Variability in response to anti-VEGF therapy and definitions of response

“There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations.” (opens the source at this quote in a new tab)
“The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles.” (opens the source at this quote in a new tab)
“Non-response is defined as an increase in fluid (IRF, SRF and CRT), or increasing haemorrhage compared with the baseline and/or loss of >5 letters compared with the baseline or best corrected vision subsequently.” (opens the source at this quote in a new tab)

Baseline predictors of visual outcome and injection need: HARBOR

“Baseline predictors of BCVA change from baseline at M12 and/or percentage of 3-line gainers included lower BCVA, younger age, smaller total choroidal neovascularization (CNV) leakage area, smaller area of occult CNV, and presence of subretinal fluid (SRF).” (opens the source at this quote in a new tab)

Genetic background and choice of agent

“However, a systematic review published in 2015 looked at the association between anti-VEGF response and variations in AMD-associated genes; it concluded that genetic background may influence an individual’s response to treatment, however further studies are needed to better understand the contribution of various genes to treatment response.” (opens the source at this quote in a new tab)
“When used, the choice of biologic product (reference, biosimilar, or interchangeable) should be that of the treating ophthalmologist and the patient because patients may respond more favorably to one biologic over another.” (opens the source at this quote in a new tab)

Polypoidal choroidal vasculopathy subtype

“Polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative age-related macular degeneration among Asian individuals.” (opens the source at this quote in a new tab)
“Combination therapy was also superior to monotherapy in achieving complete polyp regression at month 12 (69.3% vs 34.7%; P < .001).” (opens the source at this quote in a new tab)

“Mean (95% CI) change from baseline to weeks 40/44/48 average was +8.9 (7.3-10.5) letters for BCVA and -126.5 (-144.8 to -108.3) μm for CST.” (opens the source at this quote in a new tab)
“At week 48, 83.4% (105/126) of patients were on ≥ Q12W dosing and 53.2% (67/126) were assigned to Q20W dosing.” (opens the source at this quote in a new tab)

Baseline disease severity and extended dosing with aflibercept 8 mg

“Patients in the aflibercept 8q12 and 8q16 arms achieved visual and anatomic outcomes at week 96 comparable to those in the aflibercept 2q8 arm within subgroups defined by baseline disease severity.” (opens the source at this quote in a new tab)

Real-world differences in treatment intensity by age and baseline vision

“Greater mean 1-year change in VA also trended with worse baseline VA; those patients with better VA at presentation tended to be particularly vulnerable to vision loss. Those who received the fewest injections tended to be older and have worse baseline VA.” (opens the source at this quote in a new tab)

Subgroup differences in brolucizumab inflammation risk

“Patients with a history of IOI and/or RO in the 12 months before brolucizumab initiation had an increased observed risk rate (8.7% [95% CI, 6.0%-11.4%] and 10.6% [95% CI, 7.5%-13.7%]) for an IOI and/or RO event in the 6 months following the first brolucizumab treatment compared with patients without prior IOI and/or RO (2.0% in both data sets).” (opens the source at this quote in a new tab)

4D-150 PRISM: treatment burden reduction by disease population

Cohort	Through year 1	Through year 1.5 (phase 2b) or year 2 (phase 1/2a)
Phase 2b subgroup: recently diagnosed	“94%”	“92%”
Phase 2b: broad	“83%”	“82%”
Phase 1/2a: severe, recalcitrant	“83%”	“79%”

4D-150 PRISM: comparators used for burden reduction differ by cohort

“Within the Phase 2b Phase 3 dose arm, a subgroup of 15 recently diagnosed patients were enrolled, which is most comparable to our Phase 3 population.” (opens the source at this quote in a new tab)

Subgroup efficacy results for 4D-150 by lesion subtype, genotype, or race

No evidence found.

Preexisting neutralizing antibody titers as a determinant of response and eligibility

“A critical consideration in future clinical development is the establishment of NAb threshold cutoffs to refine patient selection and increase trial success rates” (opens the source at this quote in a new tab)
“The implementation of standardized assays and validated NAb titer thresholds, exemplified by AAV6 enrollment assays that, through analyses of clinical trial data, demonstrate a correlation between preexisting NAb levels and transgene expression, enables more precise stratification of patients into likely responders and non-responders, thereby optimizing trial enrollment and minimizing variability in clinical outcomes” (opens the source at this quote in a new tab)

Transient immunosuppression to broaden eligibility in antibody-positive participants

“Combination therapy, such as transient systemic or local immunosuppression, represents a promising approach to enhance efficacy and expand patient eligibility in AAV-based gene therapy.” (opens the source at this quote in a new tab)
“This strategy can attenuate anti-capsid immune responses and has shown potential to enable transduction in NAb-positive subjects, and its use is increasingly explored in clinical settings” (opens the source at this quote in a new tab)

Lesion phenotype and risk factors for atrophy during anti-VEGF treatment

“Key risk factors or phenotypes associated with atrophy were fellow eye atrophy, reticular pseudodrusen, increased injections, and type 3 lesion.” (opens the source at this quote in a new tab)
“These phenotypes may explain why not all patients with AMD have the same atrophy-related outcomes.” (opens the source at this quote in a new tab)
“For example, patients with type 3 lesions typically demonstrate atrophy in parallel with anti-VEGF treatment; however, those with other lesion types may not demonstrate atrophy as readily with anti-VEGF therapy.” (opens the source at this quote in a new tab)

Sex distribution among reported cases of brolucizumab-associated retinal vasculitis

“From review of patient characteristics, all 12 patients in this series were women.” (opens the source at this quote in a new tab)
“Although this may be chance, a greater preponderance of noninfectious uveitis and autoimmune disorders occur in women, and this may play a role.” (opens the source at this quote in a new tab)

Two-year visual outcomes by baseline visual acuity in United States registry practice

“In all groups, eyes with better VA at baseline retained better VA at both Years 1 and 2” (opens the source at this quote in a new tab)
“Only groups of eyes with a mean VA of 20/40 or better at baseline maintained 20/40 or better vision 2 years after treatment initiation.” (opens the source at this quote in a new tab)
“Eyes with baseline VA of 37 to 23 letters (20/200-20/320) showed the greatest gain in VA at Year 1, improving to 0.37 ± 0.64 logMAR (20/160), and to 0.38 ± 0.68 logMAR (20/160) at Year 2.” (opens the source at this quote in a new tab)
“In contrast, mean VA declined slightly in the those with greater than 82 letters at baseline, from 0.03 ± 0.08 logMAR (> 20/25) to 0.14 ± 0.25 logMAR (20/32) at Year 1 and 0.18 ± 0.31 logMAR at Year 2 (20/32).” (opens the source at this quote in a new tab)

Racial composition and follow-up completeness of the registry cohort

“It should be noted that 97.5% of the evaluated population was white (which may not reflect the current racial makeup of the United States); the overwhelming percentage of white patients in this analysis suggests white patients may be more likely to seek diagnosis and treatment, or it may be reflective of socioeconomics and access to eye care in more racially diverse locations.” (opens the source at this quote in a new tab)
“Further, our 2-year data included only 54% of those included at baseline” (opens the source at this quote in a new tab)