Evicenter
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4D-150

Neovascular age-related macular degeneration

Regulatory submission
Not announced
Launch
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Last updated
180 sources

Product information and disease descriptionPlace of product in therapyApproaches to treatment

Care management intervention strategies

16 evidence topics · 12 sources

AAO Preferred Practice Pattern: treatment regimens and follow-up

“Initial treatment and follow-up with intravitreal anti-VEGF therapy should be at approximately 4-week intervals.” (opens the source at this quote in a new tab)

“There are numerous protocols: monthly or bimonthly injections, treat-and-extend, PRN, or personalized treatment interval. There is no consensus about the ideal treatment intervals with anti-VEGF agents, and the physician can tailor treatment on an individual patient basis.” (opens the source at this quote in a new tab)

“A continuous, variable dosing regimen that attempts to individualize therapy, commonly referred to as treat-and-extend, is frequently used in clinical practice as an alternative to the two treatment approaches above.” (opens the source at this quote in a new tab)

“The PRN regimens using ranibizumab appear to have efficacy and safety comparable to fixed monthly regimens over 1 year of treatment, but they do not maintain the initial visual gains with longer follow-up.” (opens the source at this quote in a new tab)

Monthly versus as-needed dosing: CATT

“Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive.” (opens the source at this quote in a new tab)

Monthly versus as-needed dosing: HARBOR

“However, all treatment groups demonstrated clinically meaningful visual improvement (+8.2 to +10.1 letters) and improved anatomic outcomes, with the PRN groups requiring approximately 4 fewer injections (6.9-7.7) than the monthly groups (11.2-11.3).” (opens the source at this quote in a new tab)

Treat-and-extend versus monthly dosing: CANTREAT

“By the end of month 24, 466 of the 580 randomized patients (80.3%) had completed the study and participants in the T&E arm received a mean of 17.6 injections compared with 23.5 injections for the monthly arm, for a difference of 5.9 injections and visits over 2 years (95% CI, 5.4-6.5; P < .001).” (opens the source at this quote in a new tab)

“The mean (SD) BCVA improvement was not worse with the T&E arm, 6.8 (14.1) letters vs 6.0 (12.6) letters, compared with the monthly arm (difference, 0.9; 95% CI, -1.6 to 3.3; P = .21).” (opens the source at this quote in a new tab)

Treat-and-extend versus PRN in the third year: TREX-AMD

“Upon transition to PRN, subjects randomised to monthly dosing experienced a decline in BCVA.” (opens the source at this quote in a new tab)

Regimen and long-term outcomes in routine practice

“Eyes from ANZ patients received more injections than eyes from Swiss subjects over 10 years (a median of 53 vs 42, respectively) from fewer visits with better disease control (proportion of visits with active disease: 38% vs 69%, respectively), suggesting a treat-and-extend regimen versus a pro re nata regimen (treatment given only when the lesion is active).” (opens the source at this quote in a new tab)

Structured regimens and retention in care

“Treat-and-extend (T&E) regimens showed lower LTFU than pro re nata.” (opens the source at this quote in a new tab)

“Interventions to improve access and personalize support are essential to reduce LTFU and preserve visual outcomes.” (opens the source at this quote in a new tab)

NICE guideline NG82: switching, observation, and stopping treatment

“Consider switching anti-VEGF treatment for people with late AMD (wet active) if there are practical reasons for doing so (for example, if a different medicine can be given in a regimen the person prefers), but be aware that clinical benefits are likely to be limited.” (opens the source at this quote in a new tab)

“Consider observation without giving anti-VEGF treatment if the disease appears stable” (opens the source at this quote in a new tab)

“Stop anti-VEGF treatment if the eye develops late AMD (wet inactive) with no prospect of functional improvement.” (opens the source at this quote in a new tab)

Management of poor or non-response

“Poor or non-response to anti-VEGF treatments requires re-evaluation of diagnosis and if necessary switch to alternative therapies including other anti-VEGF agents and/or with photodynamic therapy (PDT).” (opens the source at this quote in a new tab)

