Efficacy and Cost-Effectiveness of Anti-VEGF for Treating Diabetic Retinopathy in the Indian Population

Figures & data

Table 1 Baseline Demographic and Disease Characteristics

Variables		RBZ + Laser N=77	BVZ +Laser N=51	p-value
Age [years (Mean ± SD)]		55.2±9.20	56 0.3±8.15	0.489
Gender	Male	42 (54.54%)	26 (50.98%)	0.692
	Female	35 (45.45%)	25 (49.01%)
Duration of DM [years (Mean ± SD)]		11.92±4.31	13.02±5.06	0.191
HbA1c (%)		7.56±3.2	7.42 ±4.1	0.829
Diabetic retinopathy type	Moderate NPDR + focal DME	40 (51.94%)	25 (49.01%)	0.801
	Severe NPDR+ diffused DME	24 (31.16%)	15 (29.41%)
	PDR+ diffused DME	13 (16.88%)	11 (21.56%)

Notes: Data were presented as mean ± SD. Normally distributed variables of two groups were compared by unpaired Student’s t-test. Not-normally distributed variables of the two groups were compared by the Mann–Whitney U-test. Categorical variables in two groups were presented as percentages (%) and compared by the Chi-Square test. The study showed no statistically significant difference in baseline demographic parameters. A value of p < 0.05 was considered statistically significant.

Abbreviations: RBZ, ranibizumab; BVZ, bevacizumab; DM, diabetes mellitus; HbA1c, glycated hemoglobin; NPDR, nonproliferative diabetic retinopathy; DME, diabetic macular edema; BCVA, best-corrected visual acuity; CMT, central macular thickness; IOP, intraocular pressure; SD, standard deviation.

Table 2 Improvement in “Best Corrected Visual Acuity” (BCVA) and Decrease of Central Macular Thickness (CMT) at Month 12

Improvement in BCVA (in Terms of Letter Gain) and Decrease in CMT (µm) from Baseline to Month 12	RBZ + Laser	BVZ + Laser	p-value
Mean change in BCVA in RBZ+Laser, (n = 77) and BVZ+Laser (n = 51) group	6.87±5.53	6.82 ± 5.76	0.858
Mean change in BCVA among moderate NPDR+Focal DME subjects (RBZ+Laser, n = 40; BVZ+Laser, n = 25)	11.30±3.603	11.96±3.020	0.540
Mean change in BCVA among severe NPDR+Diffused DME subjects (RBZ+Laser, n = 24; BVZ+Laser, n = 15)	3.125±2.232	3.200±2.455	0.801
Mean change in BCVA among PDR+Diffused DME subjects (RBZ+Laser, n = 24; BVZ+Laser, n = 15)	0.153±0.3755	0.090±0.301	0.999
Mean change in CMT (µm) in RBZ+Laser, (n = 77) and BVZ+Laser (n = 51) group	140.1±38.00	134.9±40.32	0.300
Mean change in CMT (µm) among moderate NPDR+Focal DME subjects (RBZ+Laser, n = 40; BVZ+Laser, n = 25)	171.9±3.770	170.6±3.830	0.192
Mean change in CMT (µm) among severe NPDR+Diffused DME subjects (RBZ+Laser, n = 24; BVZ+Laser, n = 15)	122.3±7.097	120.1±7.869	0.375
Mean change in CMT (µm) among severe PDR+Diffused DME subjects (RBZ+Laser, n = 24; BVZ+Laser, n = 15)	75.08±20.54	74.18±20.84	0.9168

Notes: Data were presented as mean ± SD. Normally distributed variables of two groups were compared by unpaired Student’s t-test. Not-normally distributed variables of the two groups were compared by the Mann–Whitney U-test. No significant differences were observed in the recovery of VA and decrement of CMT when compared RBZ+Laser group with BVZ+Laser groups. A value of p < 0.05 was considered statistically significant.

Abbreviations: BCVA, best-corrected visual acuity; CMT, central macular thickness.

