RESUMEN
PURPOSE: The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL]). METHOD: Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks. The primary endpoint was mean change in best-corrected visual acuity score from baseline to Week 8. Secondary endpoints included anatomical outcomes, best-corrected visual acuity at Weeks 24 and 52, safety, and pharmacokinetics. RESULTS: Similarity in mean change in best-corrected visual acuity score was established between SDZ-AFL (n = 235) and Ref-AFL (n = 226) at Week 8 (difference: -0.3 [90% CI, -1.5 to 1.0]) and Week 52. No clinically meaningful differences occurred between groups in anatomical outcomes. Safety profiles were similar, with comparable incidences of treatment-related adverse events (SDZ-AFL: 2.5%; Ref-AFL: 2.9%). The incidence of anti-drug antibodies was similar between groups. Systemic free aflibercept concentrations 24 hours postdose were low and comparable between SDZ-AFL and Ref-AFL. CONCLUSION: Proposed biosimilar aflibercept matched reference aflibercept in efficacy, safety, and pharmacokinetics in participants with neovascular age-related macular degeneration. Therefore, this Phase 3 study confirmed biosimilarity of SDZ-AFL to Ref-AFL.
Asunto(s)
Inhibidores de la Angiogénesis , Biosimilares Farmacéuticos , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Agudeza Visual , Degeneración Macular Húmeda , Humanos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Método Doble Ciego , Masculino , Femenino , Estudios Prospectivos , Anciano , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/farmacocinética , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/fisiopatología , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/farmacocinética , Anciano de 80 o más Años , Resultado del Tratamiento , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Estudios de Seguimiento , Factores de TiempoRESUMEN
OBJECTIVE: To assess the rate and risk factors for reactivation of retinopathy of prematurity (ROP) after intravitreal injection (IVI) of antivascular endothelial growth factor (VEGF) agents. STUDY DESIGN: Infants who received IVI therapy between 2017 and 2022 were enrolled and divided into 2 groups: those with and without ROP reactivation. Information on ROP variables and patient variables were analyzed using multivariable logistic regression. RESULTS: A total of 114 infants with 223 eyes were enrolled in the study. The ROP reactivation rate was 11.4% of infants (9.9% of eyes). The mean duration of reactivation was 84 ± 45 days. Among the 223 eyes treated with IVI, reactivation rates were 6% for bevacizumab, 13.9% for aflibercept, and 22.2% for ranibizumab. A multivariable regression model showed that ranibizumab was an independent risk factor (OR 11.4, P = .008) for reactivation. Other risk factors included infants with periventricular leukomalacia (OR 13.8, P = .003), patent ductus arteriosus ligation (OR 10.7, P = .032), and infants who still required invasive mechanical ventilation on the day of IVI therapy (OR 7.0, P = .018). CONCLUSIONS: All anti-VEGF agents carry a risk of ROP reactivation, with the risk being greater with ranibizumab 0.25 mg than with bevacizumab 0.625 mg. Reactivation of ROP should be assessed vigilantly, especially in those infants with increased risks. Future research to determine the optimal anti-VEGF selection and dosage in high-risk infants is warranted.
Asunto(s)
Inhibidores de la Angiogénesis , Bevacizumab , Inyecciones Intravítreas , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Retinopatía de la Prematuridad , Humanos , Retinopatía de la Prematuridad/tratamiento farmacológico , Inyecciones Intravítreas/efectos adversos , Masculino , Femenino , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/administración & dosificación , Recién Nacido , Bevacizumab/efectos adversos , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Factores de Riesgo , Ranibizumab/administración & dosificación , Ranibizumab/efectos adversos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Estudios Retrospectivos , Recurrencia , Recien Nacido Prematuro , LactanteRESUMEN
ABSTRACT Objective: To characterize the effectiveness of anti-vascular endothelial growth factor drugs in exudative age-related macular degeneration. Methods: Retrospective longitudinal study of 54 patients with age-related macular degeneration receiving bevacizumab or aflibercept. Demographic data, visual acuity, and central retinal thickness measurements were collected. Improvement/stability of visual acuity and reduction in retinal thickness configured satisfactory responses. Results: Among the 60 eyes studied, there was no difference (p = 0.262) in satisfactory response when using bevacizumab (48.5%) or aflibercept (63.0%). Snellen's visual acuity, letter gain, and retinal thickness showed improvement or maintenance in 55.0%, 32.8%, and 78.3% of cases, respectively. The percentage of improvement/maintenance was higher in eyes with an initial visual acuity of < Snellen 20/400 (70.0% versus 40.0%; p = 0.002). Conclusion: A higher percentage of improvement/stabilization of visual acuity and macular thickness was observed in patients with age-related macular degeneration, with better response in patients with visual acuity worse than Snellen 20/400.