Home monitoring devices

“Electronic monitoring devices are now available to aid in the detection of neovascularization at an early stage.” (opens the source at this quote in a new tab)

Supplemental aflibercept in the 4FRONT trials

“Eylea (aflibercept) will be administered at applicable visits” (opens the source at this quote in a new tab)

Visits and injections in years three through five after treatment initiation

“The mean (SD) number of visits for AMD care between the end of the clinical trial and the Follow-up Study visit was 25.3 (13.3); with 8.0 (4.0) in Year 3, 7.2 (4.0) in Year 4, and 6.5 (4.0) in Year 5. The mean (SD) number of treatments was 15.4 (12.5) with 4.8 (4.0) in Year 3, 4.5 (3.8) in Year 4, and 4.0 (3.6) in Year 5.” (opens the source at this quote in a new tab)

“There were 96 (14.8%) patients who had no treatments between the end of the clinical trial and the Follow-up Study visit, with a mean (SD) of 12.5 (8.4) visits.” (opens the source at this quote in a new tab)

Treatment intensity and five-year visual outcome across cohorts

“In the Australian retrospective review, the mean number of injections over 5 years was 25 with mean visual acuity decreasing to 20/63.” (opens the source at this quote in a new tab)

“In contrast, the mean number of injections was 11 over 5 years in the Pan-American Study and the mean visual acuity at 5 years was 20/250.” (opens the source at this quote in a new tab)

“Thus, more frequent treatment, both in the initial 2 years and in later years appears associated with better long-term outcomes, and many patients require treatment through 5 years and beyond.” (opens the source at this quote in a new tab)

Switching between anti-VEGF agents after release from a trial protocol

“After release from the clinical trial protocol, more than half of the patients received a treatment other than the drug assigned to them in the clinical trial.” (opens the source at this quote in a new tab)

“Among the 328 patients assigned to ranibizumab, 46 (14.0%) had no treatments, 64 (19.5%) had treatments with only ranibizumab, and 218 (66.5%) had at least 1 other type of treatment” (opens the source at this quote in a new tab)

Injection burden of continuous compared with discontinuous dosing over two years

“Participants assigned to the continuous regimen were treated monthly thereafter.” (opens the source at this quote in a new tab)

“If retreatment was needed, a further cycle of three doses was given monthly.” (opens the source at this quote in a new tab)

RegimenMedian number of treatments over 2 years (interquartile range)
Continuous, every month“23 (21 to 24)”
Discontinuous, as needed“13 (8 to 17)”
Overall“18 (12 to 23)”
Trade-offs between continuous and discontinuous dosing

“Mortality was lower with continuous than discontinuous treatment (OR 0·47, 95% CI 0·22–1·03; p=0·05)” (opens the source at this quote in a new tab)

“Pooled data from the two trials shows that discontinuous treatment was inferior to continuous treatment for best corrected visual acuity.” (opens the source at this quote in a new tab)

“Conversely, the risk of geographic atrophy increased with continuous treatment.” (opens the source at this quote in a new tab)

“The increased risk of systemic SAEs and death with discontinuous treatment should probably outweigh the increased risk of new geographic atrophy that was recorded with monthly treatment.” (opens the source at this quote in a new tab)

“Continuous treatment also avoids the need to monitor disease activity on every visit.” (opens the source at this quote in a new tab)

“However, in the context of biological therapies, the possibility of immunological sensitisation with intermittent dosing needs to be considered.” (opens the source at this quote in a new tab)

“The association of monthly treatment with an increased rate of development of geographic atrophy was more consistent.” (opens the source at this quote in a new tab)

“In the IVAN study, 34% of eyes that received continuous (monthly) treatment developed geographic atrophy as compared with 26% in the discontinuous (PRN) group” (opens the source at this quote in a new tab)