To our knowledge, and based on the medical literature, STELLAR provides the first retrospective observational data describing the use of IVT-AFL in clinical practice in Belgium. During the 4-year observation period (2013–2017), there was a shift in treatment regimens from reactive (i.e. PRN) to proactive treatment using a T&E regimen. More than half (64%) of patients received ≥ 7 injections during the first year of treatment. Overall, treatment with IVT-AFL was effective, with patients gaining an average of 3.9 ETDRS letters after the first 3 months and 5.7 ETDRS letters after 1 year of IVT-AFL treatment. Although definitive conclusions cannot be drawn since groupings occurred post-baseline, we did observe a greater improvement in visual acuity in patients who received ≥ 7 injections in the first year of IVT-AFL treatment and those who received three injections during the first 3 months of IVT-AFL compared with patients who did not.
Despite IVT-AFL being launched in Belgium with a fixed-dose regimen for the first 12 months of treatment (three monthly injections followed by an injection every 8 weeks), IVT-AFL was administered in this manner in only 5% of patients on average over the 4-year observation period. In fact, in the first year of observation (2013–2014), IVT-AFL was most commonly administered PRN. The use of the PRN strategy is likely due to the previous experience of investigators with ranibizumab and may account for the mean number of treatment visits being higher than the mean number of injections, as PRN treatment often requires more monitoring visits than injections. The reasons for patient visits (i.e. treatment, monitoring, other) were, however, not collected during the study.
The T&E protocol is now widely used and can minimize the financial costs and patient burden associated with the need for frequent treatment [18]. Using a T&E regimen, patients with nAMD can maintain stable visual function over 4 years in real-world clinical practice [19]. In STELLAR, by 2015–2016, the T&E strategy was the most commonly used approach for a patient’s first year of treatment, but it was not until 2018 that IVT-AFL formally received the product licence extension endorsing the T&E treatment protocol within the first year after three initial monthly doses and an injection 8 weeks later at week 16.
The proportion of patients who received ≥ 7 injections during the first 12 months of treatment in STELLAR in Belgium (64%) was higher than that observed in the French RAINBOW study of treatment-naïve patients and German PERSEUS study of treatment-naïve and previously treated patients, in which 46 and 32% of patients, respectively, received ≥ 7 injections [14, 16]. When making this overall comparison, we note that PERSEUS and RAINBOW, in which patients initiated treatment in 2013–2015 and 2014–2015, respectively, were conducted earlier than STELLAR. However, data from comparative years of STELLAR also indicate that a larger proportion of patients received ≥ 7 injections in Belgium (48% in 2013–2014 and 60% in 2014–2015). The observation of patients receiving 8–10 or more injections in the first year is also consistent with other observational studies [14, 16]. We also noted that only 12 patients (3%) who completed 12 months of treatment in STELLAR had not received three monthly injections of IVT-AFL, compared to approximately 20% of patients who did not receive the initial three monthly doses in RAINBOW and PERSEUS [14, 16]. Further investigation of these patients found that the reasons for not completing three injections within the first 3 months were varied and included (1) organizational and logistical reasons, which resulted in longer intervals between first three injections and thus the patient not receiving the three injections in a 3-month period; (2) the disease being considered inactive by the treating physician, resulting in follow-up on a reactive PRN basis; and (3) a consequence of comorbidities, such as a delay in injections because of intervening cataract surgery. It was interesting to observe that this small subgroup of patients had a numerically higher BCVA than other patients in the STELLAR study; however, the small number of patients limits the certainty of conclusions that can be drawn regarding BCVA changes in this subgroup.
Although patients were enrolled prospectively in RAINBOW and PERSEUS, STELLAR was a retrospective review in which patients had to have completed 12 months of treatment to be included in the analysis. This study design introduced a selection bias, as patients treated for shorter periods for various reasons were not analysed. In addition, the discontinuation rate after 12 months of treatment (18%) was lower than expected (25%), which could suggest that the investigators’ selection of patients for enrolment was biased toward those patients who completed the first 12 months.
It is generally accepted that, in regular clinical practice, patients with nAMD receive fewer anti-VEGF injections and have smaller gains in visual acuity than do patients in randomized controlled trials. Consistent with this, patients enrolled in the VIEW studies had larger increases in BCVA from a lower baseline level compared with those in STELLAR [8]. Comparing data across other observational studies, the mean baseline visual acuity in the RAINBOW and PERSEUS studies (53.4–56.7 letters) was lower than in the STELLAR study. This provides greater opportunity for improvements from baseline to be demonstrated; however, the mean visual acuity letter gain at 12 months in STELLAR (+ 5.7 letters) was comparable to that reported in those studies (+ 5.3 to 5.5 letters) [14, 16]. Similarly, in a retrospective observational study of IVT-AFL in the UK, at 12 months, mean BCVA improved by + 5.0 letters from a mean baseline of 56.3 letters [12]. It is known that older age, better baseline BCVA and larger choroidal neovascularization lesion size are independently associated with lower mean BCVA gains after anti-VEGF therapy [20, 21]. However, aside from baseline visual acuity, no other baseline disease characteristics or patient demographics were collected in STELLAR. It is therefore unknown whether such differences in patient populations account for differences between STELLAR and other studies.
Despite the limitations described, one particular strength of our study is that data were collected from eight centres, which ensured geographical representativeness of findings and allowed enrolment of a robust number of patients. Although it is difficult to draw overall conclusions encompassing the entire Belgian population of patients with nAMD treated with IVT-AFL, STELLAR provides valuable information about IVT-AFL usage patterns and functional outcomes in clinical practice.