RESUMO Objetivo: Caracterizar a efetividade de medicamentos antifactor de crescimento endotelial vascular na degeneração macular relacionada à idade exsudativa. Métodos: Estudo longitudinal retrospectivo em 54 pacientes com degeneração macular relacionada à idade que usaram bevacizumab ou aflibercept. Foram coletados dados demográficos, da acuidade visual e da espessura central da retina. Melhora/estabilidade da acuidade visual e redução da espessura configuraram respostas satisfatórias. Resultados: Entre 60 olhos estudados, não houve diferença (p = 0,262) de acordo com o uso de bevacizumab (48,5%) ou aflibercept (63,0%). Acuidade visual segundo Snellen, ganho de letras e espessura retiniana demonstraram melhora ou estabilidade em 55,0%, 32,8% e 78,3% dos casos, respectivamente. Entre os olhos com acuidade visual inicial < 20/400, o percentual de melhora/estabilidade foi superior (70,0% versus 40,0%; p = 0,002). Conclusão: Em pacientes com degeneração macular relacionada à idade, foi percebida uma maior proporção de melhora ou estabilização da acuidade visual e espessura macular, com melhor resposta entre os pacientes com visão pior que 20/400.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Degeneración Macular Húmeda/tratamiento farmacológico , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Agudeza Visual , Estudios Retrospectivos , Estudios de Cohortes , Estudios Longitudinales , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Tomografía de Coherencia Óptica , Degeneración Macular Húmeda/diagnóstico , Inyecciones Intravítreas , Degeneración Macular/diagnósticoRESUMEN
PURPOSE: To compare the efficacy of three initial monthly intravitreal aflibercept injections followed by pro re nata (3+PRN) dosing versus five initial monthly intravitreal aflibercept injections followed by pro re nata (5+PRN) dosing in patients with diabetic macular edema. METHODS: A total of 60 treatment-naïve patients with macular edema who underwent intravitreal aflibercept injections (2 mg/0.05 mL) with at least one year of follow-up were analyzed in this retrospective and comparative study. The patients were divided into two groups according to the number of intravitreal aflibercept injections administered in the loading phase. The 3+PRN group comprised 27 patients, whereas the 5+PRN group comprised 33 patients. The visual and anatomical outcomes were compared between the two groups at baseline and at 3, 6, 9, and 12 months. RESULTS: Both 3+PRN and 5+PRN, showed statistically significant improvements in the best-corrected visual acuity and central macular thicknesse throughout the study period (p<0.001 and, p<0.001, respectively). There were no significant differences between the two groups in terms of changes in the best-corrected visual acuity and central macular thickness (p=0.453 and, p=0.784, respectively). The mean number of intravitreal aflibercept injections was significantly greater in the 5+PRN group (6.1 ± 0.8) than in the 3+PRN group (3.9 ± 0.8) (p<0.001). CONCLUSION: The 3+PRN and 5+PRN regimens showed similar 12-month visual and anatomical outcomes following treatment with intravitreal aflibercept injections in patients with macular edema.