Table 3 Showing the Adverse Events Related to Intravitreal Ranibizumab (RBZ) and Bevacizumab (BVZ)

Adverse Events	RBZ + Laser (n = 77)	BVZ + Laser (n = 51)	p-value
Arterial thromboembolic events	0	0	-
Angina pectoris	1 (1.29%)	1 (1.90%)
Pulmonary embolism	0	0
Cerebrovascular accident	0	0
Myocardial infarction	0	0
Hypertension	2 (2.59%)	1 (1.90%)
Non-ocular hemorrhage	0	0
Vitreous hemorrhage	0	1 (1.90)
Retinal detachment	0	0
Endophthalmitis	0	0
Raised IOP	0	1 (1.90)
Ocular pain	3 (3.89%)	3 (5.88%)
Total number of subjects with different kinds of adverse event	6 (7.79%)	7 (13.72%)	0.276
Number of subjects with no adverse events	71 (92.20%)	44 (86.27%)

Notes: Categorical variables in two groups were presented as percentages (%) and compared by the Chi-Square test. In the RBZ + Laser treated group 7.79% of subjects (1.29% angina pectoris, 2.59% hypertension, and 3.89% ocular pain) were found to be associated with different types of adverse events. In the BVZ + Laser treated group, 13.72% of subjects (1.90% angina pectoris, 1.90% hypertension, 1.90% vitreous hemorrhage, IOP raised among 1.90% and 5.88% subject experienced ocular pain) were found to be associated with different types of the adverse event. The rest 92% in RBZ + Laser treated group and 86.27% subjects in BVZ + Laser treated group experienced no adverse events. Subjects with adverse events and subjects without adverse events showed no significant distributional difference (p = 0.276) between the groups. A value of p < 0.05 was considered statistically significant.

Abbreviation: IOP, intraocular pressure.

Table 4 Levels of Different Biochemical Parameters After 12 Months

Parameters	RBZ+Laser Treated Group	BVZ+Laser Treated Group	p-value
HbA1C (%)	7.97±2.92	8.14±2.77	0.7426
PBMC ROS (Geo mean of DCF/ 10^5 cells)	100.7 ± 10.63	98.54 ± 16.28	0.5112
Serum AGE Conc. (µg/mL)	3.146 ± 0.66	3.02 ± 0.803	0.3068
Serum MDA Conc. (nmol/mL)	2.736 ± 0.4948	2.649 ± 0.6435	0.7293

Notes: Data were presented as mean ± SD. Not-normally distributed variables of two groups were compared by unpaired Mann Whitney U-test. The study showed no significant differences in HbA1c, PBMC ROS, AGE, and MDA between study groups. A value of p < 0.05 was considered statistically significant.

Abbreviations: PBMC, peripheral blood mononuclear cells; ROS, reactive oxygen species; DCF, Dichlorodihydrofluorescein Diacetate; AGE, advanced glycation end product; MDA, malondialdehyde.

Table 5 Distribution of Subjects with and without Clinically Significant Diabetic Macular Edema (CSDME) After 12 Months of Different Treatment Groups

Presence or Absence of CSDME	RBZ+Laser Treated Group	BVZ+Laser Treated Group	p-value
Presence	28 (36.36%)	22 (43.13%)	0.464
Absence	49 (63.63%)	29 (56.86%)

Notes: Categorical variables in two groups were presented as percentages (%) and compared by the Chi-Square test. In the RBZ + Laser treated group 28 (36.36%) and 49 (63.63%) subjects were found with CSME and without CSDME respectively after 12 months. In the BVZ+Laser treated group 22 (43.13%) and 29 (56.86%) subjects were found with CSDME and without CSDME respectively after 12 months. The statistical analysis showed no statistical difference in subjects distribution between the groups. A value of p < 0.05 was considered statistically significant.

Table 6 Cost-Effective Regimen

Number of Subjects (RBZ + Laser Group)	Number of Subjects BVZ + Laser Group	Average Letters Gain (RBZ + Laser Group)	Average Letters Gain (BVZ + Laser Group)	Cost of Treatment/Subject in INR (RBZ + Laser Group)	Cost of Treatment/Subject in INR (BVZ + Laser Group)	Cost in INR/Letter Gain/ Subject (RBZ +Laser Group)	Cost in INR /Letter Gain/Subject (BVZ +Laser Group)	Cost Increment (Times in INR)/Letter Gain/Subject
77	51	6.87	6.823	52,500	1648.35	99.245	4.737	20.951 times

Notes: Cost-effectiveness was calculated in terms of cost increment (times in Indian national rate or INR)/letter gain/subject = [Cost in INR/letter gain/ subject (RBZ +Laser group)]/[Cost in INR /letter gain/subject (BVZ +Laser group)]. The study showed that a subject has to pay 20.951 times more cost for a letter gain for RBZ + Laser therapy than the BVZ + Laser therapy.