Intravitreal sirolimus with adjunct aflibercept versus aflibercept monotherapy for persistent, exudative age-related macular degeneration
NCT02732899 | Not specified | Rowe LW et al. (2023)
Rowe LW, Minturn RJ, Burgett LA, Bracha P, Maturi RK. Intravitreal sirolimus with adjunct aflibercept versus aflibercept monotherapy for persistent, exudative age-related macular degeneration: a pilot study. Int J Retina Vitreous, 2023; 9:1.
Locations
Conducted in the United States
Study Period
April 12, 2016 – March 20, 2017
Study Design
Phase 2, single-center, randomized, subject-masked, controlled trial
Study Population
Experimental Group
Control Group
Follow-up Time: 36 weeks
Outcomes
Durability
Not reported
Vision
Best-Corrected Visual Acuity (BCVA) The mean change in BCVA change (ETDRS letters) from baseline to Week 36:
• Sirolimus + aflibercept: +2.5 (95% CI : -0.7 to 5.7)
• Aflibercept: +0.8 (95% CI : -1.3 to 2.9)
• Difference : p=0.42
Other
N/A
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Central Subfield Thickness (CST)
Mean change in CST from baseline to Week 36 (Primary Outcome):
• Sirolimus + aflibercept: -54.0 µm (95% CI : -106.7 to -1.4)
• Aflibercept: -0.1 µm (95% CI : -73.1 to 72.9])
• Difference : p= 0.28
The percentage decrease in mean CST :
• Sirolimus + aflibercept: 12%
• Aflibercept: 2.5%
• Difference : p= 0.30
Retinal Fluid
Mean change in subretinal fluid (SRF) from baseline to Week 36:
• Sirolimus + aflibercept: -9.32 mm³
• Aflibercept: -3.02 mm³
• Difference: p= 0.54.
The mean change in intraretinal fluid (IRF) from baseline to Week 36:
• Sirolimus + aflibercept: -0.43 mm³
• Aflibercept: -0.99 mm³
• Difference: p=0.60
Proportion of eyes with complete resolution of SRF from baseline to Week 36:
• Sirolimus + aflibercept: 22.2%
• Aflibercept: 30.0%.
Proportion of eyes with complete resolution of IRF from baseline to Week 36:
• Sirolimus + aflibercept: 67.0%
• Aflibercept: 33.0%
Safety
Minor ocular AEs
• Sirolimus + aflibercept: 4 events
• Aflibercept: 2 events.
Minor systemic AEs
• Sirolimus + aflibercept: 4 AEs
• Aflibercept: 2 AEs.
Serious ocular AEs
None reported in either group.
Serious systemic AEs
• Sirolimus + aflibercept: 3 events (pancreatitis, pneumonia, worsening hypertension)
• Aflibercept: 0 events.
Conclusion
Intravitreal sirolimus with adjunct aflibercept showed anatomical benefits, including greater CST reduction and improved IRF/SRF resolution. However, these improvements were not statistically significant, and there were more systemic adverse events in the sirolimus group. Further studies are needed to clarify the benefit-risk profile.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Some concerns
Note: No information on the randomization method. However, the two groups were comparable at the baseline.
Missing Outcome Data
Low risk
Note: The only missed visit by a subject occurred at week 32 in the control group and was deemed to be non-related to the subject’s ocular disease or treatment.
Selection of the Reported Results
Low risk Registration with the protocol.
Deviations from Intended Observations
Low risk Note: The assessors and the patients wee masked to the study treatment. “No subjects in the control group met deferral of treatment criteria at any point during this trial.” All 20 patients were included to the final assessment. (ITT principle)
Measurement of the Outcome
Low risk Note: this is a single site study. “The same Heidelberg Spectralis machine was used to obtain both images and CST. Prior to data analysis, the automated CST segmentation was verifed and manually adjusted in an anonymized manner, as necessary.”
Overall
Some concerns
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