Asunto(s)
Inhibidores de la Angiogénesis , Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Inhibidores de la Angiogénesis/administración & dosificación , Retinopatía Diabética/complicaciones , Retinopatía Diabética/tratamiento farmacológico , Humanos , Inyecciones Intravítreas , Edema Macular/tratamiento farmacológico , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza VisualRESUMEN
ABSTRACT Purpose: To compare the efficacy of three initial monthly intravitreal aflibercept injections followed by pro re nata (3+PRN) dosing versus five initial monthly intravitreal aflibercept injections followed by pro re nata (5+PRN) dosing in patients with diabetic macular edema. Methods: A total of 60 treatment-naïve patients with macular edema who underwent intravitreal aflibercept injections (2 mg/0.05 mL) with at least one year of follow-up were analyzed in this retrospective and comparative study. The patients were divided into two groups according to the number of intravitreal aflibercept injections administered in the loading phase. The 3+PRN group comprised 27 patients, whereas the 5+PRN group comprised 33 patients. The visual and anatomical outcomes were compared between the two groups at baseline and at 3, 6, 9, and 12 months. Results: Both 3+PRN and 5+PRN, showed statistically significant improvements in the best-corrected visual acuity and central macular thicknesse throughout the study period (p<0.001 and, p<0.001, respectively). There were no significant differences between the two groups in terms of changes in the best-corrected visual acuity and central macular thickness (p=0.453 and, p=0.784, respectively). The mean number of intravitreal aflibercept injections was significantly greater in the 5+PRN group (6.1 ± 0.8) than in the 3+PRN group (3.9 ± 0.8) (p<0.001). Conclusion: The 3+PRN and 5+PRN regimens showed similar 12-month visual and anatomical outcomes following treatment with intravitreal aflibercept injections in patients with macular edema.
RESUMO Objetivo: Comparar a eficácia de três injeções intravítreas mensais iniciais de aflibercept, seguidas de dosagem de pro re nata (3+PRN) versus cinco injeções mensais iniciais intravítreas de aflibercept, seguidas de doses de pro re nata (5 + PRN) em pacientes com edema macular diabético. Métodos: Foram analisados neste estudo retrospectivo e comparativo 60 pacientes que não receberam tratamento prévio com edema macular e foram submetidos a injeções intravítreas de aflibercept (2 mg/0,05 mL) com pelo menos um ano de acompanhamento. Os pacientes foram divididos em dois grupos de acordo com o número de injeções intravítreas de aflibercept administradas na fase inicial. O grupo 3+PRN compreendeu 27 pacientes, enquanto o grupo 5+PRN compreendeu 33 pacientes. Os resultados visuais e anatômicos foram comparados entre os dois grupos no período inicial e aos 3, 6, 9 e 12 meses. Resultados: Tanto os grupos 3+PRN quanto 5+PRN mostraram melhoras estatisticamente significativas na acuidade visual melhor corrigida e na espessura macular central ao longo do período de estudo (p<0,001 e p <0,001, respectivamente). Não houve diferenças significativas entre os dois grupos em termos de alterações na acuidade visual melhor corrigida e na espessura macular central (p=0,453 e p=0,784, respectivamente). O número médio de injeções intravítreas de aflibercept foi significativamente maior no grupo 5+PRN (6,1 ± 0,8) do que no grupo 3+PRN (3,9 ± 0,8) (p <0,001). Conclusão: Os regimes 3+PRN e 5+PRN mostraram resultados visuais e anatômicos semelhantes em 12 meses após o tratamento com injeções intravítreas de aflibercept em pacientes com edema macular.
Asunto(s)
Humanos , Proteínas Recombinantes de Fusión , Edema Macular , Inhibidores de la Angiogénesis , Receptores de Factores de Crecimiento Endotelial Vascular , Diabetes Mellitus , Retinopatía Diabética , Proteínas Recombinantes de Fusión/administración & dosificación , Agudeza Visual , Edema Macular/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Inhibidores de la Angiogénesis/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Retinopatía Diabética/complicaciones , Retinopatía Diabética/tratamiento farmacológico , Inyecciones Intravítreas , Ranibizumab/uso terapéuticoRESUMEN
PURPOSE: To determine the effect achieved from a single dose of anti-VEGF treatment switch, in patients with nAMD previously treated with bevacizumab, switched to either aflibercept or ranibizumab, and to compare the response between aflibercept and ranibizumab. METHODS: In retrospective, observational, and comparative study, patients were divided into two groups: Group 1, patients switched to aflibercept; Group 2, patients switched to ranibizumab. Paired samples t test was performed to measure differences in central macular thickness (CMT). To compare whether there were differences between groups mixed-design ANOVA was used. RESULTS: In Group 1, CMT changed from 360.51 to 260.16 µm, presenting a significant mean difference from PreSwitch to PostSwitch of 100.34 µm (p = 0.002, paired samples t test). In Group 2, CMT changed from 366.33 to 260.72 µm, showing a significant difference from PreSwitch to PostSwitch of 105.61 µm (p ≤ 0.000, paired samples t test). The mixed-design ANOVA compared both groups and resulted in a nonsignificant value of 0.90. CONCLUSION: The effect achieved from a single dose in patients switched to aflibercept or ranibizumab reduced significantly CMT measurements. Comparing aflibercept and ranibizumab, the effect appears to be similar in both drugs, in terms of reduction of CMT.
