Withdrawal from ranibizumab or panretinal laser photocoagulation (PRP) monotherapy can lead to an increase in the neovascularization area (NV) and loss of visual acuity in patients with proliferative diabetic retinopathy, according to research published in Acta Ophthalmologica.
The PRIDE study (ClinicalTrials.gov ID NCT01594281) was a randomized, open, controlled, multicenter phase 2 study, 12 months, 1: 1: 1 with an observation phase to compare ranibizumab vs. PRP vs. combination therapy in patients with proliferative diabetic retinopathy, but without diabetic macular edema. The PRIDE study took place between 2012 and 2017, and the current study presents the results of the second year of observation.
A total of 106 patients took part in the first intervention phase, from the start of the study to month 12. The participants were randomized to receive either ranibizumab 0.5 mg (n = 35), PRP (n = 35) or the combination ranibizumab 0.5 mg plus PRP (n = 36). Twenty-eight, 20 and 25 patients from each group participated in the follow-up from the 12th to the 24th month.
A total of 74 patients entered the follow-up phase, of which 67 completed the visits in month 24 (25, 19 and 23 in each group, respectively). Baseline characteristics were generally well balanced across groups, with the exception of the mean NV area, which was higher in the ranibizumab group compared to the PRP and combination groups (9.02 ± 14.63 mm2 vs 6.19 ± 12.29 mm2 and 2.71 ± 4.09 mm2). In addition, there were more active smokers in the combination group – 36% – compared to the ranibizumab and PRP groups (14.3% vs 10%).
Study medication was not administered during the entire observation period and patients were treated at the investigator’s discretion.
In the first year, treatment with ranibizumab as monotherapy was associated with a significantly greater reduction in the NV area from baseline up to month 12 compared to PRP; the comparisons between ranibizumab and combination therapy and combination therapy and PRP were not significant.
During the observation phase, the mean NV area in the ranibizumab group increased from 3.16 ± 4.30 mm2 to 6.09 ± 10.79 mm2 in months 12 and 18 and to 10.00 ± 17.63 mm2 in Month 24. In the PRP group there was a decrease in the NV area from 5.44 ± 14.55 mm2 to 1.22 ± 1.67 mm2 between the 12th and 18th month, then increased to 4.05 ± 11.66 mm2 in the 24th month.
In the combination group, the NV area increased from 1.13 ± 2.78 mm2 to 2.14 ± 4.41 mm2 to 3.26 mm2 in months 12, 18 and 24, respectively.
The mean LS change in the NV area from the start of the study to month 24 was 1.0 mm2 (95% CI, -3.2 to 5.1), -2.2 mm2 (95% CI, -6.9) up to 2.5) and -0.6 mm2 (95% CI, -5.2.). to 3.9) in each group. Differences between the groups were not significant.
The number of patients who developed new neovascularization (NVE) elsewhere from baseline in each group was 7, 5, and 6 at month 12, 10, 5, and 10 at month 18, and 10, 8, and 12 in, respectively Month 12.
In the ranibizumab group, 22.2%, 11.1%, and 12% of patients had complete regression of NV leakage at any point in time; in the PRP group these figures were 10%, 21.1% and 23.5% and in the combination group 20%, 16.7% and 22.7%, respectively.
The percent agreement for detection of NVE in fluorescein angiography was 94.6%, and detection of disc neovascularization (NVD) was 100% in terms of grading reproducibility. The median difference between the ratings for the SSCC area was 0.11 ± 1.21 mm2, with a median of the original rating of 0.52 ± 6.62 mm2. For the NVD area, the median difference was 0.00 ± 0.14 mm2 and the median value of the original classification was 0.00 ± 0.23 mm2.
During the first year of study, a significant difference in LS mean best-corrected visual acuity of 5.5 letters was observed between the ranibizumab and PRP groups. There was no significant difference between the ranibizumab and combination groups and between the PRP and combination groups.
During the observation period, the BCVA in the ranibizumab group decreased from 85.6 ± 7.6 letters in the 12th month to 81.9 ± 10.8 letters in the 18th month, before falling slightly to 82.4 ± 9.9 letters in the 24th month increased decreased between months 12 and 18 before increasing to 78.7 ± 16.8 letters after 24 months. In the patients in the combination group, BCVA increased from 81.4 ± 9.3 letters to 82.5 ± 6.9 letters and decreased to 78.5 ± 18.3 between the 12th and 18th month Letters in the 24th month.
The mean LS change in BCVA in each group was -1.1 letters, -2.0 letters and -4.2 letters, respectively. Differences between the groups were not significant.
During the first year, significant LS mean differences in CST change were observed in the ranibizumab and PRP groups and between the ranibizumab and combination groups; the difference between the PRP group and the combination group was not significant.
During the observation period, the mean CST in the ranibizumab group increased from month 12 to 18 and from month 18 to 24. In the PRP group the mean CST decreased at each point in time and in the combination group the mean CST was relatively constant in months 12 and 18 – 254.5 ± 37.1 µm and 254.9 ± 29.2 µm – before they increase to 265.6 ± 33.4 µm after 24 months.
At months 12, 0, 7 and 2 patients with macular edema in each group. During the observation period, 1, 5, and 2 patients developed macular edema at month 18, and 3, 5, and 3 patients had macular edema at month 24.
No antiplatelet cooperation events were recorded for any treatment group during the follow-up period. Vitrectomy was not performed in any patient in the ranibizumab or PRP group, while vitrectomy was required in 2 patients in the combination group. For severe ocular side effects, 1, 2, and 4 patients in each group had these results.
One of the limitations of the study is the relatively small number of patients in each follow-up group, which limits the generalizability of the results.
“[O]Our data from the 12-month follow-up of the PRIDE study in the second year show that [patients with proliferative diabetic retinopathy] require regular monitoring of disease activity, ”the researchers say. “Continuous treatment is important for patients receiving anti-VEGF therapy to ensure that the benefits are not lost with recurrent NV activity.”
Lang GE, Stahl A, Voegeler J, et al. Observation results in patients with proliferative diabetic retinopathy after treatment with ranibizumab, panretinal laser photocoagulation, or combination therapy – The non-interventional follow-up of the PRIDE study in the second year. Acta Ophthalmol. Published online June 14, 2021. doi: 10.1111 / aos.14907
This article originally appeared on Ophthalmology Advisor