stable for the remainder of follow-up in all groups. CRT decreased over the first 2 months by monthly rates of − 43.8μm in TX-naïve (p=0.04), − 75.7μm in PRIOR-anti-VEGF (p=0.02), and − 65.8μm in PRIOR-other eyes (p=0.0003), showing stability afterwards. No unknown adverse events were recorded; a painful eye following injection was registered with a possible relationship to the treatment.Conclusion: This real-world study confirms the effectiveness of ranibizumab in preventing a decline in BCVA and demonstrated initial improvement and subsequent retention of BCVA in DME patients ≥ 36 months. Ranibizumab initially reduced and then maintained CRT. However, these data reveal that treatment intensity and BCVA and CRT outcomes are lower than those found in early efficacy trials. Under-treatment likely accounts for this efficacy-effectiveness gap. Yet, intravitreal ranibizumab is an effective and safe long-term treatment for DME under conditions of significant heterogeneity in patients and treatment patterns.Keywords: diabetic macular edema, ranibizumab, best-corrected visual acuity, central retinal thickness, long-term effectiveness