Asunto(s)
Mácula Lútea/patología , Ranibizumab/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Tomografía de Coherencia Óptica/métodos , Degeneración Macular Húmeda/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Relación Dosis-Respuesta a Droga , Sustitución de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Estudios Retrospectivos , Resultado del Tratamiento , Degeneración Macular Húmeda/diagnósticoRESUMEN
INTRODUCTION: Macular edema is a frequent complication of central retinal vein occlusion that might lead to deterioration of visual acuity. The most commonly used treatments are dexamethasone implant and anti-vascular endothelial growth factor drugs, being aflibercept one of the most commonly used them. However, there is no consensus about which treatment constitute the best alternative. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified two systematic reviews that included four primary studies overall, all randomized trials. We concluded that it is not possible to establish whether aflibercept is superior to dexamethasone in terms of improvement of visual acuity and safety, because the certainty of the existing evidence has been evaluated as very low.
INTRODUCCIÓN: El edema macular es una complicación frecuente de la oclusión de la vena central de la retina que clínicamente provoca deterioro de la agudeza visual. Los tratamientos más utilizados son el implante de dexametasona y los fármacos anti factor del crecimiento endotelial vascular, destacando aflibercept dentro de estos. Sin embargo, no existe consenso acerca de qué tratamiento constituye la mejor alternativa. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos dos revisiones sistemáticas que en conjunto incluyeron cuatro estudios primarios, todos ensayos aleatorizados. Concluimos que no es posible establecer si aflibercept es superior a dexametasona en términos de mejora de agudeza visual y seguridad, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.
Asunto(s)
Dexametasona/administración & dosificación , Edema Macular/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Inhibidores de la Angiogénesis/administración & dosificación , Antiinflamatorios/administración & dosificación , Bases de Datos Factuales , Humanos , Edema Macular/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Oclusión de la Vena Retiniana/complicacionesRESUMEN
INTRODUCCIÓN El edema macular es una complicación frecuente de la oclusión de la vena central de la retina que clínicamente provoca deterioro de la agudeza visual. Los tratamientos más utilizados son el implante de dexametasona y los fármacos anti factor del crecimiento endotelial vascular, destacando aflibercept dentro de estos. Sin embargo, no existe consenso acerca de qué tratamiento constituye la mejor alternativa. MÉTODOS Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos dos revisiones sistemáticas que en conjunto incluyeron cuatro estudios primarios, todos ensayos aleatorizados. Concluimos que no es posible establecer si aflibercept es superior a dexametasona en términos de mejora de agudeza visual y seguridad, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.
INTRODUCTION Macular edema is a frequent complication of central retinal vein occlusion that might lead to deterioration of visual acuity. The most commonly used treatments are dexamethasone implant and anti-vascular endothelial growth factor drugs, being aflibercept one of the most commonly used them. However, there is no consensus about which treatment constitute the best alternative. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified two systematic reviews that included four primary studies overall, all randomized trials. We concluded that it is not possible to establish whether aflibercept is superior to dexamethasone in terms of improvement of visual acuity and safety, because the certainty of the existing evidence has been evaluated as very low.
