Session Title: Vascular Diseases and Diabetic Retinopathy IV
Session Date/Time: Sunday 20/09/2015 | 09:00-10:30
Paper Time: 09:00
First Author: : R.Tadayoni FRANCE
Co Author(s): :
BRIGHTER (NCT01599650) was designed to compare an individualized stabilization criteria-driven pro re nata (PRN) dosing regimen of ranibizumab 0.5 mg (as approved in the European Union) with/without laser versus laser alone up to Month 6 and to further evaluate the long-term (24 months) efficacy and safety profile of ranibizumab in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). Here, we present the 24-month efficacy and safety outcomes for the BRIGHTER study.
BRIGHTER was a 24-month, phase IIIb, open-label, randomized, active-controlled, three-arm, multi-centre study that enrolled 455 patients with BRVO across 81 sites in Europe, Australia and Canada. METHODs: Patients with BRVO were randomized 2:2:1 to receive ranibizumab 0.5 mg (n=183), ranibizumab 0.5 mg with laser (n=180), or laser monotherapy, with an option for ranibizumab treatment to be added from Month 6 (n=92). Patients in the ranibizumab with/without laser groups received monthly ranibizumab until visual acuity (VA) was stable for 3 consecutive monthly assessments and stabilization criteria-driven PRN treatment thereafter. Laser was administered PRN based on the investigator’s assessment of patients with perfused macular edema in the ranibizumab with laser and laser monotherapy groups. Key objectives were to demonstrate the superiority of ranibizumab with/without laser versus laser alone based on mean best-corrected VA (BCVA) change from baseline to Month 24; to evaluate mean change in central subfield thickness [CSFT; assessed by the Vienna Central Reading Centre (CRC)] from baseline to Month 24 and to assess the safety profile over 24 months. Exploratory objectives were to evaluate the influence of baseline BCVA, disease duration and ischemia on BCVA outcomes. Retinal ischemia (assessed by the CRC) was defined as capillary loss (mild, moderate, severe or completely destroyed) in at least one location of the centre, inner or outer subfields, based on the Early Treatment Diabetic Retinopathy Study grid.
Overall, 380 (83.5%) patients completed the 24-month study. At baseline, ranibizumab, ranibizumab with laser, and laser monotherapy with/without ranibizumab from month 6 groups, had a mean VA of 59.5, 56.6 and 56.8/56.8 letters and mean (median) disease duration of 10.3 (3.1), 9.2 (3.3) and 10.5 (2.0)/2.2 (1.1) months, respectively, and 48.3%, 39.9%, 53.0%/25.0% of patients, respectively, had retinal ischemia. Ranibizumab and ranibizumab with laser was superior to laser monotherapy with/without ranibizumab from month 6 in improving mean BCVA from baseline to Month 24 (15.5 and 17.3 vs 12.1/10.0 letters; P<0.0001), with a mean of 11.4(ranibizumab), 11.3(ranibizumab with laser) and 8.1(laser monotherapy with ranibizumab from month 6) ranibizumab injections. Increased BCVA values were accompanied by reduction in mean CSFT at Month 24 (-224.7 and -248.9 vs -229.9/-107.5µm; P<0.0001). 24-month mean BCVA letter gain by baseline VA subgroups (≤39/40–59/≥60 letters) were 23.2/20.1/12.1 (ranibizumab), 22.7/22.2/11.8 (ranibizumab with laser) and 25.7/17.8/3.3 (laser); by prior BRVO duration (<3/≥12 months) were 17.7/8.4 (ranibizumab), 21.3/13.8 (ranibizumab with laser) and 11.0/12.4 (laser); and by ischemia (present/absent) were 15.4/12.9 (ranibizumab), 15.9/14.5 (ranibizumab with laser) and 15.9/5.2 (laser monotherapy with ranibizumab from month 6). The 24-month safety profile was consistent with the already established safety profile of ranibizumab.
The 24-month data from BRIGHTER demonstrated that individualized ranibizumab treatment with or without laser is superior to laser monotherapy in significantly improving BCVA in patients with BRVO. The exploratory analysis showed that patients with poor baseline VA had a better BCVA gain at Month 24 than those with higher baseline VA; however the absolute BCVA at Month 24 was better in patients with higher baseline VA. Likewise, patients with shorter duration of disease (<3 months) had higher BCVA gains, which suggests that earlier intervention with ranibizumab provides prompt and substantial VA gains. BRIGHTER included a large number of patients with ischemia, and ranibizumab treatment provided similar BCVA gains in both ischemic and non-ischemic groups treated with ranibizumab from study entry over 24 months. The 24-month data demonstrates the long-term efficacy and safety profile of ranibizumab in BRVO.