A Finnish study, led by researchers at the Tays Eye Centre, Tampere University Hospital, Finland, has shown that results of anti-VEGF treatment for neovascular AMD, in a real world clinical population, do not appear to be as positive as results from previous randomized controlled trials (RCTs). The Finnish study assessed data from 1,349 eyes in 1,117 patients encompassing a total of 11,562 intravitreal anti-VEGF injections. The results indicated that study subjects had a mean baseline Snellen visual acuity (VA) of 0.32 and, following treatment, had a mean change of VA from baseline of +2, +2 and ±0 ETDRS letters with a mean number of injections of 5.7, 4.7 and 4.9 at years 1, 2 and 3, respectively. In contrast, the researchers had noted VA gains of 6-11 ETDRS letters with certain anti-VEGF agents at 2 year follow up in RCTs.
Differences between clinical trial studies and subsequent post-approval real world evidence are well documented in the literature. As a result, a growing number of researchers, industry personnel and national regulators are working to incorporate more real world evidence into drug research activities. The reasons for the different outcomes arise from a number of differences between clinical trial protocols and the profile of patients presenting in clinics for treatment. Clinical trial protocols generally have strict inclusion and exclusion criteria and have dosing and treatment regimens which may be difficult to replicate in the setting of a busy clinic. VA gains of 6-11 ETDRS are understood to have been achieved following fixed monthly ranibizumab (Lucentis) and bevacizumab (Avastin) and bimonthly aflibercept (Eylea) (after 3 monthly injections) treatments, as well as a pro re nata (PRN) regimen.
In the Finnish study, although the VA was maintained, the initial gain in acuity was lower than in clinical trials that had used fixed monthly treatment and/or monitoring. In their study report the researchers stated that bevacizumab is the most commonly used anti-VEGF drug for neovascular AMD in Finland due to its affordability. Bevacizumab accounted for 94% of injections in the observational study and, consequently, the researchers point out that their study may be more accurately described as a real-life outcome of bevacizumab in neovascular AMD. According to the researchers, the PRN treatment protocol appears “more cost-effective than monthly bevacizumab, as small increases in effects incur higher additional costs”, and that “bevacizumab appears more cost-effective than ranibizumab and aflibercept given as needed or monthly”.