Asunto(s)
Humanos , Proteínas Recombinantes de Fusión/administración & dosificación , Dexametasona/administración & dosificación , Edema Macular/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Oclusión de la Vena Retiniana/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Edema Macular/etiología , Bases de Datos Factuales , Inhibidores de la Angiogénesis/administración & dosificación , Antiinflamatorios/administración & dosificaciónRESUMEN
PURPOSE: To describe the visual, tomographic, and electroretinographic findings in a patient with macular edema secondary to branch retinal vein occlusion who was submitted to three consecutive intravitreal injections of ziv-aflibercept. METHODS: The patient underwent a complete ophthalmic examination, as well as optical coherence tomography and full-field electroretinography at baseline and 90 days after the first injection. RESULTS: The best-corrected visual acuity improved from 20/400 to 20/40, and the central retinal thickness decreased from 791 µm to 198 µm after three consecutive intravitreal injections of ziv-aflibercept. Full-field electroretinography showed an increase in cone amplitude and decrease in rod amplitude. No adverse side effects were observed after injections. CONCLUSION: Intravitreal injections of ziv-aflibercept showed both effectiveness and safety in the treatment of a patient with macular edema secondary to branch retinal vein occlusion. The observed anatomic (by ophthalmic examination, optical coherence tomography) and functional (best-corrected visual acuity, full-field electroretinography) improvements and lack of serious adverse side effects demonstrates the potential of intravitreal injections of ziv-aflibercept for the treatment of macular edema secondary to branch retinal vein occlusion.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Edema Macular/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Oclusión de la Vena Retiniana/complicaciones , Humanos , Inyecciones Intravítreas , Edema Macular/etiología , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
PURPOSE: To investigate the effect of vitreomacular adhesion (VMA) on the outcome of antiangiogenic treatment for neovascular age-related macular degeneration (AMD). METHODS: Ninety-nine eyes of 83 patients were used in our cohort study. We prospectively evaluated best corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients with neovascular AMD at baseline and 1, 2, 3, 6, and 12 months after treatment with anti-vascular endothelial growth factor (anti-VEGF) agents. All patients were stratified by spectral domain optical coherence tomography into 2 groups (i.e., VMA[+] and VMA[-]) according to the presence or absence of VMA, and the response to treatment was evaluated. RESULTS: Fifty-four eyes (54.5%) were included in the VMA(-) group and 45 eyes (45.5%) comprised the VMA(+) group. In paired comparisons of mean BCVA between baseline and each follow-up visit (1, 2, 3, 6, and 12 months), the VMA(-) group showed statistically significant improvement at 1, 2, and 3 months compared to baseline, and BCVA significantly improved only at 3 months in the VMA(+) group. For both groups, paired comparisons of CRT showed a statistically significant decrease when data obtained at 1, 2, 3, 6, and 12 months were compared to baseline values (p < 0.05). CONCLUSIONS: Posterior VMA is associated with a worse short-term outcome in patients with neovascular AMD treated with anti-VEGF agents.
Asunto(s)
Bevacizumab/administración & dosificación , Mácula Lútea/patología , Ranibizumab/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Cuerpo Vítreo/patología , Degeneración Macular Húmeda/tratamiento farmacológico , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Tiempo , Adherencias Tisulares/complicaciones , Adherencias Tisulares/diagnóstico , Tomografía de Coherencia Óptica , Agudeza Visual , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/etiologíaRESUMEN
PURPOSE: In the VELOUR study, aflibercept + FOLFIRI regimen resulted in improved survival in metastatic colorectal cancer (mCRC) patients who progressed after oxaliplatin. The use of aflibercept outside the clinical trial framework needs to be further assessed in terms of effectiveness and tolerability. METHODS: Early access to aflibercept through a named patient programme (NPP) was provided to mCRC patients receiving FOLFIRI as second-line treatment in Spain. The effectiveness of aflibercept was assessed as progression-free survival (PFS) achieved within the NPP population. Post hoc analyses on PFS were done according to certain baseline characteristics (K-RAS mutation, prior targeted therapy) or prognostic factors. RESULTS: Registries from 71 mCRC patients included in the NPP were reviewed retrospectively. The median age for the NPP population was 64 years (19.7 % aged ≥70 years) and 63.4 % patients had ≥2 metastases. A median PFS of 5.3 months (95 % CI, 3.6-8.5 months) was achieved, which did not depend on K-RAS mutation status or prior targeted therapy received. The risk of progression or death increased in patients with a poor prognosis as per the GERCOR score (performance status [PS] 1-2 and increased baseline lactate dehydrogenase [LDH] level) compared with patients with a good prognosis (PS 0 and normal LDH level) (median PFS: 2.6 vs. 8.3 months, respectively; p = 0.0124). Aflibercept was well tolerated, with a manageable toxicity profile. CONCLUSIONS: Bearing in mind the differences in sample size, the PFS achieved with the aflibercept + FOLFIRI regimen in the real-life practice setting is comparable to that observed in the clinical trial setting.