Comparison of Two Different Treat-and-Extend Protocols with Aflibercept in Wet Age-Related Macular Degeneration: One-Year Results
EU Clinical Trials Register Number: 2015-001394-41/FI | | Taipale C et al. (2020) – one year
Taipale C, Lindholm J-M, Laine I, Tuuminen R. Comparison of Two Different Treat-and-Extend Protocols with Aflibercept in Wet Age-Related Macular Degeneration: One-Year Results. Acta Ophthalmol, 2020; 98:267–273.
Locations
Single-center study in Finland
Study Period
January 2016 – July 2017
Study Design
Prospective, randomized, open-label, single-center study
Study Population
Experimental Group
Control Group
Follow-up Time: 52 weeks
Outcomes
Durability
Treatment Interval Mean treatment interval at 12 months (weeks):
• T&Em: 8.5 ± 2.2
• T&Er: 10.3 ± 2.8
• Difference: p = 0.017 In the T&Er protocol, 12 of 25 eyes (48%) reached a 12-week treatment interval or beyond at 1 year. In the T&Em protocol, it was only possible to reach a 10-week treatment interval at 1 year. Number of Injections Total number of injections over 12 months:
• T&Em: 8.64 ± 1.58
• T&Er: 6.96 ± 0.79
• Difference: p < 0.001
Vision
Best-Corrected Visual Acuity (BCVA) The mean ± SD change in BCVA (ETDRS letters) from baseline to 12 months (primary outcome):
• T&Em: +10.3 ± 11.5
• T&Er: +11.4 ± 10.6
• Difference: p = 0.434 The mean ± SD BCVA (ETDRS letters) at 12 months:
• T&Em: 61.8 ± 14.0
• T&Er: 60.8 ± 12.4
• Difference: p = 0.774 Vision Maintaining The proportion of patients gaining ≥15 ETDRS letters:
• T&Em: 6 (24%)
• T&Er: 6 (24%) The proportion of patients gaining ≥10 ETDRS letters:
• T&Em: 13 (52%)
• T&Er: 11 (44%) The proportion of patients gaining ≥ 5 ETDRS letters:
• T&Em: 17 (68%)
• T&Er: 21 (84%) The proportion of patients losing ≥5 ETDRS letters:
• T&Em: 2 (8%)
• T&Er: 2 (8%) The proportion of patients losing ≥10 ETDRS letters:
• T&Em: 1 (4%)
• T&Er: 1 (4%) The proportion of patients losing ≥15 ETDRS letters:
• T&Em: 1 (4%)
• T&Er: 0
Other
Efficacy: Progression Outcome Recurrence Patients with recurrence at 1 year:
• T&Em: 16/25 (64%)
• T&Er: 12/25 (48%)
• Difference: p = 0.254 The mean ± SD number of recurrences per eye:
• T&Em: 0.48 ± 0.77
• T&Er: 0.84±0.99
• Difference: p = 0.017
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Central Subfield Macular Thickness (CSMT) The mean± SD change in CSMT (µm) at 12 months:
• T&Em: -194.3 ± 153.6
• T&Er: -194.2 ± 176.6
• Difference: p = 0.793 Foveal Thickness The mean± SD change in foveal thickness (µm) at 12 months:
• T&Em: -202.0 ± 172.1
• T&Er: -215.6 ± 193.5
• Difference: p = 0.997 Dry Macular (No retinal fluid) The mean ± SD time to achieve dry macula:
• T&Em: 17.2± 17.6 weeks
• T&Er: 19.7 ± 17.3 weeks
• Difference: p = 0.618 Patients achieved dry macula at 1 year:
• T&Em: 18/25 (72%)
• T&Er: 17/25 (68%)
• Difference: p = 0.758 Patients did not achieve dry macula at any time point during the first year of the study:
• T&Em: 3/25 (12%)
• T&Er: 4/25 (16%)
• Difference: p = 1.00
Safety
Treatment-emergent AEs
• No serious ocular and systemic adverse events or suspected unexpected serious adverse reactions were observed in any of the study subjects during the first year.
• One of the study eyes was subjected once (after the 1st intravitreal injection) and another one twice (after the 3rd and 8th intravitreal injections) to corneal abrasion. These did not affect the predetermined intravitreal injection intervals. Serious ocular AEs Non-ocular AEs
Conclusion
Both aflibercept treat-and-extend protocols resulted in similar visual and anatomical improvements over 12 months. The rapid extension protocol required fewer injections than the moderate extension protocol. No major safety concerns were observed.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Some concerns
Note: The method of allocation concealment was not supplied. However, the baseline characteristics of the two groups are comparable.
Missing Outcome Data
Low risk
Note: Two patients (2/52, 3.8%, less than 5% for each group) were excluded from the final analysis. However, the missingness was not depended on true value.
Selection of the Reported Results
Low risk Note: Registration with protocol
Deviations from Intended Observations
Some concerns Note: This is an open-labeled study. However, the paper provided the reasons for those who did not complete the study, which is not because of the trial context (low risk). Two patients (2/52, 3.8%, about 1.9% for each group) were excluded from the final analysis (therefore, (m)ITT was not applied). For the primary outcome (the number of injections, analysis of 25 eyes for each group), there should be no potential impact (some concerns).
Measurement of the Outcome
Low risk Note: Acknowledging the intervention should not impact the measurement for the primary outcome (the number of injections).
Overall
Some concerns
Categories: Wet AMD