Author: Ramachandran Unnikrishnan Nair (India)
Co-authors: Atul Kumar, Anubhav Goyal, Perwez Khan, Mohammad Arif Mulla, Aditya Kelkar, Nitin Maksane
Recent Indian survey reported a 16.9% prevalence of diabetic retinopathy among the individuals with diabetes mellitus (DM). Diabetic macular edema (DME) is evidently the most common cause of moderate vision loss in patients with diabetic retinopathy. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of DME, therefore anti-VEGF therapy is considered as current standard of care. Based on clinical trial outcomes, an anti-VEGF monoclonal antibody fragment, ranibizumab, has already been authorized in India since 17 July 2014 for the management of DME. Moreover, as part of the Indian regulatory requirement, a 48-week real-world study was conducted to evaluate effectiveness, safety, and tolerability of ranibizumab in patients with DME. Corresponding with the clinical trial findings, the real-world study demonstrated improved visual acuity with ranibizumab 0.5 mg intravitreal injection, which also was generally well tolerated in these patients. Evidence suggests that several factors—age of the patients, their HbA1c levels, smoking status to list a few—can influence the anti-VEGF treatment outcomes. Thus, the above-stated real-world study further analysed the treatment outcomes of ranibizumab in various subgroups of the study population. The present abstract focuses on the trends observed in various subgroups.
This 48-week, non-interventional, prospective, observational, open-label study was conducted at 10 centres across India between 29 July 2015 and 31 December 2017. Adult outpatients (≥18 years old) of either gender were included if they fulfilled the following criteria: decreased vision due to macular edema secondary to type 1/type 2 DM, vision impairment due to DME, unsatisfactory outcomes from 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 + every 4 weeks, for a duration as per clinical judgement of the treating ophthalmologist substantiated by the changes seen in visual acuity and optical coherence tomography (OCT). The study evaluated treatment effectiveness based on change from baseline in the following outcomes: early treatment diabetic retinopathy study (ETDRS) letters in best-corrected visual acuity (BCVA) at 48 weeks, visit-wise changes in this parameter, patients gaining ≥15 EDTRS letters/3 ETDRS rows with treatment; central retinal thickness (CRT) determined by OCT; progression of avascular area since baseline; and number of patients with retinal hemorrhage. The sub-group analysis was restricted to observing any trends for the mean change from baseline in the ETDRS letters in BCVA as well as in the CRT determined by OCT at 48 weeks. Pre-defined subgroups were patients’ age (18-64/65-74/75-84/>85 years), gender (men/women), smoking status (smokers/non-smokers), history of DM (type/duration), treatment of DM (oral hypoglycaemic agents [OHAs]/insulin/both), control of DM (based on HbA1c levels or blood sugar [BS] levels such as fasting [FBS]/post-prandial [PPBS]/random [RBS]/general random [GRBS]), and previous treatment for DME (not treated/laser treatment/photodynamic therapy/previous intraocular steroids/prior anti-VEGF therapy).
Overall 68 (54.0%) patients completed the study. Mean (±standard error [SE]) age of population was 59.6±0.74 years, majority were men (64.8%). Each patient on average received 3.5 intravitreal injections over 48 weeks. In overall population, there was statistically significant improvement in ETDRS letters in BCVA (change from baseline: 6.8±2.09, p=0.0019) post 48-week treatment. In the subgroup analysis for the given outcome, there was significant mean±SE change from baseline in ETDRS in BCVA observed in men (8.5±2.84, p=0.0045), non-smokers (7.2±2.17, p=0.0015), patients aged 18-64 years (6.6±2.31, p=0.0065), with type 2 DM (6.6±2.12, p=0.0026), and who did not receive any previous treatment for DME (7.4±2.62, p=0.0071). Based on OCT assessment in overall population, there was significant decrease in mean±SE CRT over 48 weeks (change from baseline: -89.7±19.02 µm, <0.0001). For the subgroup analysis, change in CRT from baseline was significant in men (-89.7±28.92 µm, p=0.0040) and women (-89.7±22.22 µm, p=0.0005) aged 18-64 years (-105±19.69 µm, p<0.0001), non-smokers (-92.8±19.56 µm, p<0.0001), patients with type 2 DM (-87.4±19.22 µm, p<0.0001), which was controlled by FBS (-81.7±32.83 µm, p=0.0235) or PPBS (-111±33.54 µm, p=0.0050), patients using OHAs (-209±72.41 µm, p=0.0449), and those who did not receive any treatment for DME (-92.6±24.66 µm, p=0.0006).
The subgroup analysis of this real-world study concluded that with the ranibizumab 0.5 mg intravitreal injection, there was a significant improvement in visual acuity among patients aged 18-64 years, men, non-smokers, patients with type 2 DM, and who did not receive any prior treatment for DME compared with other subgroups.
The prospective, open-label study was sponsored by Novartis Healthcare Private Limited (Mumbai, India).