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A 1-year extension of a two-year phase II study of treatment of diabetic macular edema allowed ranibizumab dosing frequency to increase from every 2 or 3 months to monthly.
Results from patients reaching the 36-month visit in the phase II, multicenter Ranibizumab for Edema of the mAcula in Diabetes (READ-2) show functional and anatomic improvements achieved earlier can be maintained or even increased with ongoing p.r.n. injections of intravitreal ranibizumab, but suggest that a more frequent injection regimen may optimize the benefit for some patients, said Thomas G. Chu, MD, PhD, at the annual meeting of the American Society of Retina Specialists.
READ-2 was originally designed as a 24-month study and randomly assigned 126 treatment-naïve patients at 14 centers into three groups (1:1:1) to receive ranibizumab 0.5 mg alone (group 1), focal/grid laser alone (group 2), or a combination of laser and ranibizumab (group 3). Initially, treatments were administered on a fixed schedule-patients in group 1 received ranibizumab at baseline and months 1, 3, and 5, and patients in groups 2 and 3 received their assigned treatments at baseline and month 3.
The primary efficacy assessment was conducted at month 6, and then through month 24, a p.r.n. dosing scheme of ranibizumab was initiated for all groups. Follow-up visits to assess DME recurrence were every 2 months for groups 1 and 2 and every 3 months for group 3. Ranibizumab was administered if central foveal thickness (CFT) on optical coherence tomography was ≥250 µm.
Based on a protocol amendment, patients who reached the 24-month visit could continue in the study for another year, but follow-up visit frequency and consequently the opportunity for re-treatment of recurrent edema was increased to monthly for all patients. Laser re-treatment could also be administered every 3 months in groups 2 and 3. While about 80% of patients in all three groups reached the month 24 visit, the proportion of eligible patients who continued past month 24 was 91% for group 1, 71% for group 2, and 74% for group 3. Considering patients eligible for the extension, only 85%, 65%, and 71% of those in groups 1, 2, and 3, respectively, reached the month 36 endpoint.
During the third year of the study, the average number of injections administered was 5.4 in group 1, 3.2 in group 2, and 2.3 in group 3. Patients in group 2 received a mean of 2 laser treatments and the mean number of laser treatments received by patients in group 3 was 1.
Analysis of data from the month 36 visit showed that compared with month 24, patients in groups 1 and 3 benefited with further improvement in ETDRS best-corrected visual acuity (BCVA) with mean gains from baseline of +10.3 letters and +9.5 letters, respectively. In group 2, mean BCVA decreased during the last year of the study with a final improvement of +1.4 letters from baseline.
"The 36-month outcomes need to be interpreted cautiously considering a notable drop-off in study participation, especially in the original laser-only group, resulting in small numbers of patients in each group," said Dr. Chu, a retinal specialist in private practice in Los Angeles. "Overall, however, the data are consistent with other emerging evidence suggesting a role for ranibizumab in the treatment of DME.
"In addition, the results show that the benefit of anti-vascular endothelial growth factor (VEGF) therapy can be maintained or even continue to improve during 3 years of treatment, but suggest that aggressive follow-up and re-treatment may be helpful in some patients," he said.
Patients were eligible for enrollment in READ-2 if their foveal thickness was at least 250 µm and Snellen equivalent BCVA was between 20/40 and 20/320. At enrollment, the demographic and baseline characteristics were similar in the three study groups. Mean Snellen equivalent BCVA was about 20/80, and across the three groups, mean foveal ranged from about 200 to about 250 µm.