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Irinotecán , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Peritoneales/secundario , Pronóstico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Estudios Retrospectivos , España , Tasa de SupervivenciaRESUMEN
PURPOSE: To evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration. METHODS: Fifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment. RESULTS: Between baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P < 0.0001) from 9.51 ± 1.36 mm to 8.08 ± 1.34 mm, and the a-wave implicit time increased, with no differences in the other full-field electroretinography parameters. The average multifocal electroretinography macular responses within the first central 15° showed significantly (P < 0.05) increased P1 amplitudes at 26 weeks. No systemic or ocular complications developed. CONCLUSION: Intravitreal ziv-aflibercept significantly improved the best-corrected visual acuity, multifocal electroretinography amplitudes, central retinal thickness, and total macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.
Asunto(s)
Electrorretinografía/métodos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Retina/fisiopatología , Agudeza Visual , Degeneración Macular Húmeda/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Retina/diagnóstico por imagen , Retina/efectos de los fármacos , Factores de Tiempo , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/fisiopatologíaRESUMEN
PURPOSE: The aim of this study was to access the safety profiles of 2 fusion proteins with anti-vascular endothelial growth factor action (ziv-aflibercept and aflibercept) on retinal pigment epithelium cells and Muller-Glia cells in culture by assessing cell viability post drug exposure. METHODS: Primary human retinal pigment epithelium cells (pRPE) and Muller-Glia cells (Mio-M1) were exposed to the clinical standardized concentrations of ziv-aflibercept (25 mg/mL) and aflibercept (40 mg/mL). Progressively higher concentrations of NaCl (300, 500, 1,000, 1,500, 2,000, 5,000, and 10,000 mosm/kg) were also applied to cells to assess the possibility of potentiating hyperosmotic cytotoxity effect. The study was applied to measure pRPE and Mio-M1 viability by a tetrazolium dye-reduction assay (XTT). RESULTS: Cell viability of both pRPE and Mio-M1 presented no significant changes after exposure of ziv-aflibercept and aflibercept. Progressive NaCl concentrations did not significantly alter cell viability. The exposure to the negative control of 75 µL/mL of dimethyl sulfoxide showed significant reduction in cell viability. CONCLUSIONS: At clinical doses, neither ziv-aflibercept nor aflibercept caused any significant reduction in cell viability in vitro. Furthermore, injection solutions of NaCl with higher osmolality caused no significant reduction in cell viability.
Asunto(s)
Células Ependimogliales/patología , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Epitelio Pigmentado de la Retina/patología , Cadáver , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Ependimogliales/efectos de los fármacos , Humanos , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Epitelio Pigmentado de la Retina/efectos de los fármacosRESUMEN
ABSTRACT Purpose: The present study compared the efficacy of aflibercept for neovascular age-related macular degeneration (NV-AMD) in patients with complete ranibizumab resistance and tachyphylaxis. Methods: Forty-four eyes of 38 neovascular age-related macular degeneration patients were evaluated. Eyes were divided into a complete resistance group (n=23 eyes) and tachyphylaxis group (n=21 eyes). Results: After three injections, eight (38.1%) patients in the tachyphylaxis group and nine (39.1%) in the complete resistance group presented with macular dryness. After the first injection of aflibercept, the mean visual acuity improved significantly in the tachyphylaxis group (p=0.018) but remained unchanged in the complete resistance group (p=0.37). There was a non-significant trend towards improved mean visual acuity in both groups after the second and third injections relative to the acuity at the final visit for ranibizumab treatment. In the tachyphylaxis group, the presence of subfoveal pigmented epithelium detachment (PED) decreased significantly after intravitreal aflibercept treatment. Conclusions: Although treatment with aflibercept yielded generally positive anatomical results in both groups, no significant increase in visual acuity was achieved.
