scholarly journals Intraokulare Entzündungen bei Brolucizumab-Anwendung

2021 ◽  
Author(s):  
F. G. Holz ◽  
C. Heinz ◽  
A. Wolf ◽  
H. Hoerauf ◽  
U. Pleyer
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Review Committee ◽  
Oder Eine ◽  
Diagnostik Und Therapie ◽  
Factor Inhibitor ◽  
Antientzündliche Therapie ◽  
Endothelial Growth Factor

ZusammenfassungDer VEGF(„vascular endothelial growth factor“)-Inhibitor Brolucizumab ist seit Oktober 2019 in den USA und seit Februar 2020 in Europa zur Behandlung der neovaskulären altersabhängigen Makuladegeneration (nAMD) zugelassen. Grundlage der Zulassung bildeten die randomisierten, doppel-blinden Phase-III-Studien HAWK und HARRIER mit insgesamt 1817 Patienten. Hierbei zeigte Brolucizumab 6 mg (je nach Krankheitsaktivität alle 12 oder alle 8 Wochen verabreicht) eine nichtunterlegene Wirksamkeit in Bezug auf den bestkorrigierten Visus gegenüber Aflibercept 2 mg (alle 8 Wochen verabreicht). Erste Rückmeldungen zum Einsatz von Brolucizumab nach der Marktzulassung in den USA haben einzelne, z. T. schwerwiegende Fälle behandlungsassoziierter intraokularer Entzündungen mit retinaler Vaskulitis und/oder retinaler, vaskulärer Okklusion beschrieben, die teilweise zu einem schweren Visusverlust führten. Die Daten der Zulassungsstudien wurden daraufhin durch ein Safety Review Committee (SRC) unabhängig retrospektiv analysiert. Ziel der vorliegenden Publikation ist es, Anwendern eine Orientierungshilfe aus Autorensicht bei der Therapie einer Brolucizumab-assoziierten intraokularen Entzündung zu bieten. Von zentraler Bedeutung ist hierbei auch eine erweiterte Aufklärung der Patienten über Symptome einer intraokularen Entzündung. Obwohl die Fallserien und die HAWK/HARRIER-Daten es nicht abschließend beantworten, bleiben eine zu späte Detektion, eine unterdosierte antientzündliche Therapie oder eine unbedachte Wiederbehandlung mit Brolucizumab dem Verdacht ausgesetzt, Komplikationen zu verstärken. Ein Stopp der Brolucizumab-Therapie sollte grundsätzlich erfolgen, sobald es nach Gabe des Medikaments zu intraokularen Entzündungen mit oder ohne retinalen Vaskulitiden und oder Gefäßverschluss kam. Abhängig vom Schwerpunkt der Entzündung werden dem Behandler an die Leitlinien und Stellungnahmen angelehnte Empfehlungen für Diagnostik und Therapie dargestellt. Diese Übersichtsarbeit ersetzt nicht die fachgesellschaftlichen Stellungnahmen.

Fortgeschrittenes medulläres Schilddrüsenkarzinom: Vandetanib verbessert das progressionsfreie Überleben

2012 ◽  
Vol 03 (02) ◽  
pp. 93-92
Author(s):  
Alexander Kretzschmar
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Medulläres Schilddrüsenkarzinom ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Vandetanib ist ein oraler Hemmer des RET-Kinase-, VEGF (Vascular Endothelial Growth Factor Receptor)- und EGFR (Epidermal Growth Factor Receptor)-Signalwegs. In einer zulassungsrelevanten, randomisierten, doppelblinden, placebokontrollierten Phase- III-Studie verlängerte der Tyrosinkinasehemmer das progressionsfreie Überleben (PFS) signifikant länger als Placebo.

Treatment of Coates retinitis in both eyes in a 5-year-old girl

2021 ◽  
pp. 63-65
Author(s):  
A.O. Nazarenko ◽  
◽  
E.E. Sidorenko ◽  
I.V. Suhanova ◽  
A.R. Shavaleeva ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Retinal Detachment ◽  
Clinical Case ◽  
Vascular Endothelial ◽  
Vegf Inhibitor ◽  
Vascular Activity ◽  
Factor Inhibitor ◽  
The Right ◽  
Endothelial Growth Factor

