A treat-and-extend approach to management of neovascular age-related macular degeneration (AMD) better suits the needs of patients in the ‘real world’, Jennifer Arnold, Retinal Specialist, Sydney, Australia, told a session of the 16th EURETINA Congress in Copenhagen, Denmark.
“Real-world outcomes are often not as good as those obtained in the large randomised, controlled trials. This is very likely due to undertreatment of the neovascular lesions for one reason or another,” said Dr Arnold.
Early in the development of anti-vascular endothelial growth factor (anti-VEGF) treatment, monthly therapy with ranibizumab was the only evidence-based management strategy. Studies such as the PIER and EXCITE trials, in an attempt to reduce treatment frequency, revealed the inferiority of regular, quarterly injections following three initial monthly injections.
Later studies such as the CATT trial supported the efficacy of individualised, PRN treatment as compared to monthly treatment, but the financial and logistical burden of monthly monitoring visits remained.
Real-world outcomes are often not as good as those obtained in the large randomised, controlled trials
OPTIMISE VISUAL OUTCOMES
Richard Spaide MD and K Bailey Freund MD first proposed the treat-and-extend management protocol as a way to optimise visual outcomes and safety while keeping visits, injections and recurrences to a minimum.
Treat-and-extend involves a “loading phase”, consisting of monthly anti-VEGF injections until the macula is “dry”, followed by treatment intervals that progressively increase in duration between visits, up to a maximum of 10 to 12 weeks. A full assessment is conducted, and an intravitreal injection is administered, at each office visit.
The interval between visits depends on lesion activity. If clinical or optical coherence tomography evidence suggests early recurrence, or persistence, of macular exudation, the interval between treatments is shortened. It is, in effect, a personalised PRN regimen.
“Real-world PRN treatment strategies tend to treat patients too late,” said Dr Arnold. She referred to three studies published within the past two years to support her point.
Tufail et al performed an audit of more than 11,000 patients treated in the UK within a pure PRN regimen. This study reported a very modest increase of two letters after five injections at one year, one letter (four injections) at two years, and then a decrease of two letters (four injections) at three years.
Another retrospective chart review, the AURA study conducted by Holz et al, regarding more than 2,200 Europeans patients on a PRN regimen, reported similarly weak visual results, with vision increase of 2.4 at one year (five injections) and 0.6 at two years (2.2 injections).
The third study was a meta-analysis by Kim et al of the real-world outcomes of over 26,000 patients from 42 observational studies (2007-2015). This study reported a large 7.3-letter difference in visual acuity change at three years between treat-and-extend (5.4-letter increase) and PRN (1.9-letter decrease). Patients in the treat-and-extend group received a mean of 6.9 yearly injections over the three-year period, while those in the PRN group received an average of 4.7 injections per year.
“Clearly, a treat-and-extend regimen can deliver better patient outcomes,” said Dr Arnold.
To back this up, Dr Arnold shared the results of her group’s study, Two-Year Outcomes of ‘Treat and Extend’ Intravitreal Therapy for Neovascular Age-Related Macular Degeneration, published in Ophthalmology in 2015. This data for this study of 1,198 treatment-naïve eyes, treated primarily with ranibizumab and followed up for 24 months, was gathered via a real-world prospective data audit tool organised by the Fight Retinal Blindness Study Group.
“This pooled data set demonstrated a mean visual acuity increase of 5.3 letters at 24 months. This required an average of 13.0 injections spread over 14.6 clinic visits,” she said.
Treat-and-extend encompasses two phases: induction, which involves monthly treatment until the lesion becomes inactive; and maintenance, which involves the treat-and-extend strategy.
Dr Arnold emphasised that the time to achieve lesion inactivity can be highly variable between patients.
“The median time to lesion inactivity is 15 weeks. Some 11% become inactive after one injection, and 61% after three injections. However, 6% require more than 12 injections to reach inactivity, and 15% never become inactive,” she said.
Another study by Dr Arnold’s group focused on the maintenance phase, looking at treatment interval differences. According to the data, 20% of patients require monthly injections and 55% require injections every six to eight weeks. The remaining 25% can go 12 weeks or more without treatment, although extending too long between injections increases the risk of reactivation, she warned, especially if extended for 16 or more weeks. One in five patients reactivated at intervals of 16 weeks or longer.
“Treat-and-extend can achieve acceptable outcomes in an unselected patient group treated in routine clinical practice, as long as we treat intensively until lesions are inactive, and remain very vigilant to detect recurrences early,” she concluded.
Jennifer Arnold: firstname.lastname@example.org