Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR
NCT01213082 | Not specified | Mukkamala LK et al. (2020)
Mukkamala LK, Mishra K, Daftari I, Moshiri A, Park SS. Phase I/II randomized study of proton beam with anti-VEGF for exudative age-related macular degeneration: long-term results. Eye, 2020; 34:2271–2279.
Locations
Single-center study at University of California Davis Eye Center, USA
Study Period
October 2010 – January 2015
Study Design
Phase I/II, randomized, double-masked, sham-controlled, single-center study
Study Population
Experimental Group
Control Group
Follow-up Time: 24months
Outcomes
Durability
Number of Injections The mean number of anti-VEGF injections over 24 months (co-primary outcome):
• 24 GyE PBT: 4.1 ± 1.9
• 16 GyE PBT: 7.8 ± 2.2
• Sham: 10.3 ± 3.8
• 24 GyE vs. Sham: p=0.002
• 16 GyE vs. Sham: p=0.217 The mean number of anti-VEGF injections over 12 months :
• 24 GyE PBT: 3.1 ± 1.2
• 16 GyE PBT: 4.8 ± 1.3
• Sham: 6.4 ± 1.3
• 24 GyE vs. Sham: p<0.001
• 16 GyE vs. Sham: p=0.058
Vision
Best-Corrected Visual Acuity (BCVA) (primary outcome) There was no significant difference in the mean BCVA among the three treatment groups at baseline, 1-year, and 2-year follow-up. Vision Maintaining No eye experienced severe visual loss (loss of >15 letters) within 2 years.
Other
Geographic Atrophy (GA) Rate of GA growth (mm²/year):
• 24 GyE PBT: 0.34±0.31
• 16 GyE PBT: 0.08±0.19
• Sham: 0.07 ±0.27
• 24 GyE vs. Sham: p=0.17
• 16 GyE vs. Sham: p=0.95
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Choroidal Neovascular Membrane (CNVM)
• The mean size of the CNVM at baseline and at 2 years follow-up for the study groups were not significantly different (ANOVA: p = 0.50 at baseline; p = 0.21 at 2 year)
• There was no difference in mean severity of leakage among the study groups at baseline and 2-year follow-up (p > 0.05).
• Eyes in the 24 GyE group had the largest proportion of eyes with most severe leakage at baseline and the highest proportion of eyes without leakage at 2-year follow-up Retinal Fluid Patients proportion without intraretinal or subretinal fluid on OCT at 2 years:
• 24 GyE PBT: 80%
• 16 GyE PBT: 60%
• Sham: 25%
• The difference was not significant (p = 0.064) Central macular Thickness (CMT) The mean change of CMT at 2 years:
• 24 GyE PBT: -144µm
• 16 GyE PBT: -121µm
• Sham: -37µm
• The difference among groups was not statistically significant (p = 0.255)
Safety
Ocular AEs Patients with mild radiation retinopathy:
• 24 GyE PBT: 15%
• 16 GyE PBT: 10%
• Sham: 0%. Serious AEs (SAEs)
• No eye experienced severe visual loss (loss of >15 letters) within 2 years. Non-ocular AEs Not reported
Conclusion
24 GyE PBT combined with anti-VEGF significantly reduced the need for anti-VEGF injections compared to sham radiation but was associated with a non-significant trend toward increased geographic atrophy. Long-term safety was acceptable with mild radiation retinopathy.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “Randomization was based on sequential coin tosses performed by an unmasked study coordinator.” “The three groups were similar.”
Missing Outcome Data
High risk
Note: The dropout rate was (0% vs. 50% vs. 20%). There is no information on whether the missingness depend on the true value or not. However, likely it is depend on the true value.
Selection of the Reported Results
Low risk Note: the protocol was publicly available
Deviations from Intended Observations
High risk Note: This is a double-masked study. The analysis was based on the per-protocol principle (not appropriate). The dropout rate was (0% vs. 50% vs. 20%), and there was potential for a substantial impact (on the result) of the failure to analyze participants in the group to which they were randomized.
Measurement of the Outcome
Low risk Note: This is a double-masked study in a single study site.
Overall
High risk
Categories: Wet AMD