Discussion
This 12-month interim analysis of the RAINBOW study showed that visual and anatomical improvements were achieved in treatment-naïve patients with wet AMD receiving IVT-AFL in a real-world setting. The outcomes observed in patients who received a loading dose (first three injections within 90 days) were favourable compared with those achieved in randomised studies. In the VIEW studies, the mean change in BCVA was 8.4 letters, the percentage of patients gaining ≥15 letters was 30.9% and the percentage of patients maintaining visual acuity (losing <15 letters) was 95.3% at month 12 in the combined IVT-AFL 2 mg bimonthly group (2q8) after three loading doses.6 These patients received ~7.5 IVT-AFL injections over 12 months. There were, however, some differences in baseline characteristics between RAINBOW and VIEW. The mean age and baseline BCVA were both higher in RAINBOW than VIEW, and the BCVA was outside the VIEW inclusion criteria in about 20% of patients enrolled in RAINBOW (<25 letters in 7.9% and >73 letters in 13.2%, respectively). The IVT-AFL regimen in the RAINBOW study was also different from VIEW, with only 10% of patients receiving the same protocol. Another observational study in the UK, which monitored treatment-naïve patients with wet AMD (58 eyes) receiving IVT-AFL bimonthly treatment (after a loading dose), reported similar visual outcomes to RAINBOW.11 The baseline BCVA was 54.1 ETDRS letters, and the mean improvement in BCVA was 4.67 letters at month 12; 17.2% of patients gained ≥15 letters, and 96.6% of patients avoided losing >15 letters at month 12. The mean reduction in CRT was lower (–35.36 µm) than in RAINBOW, but the baseline CRT was also lower (284.2 µm). The mean number of IVT-AFL injections was similar (7.1), but the mean number of clinical visits was lower (4). These authors used fixed IVT-AFL dosing. The IVT-AFL regimen used in RAINBOW was more variable and may warrant further investigation.
RAINBOW also highlighted an improvement in outcomes with IVT-AFL compared with earlier observational studies (such as AURA) that monitored ranibizumab.7 There may be a number of reasons for this, including improvements in patient management (a number of ranibizumab studies were published several years ago) and differences in dosing regimens between the two agents. For example, in the AURA study, which monitored outcomes in 2227 patients with wet AMD, visual acuity declined over time to 2.4 letters at year 1 and 0.6 letters at year 2, and the mean number of ranibizumab injections was 5.0 at year 1 and 2.2 at year 2.7 In the French cohort of AURA, which comprised 398 patients, the mean change in visual acuity was 0.8 letters at year 1 and –1.1 letters at year 2, the mean number of ranibizumab injections was 4.4 (year 1) and 1.9 (year 2), and the mean number of visits was 8.5 (year 1) and 4.9 (year 2). More recent ranibizumab studies have reported variable results. A larger analysis of 18 358 eyes from 20 real-world studies also found that outcomes did not reflect those reported in randomised studies. In this analysis, the mean change in visual acuity was 2.9 letters at year 1 and the mean number of ranibizumab injections was 5.5.8 In comparison, interim findings from the ongoing LUMINOUS study showed that the mean change in BCVA was 4.4 letters at month 12, and the mean number of ranibizumab injections was 4.7 in 706 treatment-naïve patients with wet AMD.10 A recent meta-analysis of ~26 360 patients from 42 real-world studies reported better outcomes with ranibizumab T&E compared with as-needed, which was used in some earlier studies. The mean change in visual acuity was 8.8 versus 3.5 letters and the mean number of injections was 6.9 versus 4.7 at year 1, respectively.9 Unfortunately, outcomes by IVT-AFL regimen (as-needed, T&E or observe and plan) were not explored in this interim analysis of RAINBOW.
RAINBOW also showed that IVT-AFL was well tolerated in clinical practice. However, the incidence of ocular AEs was generally lower in RAINBOW than in VIEW, which may be due to differences in reporting of AEs between randomised and observational studies, with the possibility of under-reporting. These findings were; however, consistent with the known safety profile of IVT-AFL in wet AMD.5 6
It must be noted that there are a number of limitations inherent with the observational design of the RAINBOW study. Evaluation of visual acuity was performed using EDTRS letter charts or any other visual scale in this study. However, the use of different charts may introduce bias, especially in the measurement of the number of letters gained or lost after treatment. The findings are also based on one European country, which may not be representative of other European countries and their respective reimbursement strategies.
In conclusion, this 12-month analysis highlights the effectiveness and safety associated with IVT-AFL in treatment-naïve patients with wet AMD in routine practice. Patients who received a loading dose also experienced better outcomes at month 12, although the correlation needs to be established by a multivariate analysis as these patients also received a mean of 0.6 more IVT-AFL injections. Ocular TEAEs were also consistent with the known safety profile of IVT-AFL. RAINBOW showed that outcomes achieved with IVT-AFL (after a loading dose) in randomised studies, such as VIEW, can be achieved in a real-world setting.