Final 4-year results of the RAINBOW real-world study: intravitreal aflibercept dosing regimens in France in treatment-naïve patients with neovascular age-related macular degeneration.

PURPOSE: The 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. METHODS: RAINBOW (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. RESULTS: Overall, 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. CONCLUSION: In 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 NUMBER: ClinicalTrials.gov Identifier: NCT02279537.

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

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.

Betabloqueantes en el tratamiento de la insuficiencia cardiaca estable en atención primaria / Beta-blocker treatment of stable heart failure in primary care

Introducción y objetivos. El objetivo es valorar la factibilidad y la tolerabilidad de la titulación de betabloqueantes en insuficiencia cardiaca sistólica en atención primaria. Métodos. Estudio de intervención antes/después. El estudio se realizó en dos centros de atención primaria de Barcelona. Se incluyó mediante muestreo sucesivo, desde abril de 2004 hasta abril de 2006, a los pacientes con IC sistólica sin tratamiento betabloqueante previo. Se inició titulación con bisoprolol o carvedilol a dosis mínima, doblándose cada 2 semanas en ausencia de contraindicaciones. Seguimiento durante 6 meses. Resultados. Se incluyó a un total de 88 pacientes (76,1% hombres, 23,9% mujeres. Edad media, 64,88 años). Al 57,1% se pautó bisoprolol y al 42,9%, carvedilol. El 75% alcanzaron la dosis diana, el 21,7% toleraron dosis menores de la diana y en el 3,3% hubo de retirarse el betabloqueante (1,1% bradicardia, 1,1% síncope, 1,1% accidente cerebrovascular). El 70,4% de los pacientes presentaron acontecimientos adversos. La mayoría de éstos (57,95%) se resolvieron sin cambios en el tratamiento. Los más frecuentes fueron: mareo (42,04%), astenia (35,22%) y el aumento de la disnea (17,04%). Hubo una mejora significativa de la clase funcional y de la fracción de eyección. Conclusiones. La mayoría de los acontecimientos adversos son leves. Las retiradas del tratamiento son escasas y la mayoría de los pacientes alcanzaron la dosis diana recomendada. Los médicos de atención primaria convenientemente formados pueden titular con seguridad los BB (AU)

Introduction and objectives. Beta-blocker treatment of stable heart failure in primary care. The objective was to evaluate the feasibility and tolerability of uptitrating beta-blockers in patients with stable systolic heart failure seen in primary care. Methods. Before and after intervention study. The study was conducted in two primary care centers in Barcelona, Spain. Consecutive samples of patients with systolic heart failure who had not received previous beta-blocker treatment were recruited between April 2004 and April 2006. Treatment was started with the lowest dose of bisoprolol or carvedilol and the dose was doubled every two weeks in the absence of contraindications. Patients were followed up for 6 months. Results. The study included 88 patients (76.1% male, 23,9% female, mean age 64.88 years). Of these, 57.1% were treated with bisoprolol and 42.9% with carvedilol. Overall, 75.0% reached the target dose, 21.7% tolerated a dose lower than the target dose, and 3.3% had the beta-blocker withdrawn (due to bradycardia in 1.1%, syncope in 1.1%, and stroke in 1.1%). Adverse events were experienced by 70.4%, the majority of which (57.95%) were resolved without changing treatment. The most common were nausea (42.04%), asthenia (35.22%), and increased dyspnea (17.04%). There were significant improvements in functional class and ejection fraction. Conclusions. The majority of adverse events were mild. Treatment was withdrawn in only a few patients and most reached the recommended target dose. Appropriately trained primary care physicians can uptitrate beta-blockers in heart failure patients without undue concern (AU)