Author: Atul Kumar (India)
Co-authors: Unnikrishnan Nair, Santosh Gopikrishnan, Padmaja Kumari Rani, Aditya Sudhalkar, Zahir Abbas, Utkarsh Shah
Diabetic macular edema (DME) is one of the most common retinal vascular disease, which is caused by diabetic retinopathy. The visual impairment in diabetic retinopathy is mainly due to macular edema, which arises from increased permeability of the inner blood-retina barrier resulting in the accumulation of fluid in the retina, leading to deterioration in detailed vision. Vascular endothelial growth factor (VEGF) plays an important role in the development of DME. Ranibizumab, a humanized anti-VEGF monoclonal antibody fragment, has exhibited halting the growth of choroidal neovascularization lesions, reduce vascular leakage, and effectively controlling the macular edema in patients with DME. Clinical trials till date have affirmed the efficacy of ranibizumab in patients with DME, due to which it is already authorized in India since 17 July 2014. Hence, current study was done as part of the regulatory requirement to collect real-world effectiveness, safety, and tolerability data of ranibizumab in the management of DME.
This was a non-interventional, prospective, observational, open-label study conducted across 10 centres in India for a period of 48 weeks. Participants included in the study were adult outpatients (men/women ≥18 years old) with decreased vision due to macular edema secondary to type 1/type 2 diabetes mellitus (DM); vision impairment due to DME; unsatisfactory outcomes from the prior DME treatment (Snellen Equivalent scores ranging from presence of perception of light [PL+] to 6/9 for the affected eye), and who were prescribed ranibizumab by their treating ophthalmologist in adherence with the local summary of product characteristics and prescribing information.
Overall 125 patients were treated with intravitreal injection of ranibizumab (Accentrix®) 0.5 mg (0.05 mL volume) at baseline and then after every 4 weeks, for a duration based on clinical judgement of the treating ophthalmologist substantiated by the changes seen in visual acuity and optical coherence tomography (OCT). Injection was repeated as per the visual stability criteria for three consecutive monthly visits. There was no reference therapy or comparator drug for the patients. Primary effectiveness endpoint was mean change from baseline in early treatment diabetic retinopathy study (ETDRS) letters in best-corrected visual acuity (BCVA) at 48 weeks. Secondary effectiveness endpoints included visit wise changes in the ETDRS letters in BCVA from the baseline; number (%) of patients gaining ≥15 EDTRS letters (or 3 ETDRS rows) at weeks 12, 24, and 48; change from baseline in the central retinal thickness (CRT) on OCT; progression of the avascular area since baseline assessed from the foveal avascular zone (FAZ) using fluorescein angiography; and change from baseline in the number (%) of patients with retinal hemorrhage determined by fundus photography. Safety was assessed through the adverse events (AEs), serious AEs (SAEs), and treatment-emergent AEs (TEAEs) reported during the study period.
Of the 125 patients, 68 (54.0%) patients completed the study. Mean (±standard deviation [SD]) age of the population was 59.6±8.28 years and ~65% were men. Each patient on an average received 3.5 intravitreal injections over 48 weeks. For primary effectiveness analysis, there was statistically significant improvement in ETDRS letters post 48-week treatment (change from baseline: 6.8±17.38, p=0.0019). A significant improvement (p≤0.0010) was seen in this parameter across all study visits. Number (%) of patients gaining ≥15 ETDRS letters (or 3 ETDRS rows) at weeks 12, 24, and 48 were 26 (28.6%), 16 (22.5%), and 19 (27.5%), respectively. A significant (p<0.0001) and consistent decrease in mean CRT was observed from baseline (433.1±146.66 µm) till week 48 (307.2±122.65 µm). No statistically significant change was observed in the progression of avascular area over the treatment period (p>0.05). Number (%) of patients with retinal hemorrhage decreased from 80 (64.0%) at baseline to 24 (34.8%) at 48 weeks. Majority of patients (110 [88%]) did not experience any AEs. Five patients (4.0%) reported six SAEs with no suspected relation to ranibizumab/ocular injection. Most frequent TEAEs were vitreous hemorrhage (2.4%) and conjunctivitis (1.6%).
This was the first real-world study conducted in the Indian population with DME. The ranibizumab 0.5 mg intravitreal injection was found to be effective in improving the visual acuity and the treatment was found to be well tolerated among the Indian patients with visual impairment due to DME. The overall findings were corresponding to the efficacy findings from the clinical trials and were consistent with the prescription details as well as the AEs reported in the summary of product characteristics of ranibizumab.
The prospective, open-label study was sponsored by Novartis Healthcare Private Limited (Mumbai, India).