Purpose. To present a rare clinical case of bilateral Coates retinitis in a 5-year-old girl. Material and methods. A clinical case of a 5-year-old girl with rare Coat's retinitis in both eyes is described. The disease occurred abruptly: the child's parents noted the appearance of leukocoria in the right eye. After the examination Coates ' retinitis was diagnosed. At the time of examination in the clinic, there was a retinal detachment in the right eye, the surgical treatment was performed: lensvitrshvartectomy, plastic surgery of the anterior chamber, with the melting of the retina with perfluoroorganic compounds, drainage of subretinalfluid, endolaser coagulation on the right eye. A month after the first symptoms appeared in the right eye, the patient complained of decreased vision in the left eye. Examination on the pediatric retinal camera showed an increase in vascular activity in the left eye, and signs of Coats' retinitis were revealed. Results. As a therapy for this disease, the patient was twice injected intravitreally inhibitor of vascular endothelial growth factor (VEGF inhibitor) into the left eye with positive dynamics noted as a decrease in the activity of retinal vessels and leveling of the exudative component, as well as with an increase in visual acuity in the left eye. Conclusion. This clinical case demonstrates that intravitreal administration of inhibitor VEGF with traditional methods of treatment can be used as a treatment for patients with Coates retinitis. Key words: Coat's retinitis, Coats' disease, vascular endothelial growth factor inhibitor, aflibercept, intravitreal injection, anti-VEGF, retinal detachment.

scholarly journals Predictive Impact of Circulating Vascular Endothelial Growth Factor in Four Phase III Trials Evaluating Bevacizumab

2012 ◽  
Vol 19 (4) ◽  
pp. 929-937 ◽  
Author(s):  
Priti S. Hegde ◽  
Adrian M. Jubb ◽  
Dafeng Chen ◽  
Nicole F. Li ◽  
Y. Gloria Meng ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Phase Iii Trials ◽  
Endothelial Growth Factor

T-cell receptor (TCR) repertoire in metastatic renal cell carcinoma (RCC) patients treated with first-line vascular endothelial growth factor receptor blockade.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 501-501
Author(s):  
Thai Huu Ho ◽  
Robert Charles Gagnon ◽  
Yuan Liu ◽  
F. Stephen Hodi ◽  
Sabina Signoretti ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
T Cell ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Treated Group ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Cell Repertoire ◽  
Endothelial Growth Factor

501 Background: Reports have demonstrated an inverse relationship between suppression of immune surveillance mechanisms and activation of the vascular endothelial growth factor receptor (VEGFR) pathway suggesting that T cell repertoires may impact response to VEGFR blockade. We evaluated the association between clinical outcomes and T cell repertoire in metastatic RCC patients receiving a front-line anti-VEGFR, pazopanib. Methods: Pre-treatment RCC tumors were analyzed from VEG105192, a phase III study of mRCC patients randomized (2:1) to pazopanib (paz) 800 mg daily vs placebo (pbo) for TCR gamma (TCRG) and TCR beta (TCRB) CDR3 regions. Using the Adaptive Biotechnologies immunoSEQ Assay, we assessed TCR clonality, a measure of total repertoire represented by expanded clones, and entropy, a measure of evenness and diversity. PD-L1 was evaluated by immunohistochemistry (IHC) H-Scores. The goal of the study was to determine if the repertoire of T cell clones was associated with progression-free survival as a clinical endpoint. Results: In the cohort with available tissue, the median PFS was 10.8 and 5.5 months (mos) for paz and pbo, respectively. TCRB (n = 114) and TCRG (n = 43 pbo, 109 paz) clonality ranged from 0-0.31 and 0-0.98, and entropy from 1-12.1 and 0-10.37, respectively. TCRB and TCRG entropy were highly correlated (Spearman’s R = 0.92, n = 114). Samples from the pbo-treated group with higher TCRG entropy, defined as the top 25th percentile, were associated with an improved median PFS (12.8 months) when compared to the lower 75th percentile (3.1 months, P = 0.023); similar trends were seen for TCRB entropy. Neither entropy nor clonality was associated with maximal reduction in tumor volume in the paz-treated group. PD-L1 H-scores were not associated with entropy or clonality (P > 0.05). Conclusions: Our data suggests that RCC samples with higher entropy are associated with a favorable prognosis. Identification of tumors with restricted TCRB/G chain usage and less diverse repertoire, as represented by lower entropy and higher clonality, may impact responses to VEGFR blockade and requires further study. Clinical trial information: NCT00334282.

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