More patients in the RIDE and RISE trials treated with the VEGF inhibitor showed improvements in vision test scores compared to patients who received placebo.
More patients in the RIDE and RISE trials treated with the VEGF inhibitor ranibizumab showed improvements in vision test scores compared to patients who received placebo.
In a presentation of late-breaking clinical studies at the ADA 71st Scientific Sessions in San Diego, David S. Boyer, MD, of Retina-Vitreous Associates Medical Group in Los Angeles, CA, described results from two trials of ranibizumab for vision loss due to diabetic macular edema. The RIDE and RISE studies were identical 24-month phase III trials that demonstrated superior effects compared to placebo of ranibizumab on rapid and sustained vision improvement, reduced progression of diabetic retinopathy, patient-reported visual function, and ocular and systemic safety consistent with other ranibizumab studies.
The American Academy of Ophthalmology recommends that patients with type 1 diabetes be examined by an ophthalmology professional three years after initial diagnosis, and recommends that patients with type 2 diabetes should be seen at the time of diagnosis. However, “40-50% of patients do not receive recommended eye care, often because they don’t experience pain,” said Boyer. Diabetic retinopathy (DR) is the most common microvascular complication associated with diabetes, occurring in 28.5% of diabetics age 40 and older. Diabetic macular edema (DME) is swelling of the retina which occurs frequently in patients with DR and in approximately 10% of diabetics. DME can cause blindness, severe vision loss, or blurred or distorted vision.
Standard treatment for DME is laser photocoagulation, but it rarely leads to vision improvement. When it does, the vision gain is small and takes a long time. Ranibizumab is an anti-VEGF (vascular endothelial growth factor A) antibody fragment designed for intraocular use. The objective of the RIDE and RISE trials was to evaluate the safety and efficacy of intravitreal injections of ranibizumab compared to placebo in patients with DME. Patients were randomized to 0.3 or 0.5 mg ranibizumab or sham injections. Primary endpoint was the proportion of patients who gained three or more lines from baseline on a standardized eye chart. Secondary endpoints were various measures of visual acuity and visual function.
Results revealed vision improvements as early as week 1, with statistically significant improvements in both the 0.3 and 0.5 mg groups compared to sham injections. The percent of patients able to read at least three lines compared to baseline was 18.1 and 12.3 for the sham injections (RISE and RIDE, respectively), 44.8 and 33.6 for 0.3 mg ranibizumab, and 39.2 and 45.7 for 0.5 mg ranibizumab. The percent of patients who progressed to proliferative DR was much lower in the treatment groups than the sham groups (1.6 to 5.6 and 11.5 to 15.0, respectively). Boyer highlighted one slide in particular that showed results for patients with 20/40 vision, which is often necessary for people to maintain their driver’s licenses. In the sham group, there was not much improvement, with 34.6% and 37.8% of patients with 20/40 vision. This was almost doubled in the treatment groups (54.4% to 63.2%). Results were similar whether A1C was under good control or bad control.
“Sometimes we measure things and say they’re statistically significant,” explained Boyer, “but are they clinically significant?” The National Eye Institute of Visual Function Questionnaire (NEI VFQ-25) was used to measure patients’ perception of treatment impact. Patients in the treatment groups reported greater improvements in vision-related activities such as reading and hobbies compared to those in the sham groups. Safety appeared to be consistent with what we had in all other trials with raniziumab.
Boyer concluded by saying that safety and efficacy results from both studies show a “potential new standard of treatment for patients with DME, as well as underscore the need for retinal examination in patients with diabetes.”