Real-World Outcomes after 36-Month Treatment with Ranibizumab 0.5 mg in Patients with Visual Impairment due to Diabetic Macular Edema (BOREAL-DME)

Abstract

<b><i>Purpose:</i></b> To assess the efficacy, safety, and follow-up of 36-month treatment with ranibizumab in patients with diabetic macular edema (DME) in real-life setting. <b><i>Methods:</i></b> This is a prospective phase 4 observational study. Between December 2013 and April 2015, 84 ophthalmologists enrolled a total of 290 adult patients initiating ranibizumab for visual impairment due to DME and treated them according to their routine practice. The primary outcome (mean change in best-corrected visual acuity [BCVA] after 12 months) was previously reported. Here, we present outcomes after 36 months of follow-up for BCVA and change in central subfield thickness (CSFT) and report how participating ophthalmologists treated DME over a 3-year period (number of visits and injections and evolution of treatment strategy). <b><i>Results:</i></b> Of the 290 patients enrolled, 187 (64.5%) completed the 36 months of the study (entire cohort). In the entire cohort, 97 patients were treated exclusively with ranibizumab throughout the study, and 90 patients switched to other intravitreal treatments. Mean BCVA was 64.2 (20.1) letters, representing a gain of +4.1 (19.9) letters from baseline to month 36 (M36). CSFT improved over the study, and by M36 had decreased by 127 (138) µm compared to baseline. Over the 36 months of follow-up, patients in the entire cohort paid their ophthalmologists a mean of 30.9 (12.2) visits and had a mean of 7.6 (5.2) any injections. Results for quality of life questionnaires NEI-VFQ25 and HUI-3 remained stable throughout the study. Multivariate analysis on the 145 patients with evaluable BCVA data at M36 found that male gender and milder baseline DME characteristics (BCVA ≥59 and CSFT <500 µm) were predictive factors for achieving a BCVA of ≥70 letters at M36. This study did not find any new safety signals, compared to the known profile of ranibizumab. <b><i>Conclusions:</i></b> Gains in BCVA in this real-life study were lower than those observed in randomized clinical trials with ranibizumab, mainly due to undertreatment. Safety analysis of ranibizumab did not yield any new safety concerns.

ETOILE: Real-World Evidence of 24 Months of Ranibizumab 0.5 mg in Patients with Visual Impairment Due to Diabetic Macular Edema

“…Massin reported mean BCVA gains of +4.1 letters after 36 months. 15 However, in this cohort, only half of the patients who completed the 36-month follow-up had been treated with ranibizumab only, the remaining patients switched to other intravitreal drugs. The ETOILE cohort had similar baseline BCVA and gains at M24, and similar numbers of injections.…”

“…Under-treatment was also reported in another three-year French prospective real-world study of ranibizumab in DME that showed fewer visits (mean 13.4) and injections (mean 5.1) than recommended in year 1, decreasing further in subsequent two years. 15 …”

“…This rate was similar to previous real-world studies by Best et al (25.45% after one year of follow-up) 16 and Massin et al (35.5% after three years). 15 In ETOILE, 25.8% of patients had switched to other intravitreal therapy by M24. A similar rate of switching was observed after 4 years (25.4%) in a Danish retrospective cohort of 566 DME patients.…”

“…Conversion of results to ETDRS letters has been used in other studies of anti-VEGF in DME. 15 , 18 , 19 …”

“…Under-treatment was also reported in another three-year French prospective real-world study of ranibizumab in DME that showed fewer visits (mean 13.4) and injections (mean 5.1) than recommended in year 1, decreasing further in subsequent two years. 15 One third of patients in ETOILE were lost to follow-up by M24, for any reason. This rate was similar to previous real-world studies by Best et al (25.45% after one year of follow-up) 16 and Massin et al (35.5% after three years).…”