RESUMO Objetivo: O presente estudo comparou a eficácia do aflibercept na degeneração macular neovascular relacionada à idade (NV-AMD) com de resistência completa ao ranibizumab e taquifilaxia ao ranibizumab. Método: Quarenta e quatro olhos de 38 pacientes com degeneração macular neovascular relacionada à idade foram inscritos. Eles foram divididos em dois grupos: grupo de resistência completa (n=23 olhos) e grupo taquifilaxia (n=21 olhos). Resultados: Depois de três injeções, 8 (38,1%) olhos no grupo de taquifilaxia e 9 (39,1%) olhos no grupo de resistência completa, apresentaram mácula seca. Após a primeira injeção de aflibercept, a acuidade visual média melhorou significativamente no grupo taquifilaxia (p=0,018) e manteve-se inalterada no grupo de resistência completa (p=0,37). Houve uma tendência de melhora da acuidade visual média em ambos os grupos após a segunda e terceira injeções em comparação com a última visita do tratamento com ranibizumab, mas isso não foi estatisticamente significativo. A presença de descolamento do epitélio pimentado subfoveal (PED) em olhos com taquifilaxia ao ranibizumab diminuiu significativamente após o tratamento aflibercept intravítreo. Conclusões: Embora o tratamento com aflibercept tenha mostrado resultados anatômicos positivas em ambos os grupos, não foi obtida melhora significativa da acuidade visual.
Asunto(s)
Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Taquifilaxis , Proteínas Recombinantes de Fusión/uso terapéutico , Agudeza Visual/efectos de los fármacos , Inhibidores de la Angiogénesis/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Ranibizumab/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Proteínas Recombinantes de Fusión/administración & dosificación , Desprendimiento de Retina/etiología , Desprendimiento de Retina/tratamiento farmacológico , Resistencia a Medicamentos , Resultado del Tratamiento , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Epitelio Pigmentado de la Retina/efectos de los fármacos , Inyecciones Intravítreas , Degeneración Macular/complicacionesRESUMEN
PURPOSE:: The present study compared the efficacy of aflibercept for neovascular age-related macular degeneration (NV-AMD) in patients with complete ranibizumab resistance and tachyphylaxis. METHODS:: Forty-four eyes of 38 neovascular age-related macular degeneration patients were evaluated. Eyes were divided into a complete resistance group (n=23 eyes) and tachyphylaxis group (n=21 eyes). RESULTS:: After three injections, eight (38.1%) patients in the tachyphylaxis group and nine (39.1%) in the complete resistance group presented with macular dryness. After the first injection of aflibercept, the mean visual acuity improved significantly in the tachyphylaxis group (p=0.018) but remained unchanged in the complete resistance group (p=0.37). There was a non-significant trend towards improved mean visual acuity in both groups after the second and third injections relative to the acuity at the final visit for ranibizumab treatment. In the tachyphylaxis group, the presence of subfoveal pigmented epithelium detachment (PED) decreased significantly after intravitreal aflibercept treatment. CONCLUSIONS:: Although treatment with aflibercept yielded generally positive anatomical results in both groups, no significant increase in visual acuity was achieved.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Taquifilaxis , Agudeza Visual/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Resistencia a Medicamentos , Humanos , Inyecciones Intravítreas , Degeneración Macular/complicaciones , Persona de Mediana Edad , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Desprendimiento de Retina/tratamiento farmacológico , Desprendimiento de Retina/etiología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Líquido Subretiniano/metabolismo , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
