Dataset Information

Impact of intravitreal aflibercept dosing regimens in treatment-naive patients with neovascular age-related macular degeneration: 2-year results of RAINBOW.

ABSTRACT:

Background

To review treatment outcomes from real-world data of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) injection.

Methods

RAINBOW (ClinicalTrials.gov, NCT02279537) is an ongoing, observational, 4-year study to monitor the effectiveness and safety of IVT-AFL in patients with nAMD in clinical practice in France. Treatment-naïve patients diagnosed with nAMD who had been prescribed IVT-AFL by their treating physician were eligible. The regimens of interest were regular treatment interval cohort (patients who received three initial monthly IVT-AFL injections followed by regular injections every 2 months) and two irregular treatment interval cohorts (with and without three initial monthly injections). Here we describe results at 24 months in patients according to IVT-AFL treatment regimen.

Results

The mean change in best-corrected visual acuity (BCVA) with IVT-AFL from baseline to 24 months was + 3.0 letters in the overall population (P < 0.05 vs baseline). The mean change was positive for the regular and irregular treatment interval cohorts with initial doses (+ 4.9 and + 4.0 letters, respectively; P < 0.05 vs baseline) and negative for the irregular treatment interval cohort without initial doses (- 2.5 letters; P = 0.365 vs baseline) at 24 months. The mean overall number of IVT-AFL injections over 12 and 24 months was 6.0 and 8.8, respectively. The most common ocular adverse events were lack of efficacy (6.3%), vitreous floaters (2.7%), and increased lacrimation (1.7%).

Conclusions

In the real-world RAINBOW study, visual outcomes observed at 24 months were consistent with results from the primary endpoint at 12 months. In this study, treatment-naïve patients who received three initial IVT-AFL doses and regular IVT-AFL treatment over the first 24 months experienced better visual outcomes than patients who received no initial doses and an irregular treatment regimen.

Trial registration

www.ClinicalTrials.gov (NCT02279537). Registered 29 October 2014.

SUBMITTER: Weber M

PROVIDER: S-EPMC7249443 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of intravitreal aflibercept dosing regimens in treatment-naïve patients with neovascular age-related macular degeneration: 2-year results of RAINBOW.

Weber Michel M Dominguez Marcel M Coscas Florence F Faure Céline C Baillif Stéphanie S Kodjikian Laurent L Cohen Salomon-Yves SY

BMC ophthalmology 20200525 1

<h4>Background</h4>To review treatment outcomes from real-world data of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) injection.<h4>Methods</h4>RAINBOW (ClinicalTrials.gov, NCT02279537) is an ongoing, observational, 4-year study to monitor the effectiveness and safety of IVT-AFL in patients with nAMD in clinical practice in France. Treatment-naïve patients diagnosed with nAMD who had been prescribed IVT-AFL by their treating phy ...[more]

PMID: 32450838

Similar Datasets

Project description:PurposeThe purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France.MethodsRAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45-90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here.ResultsOverall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and - 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies.ConclusionIn RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes.Trial registration numberClinicalTrials.gov Identifier: NCT02279537.

Project description:IntroductionXTEND (NCT03939767) is a multicenter, observational, prospective study of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in routine clinical practice. The study aims to examine treatment outcomes of proactive intravitreal aflibercept (IVT-AFL) treatment regimens (fixed dosing or treat-and-extend) according to local marketing labels.MethodsStudy eyes received IVT-AFL injections as per the local label. The mean changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month (M) 12 and M24 were measured and stratified by baseline factors. Treatment exposure and safety data were evaluated. Statistical analysis was descriptive.ResultsOverall, 1466 patients from 17 countries were treated. For the overall population, the mean ± standard deviation (SD) age was 78.7 ± 8.5 (range 50-100) years, and 891 patients (60.8%) were female. The mean ± SD baseline BCVA was 54.3 ± 20.3 letters and CST was 374 ± 126 µm. At M12 and M24, mean (95% confidence interval [CI]) BCVA change was + 4.3 (3.4, 5.3) and + 2.3 (1.3, 3.3) letters, respectively. Mean (95% CI) CST was - 106 (- 114, - 99) μm and - 109 (- 117, - 102) μm at M12 and M24, respectively. At M24, 41.5% of patients had a BCVA ≥ 70 letters. Patients received a mean ± SD of 7.7 ± 2.7 injections by M12 and 10.8 ± 5.0 injections by M24 (3.1 injections between M12 and M24). Adverse events were consistent with the known safety profile of IVT-AFL.ConclusionThe 24-month results indicate that, in routine clinical practice, a proactive IVT-AFL regimen achieves functional improvements in patients with treatment-naïve nAMD. The proportion of patients achieving ≥ 70 letters at M24 increased, and patients with baseline BCVA ≥ 70 letters maintained vision regardless of the followed IVT-AFL label.Trial registrationClinicalTrials.gov identifier: NCT03939767. A video abstract is available for this article. Supplementary file2 (MP4 364624 KB).

Project description:IntroductionAZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year.MethodsPatients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52.ResultsThe full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified.ConclusionIVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden.Trial registrationClinicalTrials.gov Identifier: NCT02540954.

Project description:BackgroundAnti-vascular endothelial growth factor (anti-VEGF) agents have become the standard of care in neovascular age-related macular degeneration (nAMD). Despite generally excellent response rates to anti-VEGF therapy, some patients do not respond or may respond suboptimally. In the case of refractory or rapidly recurring fluid in nAMD, clinicians may switch to another anti-VEGF agent. TITAN was an observational study that assessed the effectiveness and safety of intravitreal aflibercept (IVT-AFL) in patients with nAMD refractory to ranibizumab who switched to IVT-AFL after less than 12 months of ranibizumab treatment in routine clinical practice in France.MethodsTITAN was an observational, retrospective and prospective 12-month study conducted at 28 centres in France. Patients with nAMD refractory to ranibizumab were enrolled. Patients who were switched from ranibizumab to IVT-AFL were followed for 12 months. Data were obtained from medical records for retrospectively included patients, and at routine follow-up visits for those included prospectively. The main outcome measure was percentage of patients who achieved treatment success (gain of ≥1 Early Treatment Diabetic Retinopathy Study letters in best-corrected visual acuity [BCVA] and/or any reduction in central retinal thickness [CRT]) from baseline to 12 months after switching. A sample size of 225 patients was determined based on a 2-sided 95% confidence interval with a width equal to 0.12 when the sample proportion was 0.70.ResultsWe analysed safety data (N = 217) and clinical outcomes from patients in the per-protocol population (n = 125). The mean (standard deviation) number of IVT-AFL injections was 7.5 (2.6). Treatment success was achieved in 68.8% of patients. Mean BCVA change from baseline to Month 12 was + 1.5 letters (P = 0.105) and the mean CRT change was - 45.0 μm (P < 0.001). In a subgroup analysis, in patients who received three initial monthly IVT-AFL injections, mean BCVA gain was 3.3 letters at Month 12 (P = 0.015). Excluding lack of efficacy and inappropriate scheduling of drug administration, the most common adverse event was eye pain (2.3%).ConclusionsSwitching ranibizumab-refractory patients with nAMD to IVT-AFL may improve visual outcomes in some patients, particularly those who receive three initial monthly injections.Trial registrationClinicalTrials.gov , NCT02321241 . First posted: December 22, 2014; Last update posted: July 2, 2018.