The results of long-term use of aflibercept in patients with macular edema has inidcated that the need for retreatment appears to be substantially reduced in the fourth and fifth years of dosing, following initiation of therapy in a pivotal clinical trial. Researchers based at a number of US retinal clinics reported their findings in the British Journal of Ophthalmolgy, stating that vision gains achieved during the first 3 years of the drug’s clinical trial were maintained in a follow-up Phase IV study. However, researchers additionally reported a clinically relevant worsening of diabetic retinopathy, which was observed to progress to PDR in 10% of the eyes.
The researchers conducted the Phase IV, 2-year, open-label extension study in 3 centres in the US, recruiting sixty patients in total. The study, referred to as the Endurance Trial, was designed to assess the need for ongoing intravitreal aflibercept injections after a previous 3-year study (VISTA-DME). Subjects, who had previously participated in the VISTA-DME study, were treated with intravitreal aflibercept injections pro re nata (PRN) based on the presence of clinically relevant DME. Intervals between visits were prescribed according to disease activity and the main outcome measure was the mean number of aflibercept injections given over the 2-year study period. Analysis of the results showed that a mean of 7.7 aflibercept injections were administered during the study, with 25% of patients requiring no retreatment and 48% receiving five or fewer injections. Among patients who received at least one aflibercept retreatment during the 2 year period, the mean number of injections by the end of the study was 9.5. According to the researchers, the mean visual acuity (VA) and central retinal thickness (CRT) gains achieved in the original VISTA DME trial were maintained and stable during the follow up Phase IV. Notwithstanding such, the most notable safety signal was progression of diabetic retinopathy where 10% patients converted from non-proliferative to proliferative diabetic retinopathy (PDR).
In conclusion, a clinically meaningful proportion of patients – 25% – may be said to have maintained visual and anatomic gains without the need of re-treatment while the remaining 75% required at least one additional retreatment. Regardless, the outcomes demonstrated positive efficacy over a 5-year period which will be encouraging for both clinicians and patients as they seek to optimise treatment regimens. The finding is additionally consistent with previous reports whereby patients maintain quiescent disease once stability is achieved. In summarising their findings the investigators of the study stated that, “[O]n a population basis, the long-term management burden through 5 years for patients with DR and DME appears to be substantial. While a clinically relevant minority of patients will not need anti-VEGF dosing for DME, the majority of patients require ongoing clinical evaluation and repeated treatments.”