Session Title: FP-15 Vascular Diseases and Diabetic Retinopathy V
Session Date/Time: Sunday 14/09/2014 | 08:00-10:00
Paper Time: 08:24
Venue: Boulevard D
First Author: : M.Larsen DENMARK
Co Author(s): : F. Boscia H. Gerding J. Mones I. Pearce S. Priglinger R. Tadayoni
Ranibizumab 0.5mg is approved for the treatment of macular edema secondary to retinal vein occlusion(RVO) in several countries worldwide based on the data from two phase III randomized double-masked 12-month controlled studies: BRAVO(branch RVO, BRVO) and CRUISE(central RVO, CRVO). BRIGHTER (NCT01599650) is designed to compare an individualized, stabilization-criteria driven pro re nata (PRN) regimen of ranibizumab 0.5mg, alone or combined with laser, versus laser alone up to Month 6 and then to evaluate its long-term(24 month) efficacy and safety in patients with visual impairment due to macular edema secondary to BRVO. We present the 6 month results from this study.
BRIGHTER is an ongoing 24 months phase IIIb open-label randomized active-controlled three-arm multicenter study that enrolled 455 BRVO patients with visual impairment due to macular edema from 81 sites in Europe, Australia and Canada.
A total of 455 patients were randomized 2:2:1 to ranibizumab alone (RBZ, n=183), ranibizumab + laser (RBZ+LSR, n=180) or laser alone (LSR, n=92). Patients in the RBZ and RBZ+LSR arms received monthly ranibizumab 0.5 mg until visual acuity (VA) stabilization and stability-criteria-driven PRN thereafter. Laser was applied on a PRN basis based on investigators’ assessment) to patients with perfused macular edema in the RBZ+LSR and LSR arms. After Month 6, LSR patients could be treated with ranibizumab. All patients will be monitored monthly up to Month 12 and then less frequently (up to 2-month intervals) depending on stable visual acuity and absence of disease activity. The key objectives were: superiority of RBZ or RBZ+LSR vs LSR at M6 (primary endpoint); non-inferiority of RBZ+LASER vs RBZ alone (to M24) and, if successful, to evaluate the impact of laser in reducing the number of RBZ retreatments up to Month 23. Exploratory objectives include the influence of baseline BCVA and duration of disease on treatment outcomes as well as differences in treatment response between ischemic and non-ischemic patients. Ischaemia was defined as present if capillary loss was detected by the Central Reading Center in any location of the center, inner or outer subfields.
424 patients (93.2%) completed 6 months of study. Baseline patient characteristics were generally balanced amongst the groups (RBZ/RBZ+LSR/LSR): mean age(years): 64.7/67.3/67.8; % female: 49.2/46.7/59.8; mean baseline VA (bVA, letters): 59.5/56.6/56.5. Compared to other studies there was a relatively larger proportion of patients with higher bVA: % of patients with bVA ≤39; 40-59; ≥60 letters were 8.7; 30.1; 60.1 (RBZ)/ 12.2; 40.0; 47.2 (RBZ+LSR) and 12; 39.1; 47.8 (LSR). Retinal ischemia was present in 87/71/41 patients. Mean(median) duration of BRVO (months) were 10.3(3.1)/9.3(3.3)/10.5(2.0). The primary endpoint was met, as RBZ alone or combined with laser was superior to laser alone in significantly improving mean BCVA from baseline to Month 6: +10.0 and +8.3 letters better than Laser (LSmeans, both p<0.0001), with an average of 4.8(RBZ) and 4.5(RBZ+LSR) RBZ injections. The mean BCVA gains (letters) in patients that were ischemic / non-ischemic at baseline were: 14.3/11.9 (RBZ); 14.4/11.8 (RBZ+LSR); 9.2/2.7 (LSR). Gains by baseline VA subgroups (≤39/40-59/≥60) were : 20.9/19.5/11.6 (RBZ); 19.5/16.8/11.1 (RBZ+LSR); 18.7/11.4/-1.4 (LSR). Gains by prior duration of BRVO (≤12/>12 months) were: 16.4/8.4 (RBZ); 15.0/11.5 (RBZ+LSR); 5.9/7.1 (LSR). There were no safety signals identified during the 6-months of the study, in particular no cases of endophthalmitis were reported.
The 6-month data from BRIGHTER demonstrated that PRN RBZ 0.5 mg alone or combined with laser is superior to laser alone in significantly improving VA in patients with BRVO. The exploratory analysis showed that RBZ, with or without laser, led to similar VA gains in both ischemic and non-ischemic patients. However, the benefits of laser monotherapy were almost negligible in non-ischemic and limited in ischemic patients. As expected, patients with poorer baseline VA had better improvement at month 6 than those with higher baseline VA. With regards to the impact of duration of BRVO on treatment response, the data showed that patients with shorter duration of disease (≤12 months) benefited more from RBZ than those with longer duration of BRVO (>12 months). This subgroup analysis supports that early initiation of RBZ treatment may provide prompt and substantial VA gains in BRVO patients. The 24 month data will contribute to understanding the long term efficacy and safety of RBZ in this disease. Overall the 6-month results from BRIGHTER study were comparable to the pivotal BRAVO study, in spite of differences in baseline VA, study population, and duration of BRVO.