BACKGROUND: Docetaxel plus prednisone is standard first-line chemotherapy for men with metastatic castrate-resistant prostate cancer. Aflibercept is a recombinant human fusion protein that binds A and B isoforms of VEGF and placental growth factor, thereby inhibiting angiogenesis. We assessed whether the addition of aflibercept to docetaxel and prednisone would improve overall survival in men with metastatic castrate-resistant prostate cancer compared with the addition of placebo to docetaxel and prednisone. METHODS: VENICE was a phase 3, multicentre, randomised double-blind placebo-controlled parallel group study done in 31 countries (187 sites). Men with metastatic castrate-resistant prostate cancer, adequate organ function, and no prior chemotherapy were treated with docetaxel (75 mg/m(2) intravenously every 3 weeks) and oral prednisone (5 mg twice daily) and randomly allocated (1:1) to receive aflibercept (6 mg/kg) or placebo, intravenously, every 3 weeks. Treatment allocation was done centrally via an interactive voice response system, using a computer-generated sequence with a permuted-block size of four and stratified according Eastern Co-operative Group performance status (0-1 vs 2). Patients, investigators, and other individuals responsible for study conduct and data analysis were masked to treatment assignment. Aflibercept or placebo vials were supplied in identical boxes. The primary endpoint was overall survival using intention-to-treat analysis. This is the primary analysis of the completed trial. The study is registered with ClinicalTrials.gov, number NCT00519285 FINDINGS: Between Aug 17, 2007, and Feb 11, 2010, 1224 men were randomly allocated to treatment: 612 to each group. At final analysis, median follow-up was 35 months (IQR 29-41) and 873 men had died. Median overall survival was 22·1 months (95·6% CI 20·3-24·1) in the aflibercept group and 21·2 months (19·6-23·8) in the placebo group (stratified hazard ratio 0·94, 95·6% CI 0·82-1·08; p=0·38). We recorded a higher incidence of grade 3-4 gastrointestinal disorders (182 [30%] vs 48 [8·0%]), haemorrhagic events (32 [5·2%] vs ten [1·7%]), hypertension (81 [13%] vs 20 [3·3%]), fatigue (97 [16%] vs 46 [7·7%]), infections (123 [20%] vs 60 [10%]) and treatment-related fatal adverse events (21 [3·4%] vs nine [1·5%]) in the aflibercept group than in the placebo group. INTERPRETATION: Aflibercept in combination with docetaxel and prednisone given as first-line chemotherapy for men with metastatic castrate-resistant prostate cancer resulted in no improvement in overall survival and added toxicity compared with placebo. Docetaxel plus prednisone remains the standard treatment for such men who need first-line chemotherapy. FUNDING: Sanofi and Regeneron Pharmaceuticals Inc.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Orquiectomía , Neoplasias de la Próstata/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Docetaxel , Método Doble Ciego , Esquema de Medicación , Resistencia a Antineoplásicos , Europa (Continente) , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , América del Norte , Prednisona/administración & dosificación , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/secundario , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , América del Sur , Taxoides/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the effects of local inhibition of vascular endothelial growth factor A (VEGFA) on proliferation and apoptosis of follicular cells in rat ovaries. To analyze the role of the PI3K/AKT signaling pathway on VEGFA effects. DESIGN: Experimental study. SETTING: Research laboratory. ANIMAL(S): Female Sprague Dawley rats, 21 days old, treated with equine chorionic gonadotropin (eCG). MAIN OUTCOME MEASURE(S): Follicular cell proliferation, apoptosis, and activation of the PI3K/AKT signaling pathway after intrabursal injection of a VEGFA inhibitor. RESULT(S): Inhibition of VEGFA leads to a decrease in the expression of the proliferation marker proliferating cell nuclear antigen (PCNA) in theca and granulosa cells (GC) and an increase in the activation of caspase 3 in antral follicles. Furthermore, we observed a decrease in the phosphorylation of RAC-alpha serine/threonine-protein kinase (AKT) and its target Bcl2 antagonist of cell death (BAD). No differences were found in the levels of kinase insert domain receptor (KDR) protein or in endothelial cell density. CONCLUSION(S): The VEGFA prevents apoptosis and stimulates proliferation of follicular cells, regulating follicular growth and development. The PI3K/AKT signaling pathway is one of the pathways involved in this mechanism. Therefore, VEGFA has a role as an antiapoptotic and proliferative factor in follicular cells from the rat ovary.