PMID- 32454495
OWN - NLM
STAT- MEDLINE
DCOM- 20210830
LR  - 20210830
IS  - 1423-0267 (Electronic)
IS  - 0030-3755 (Linking)
VI  - 243
IP  - 6
DP  - 2020
TI  - Relationship between Aflibercept Efficacy and Genetic Variants of Genes 
      Associated with Neovascular Age-Related Macular Degeneration: The BIOIMAGE Trial.
PG  - 461-470
LID - 10.1159/000508902 [doi]
AB  - PURPOSE: To identify the genetic variants of the vascular endothelial growth 
      factor (VEGF) pathway genes and other genes associated with neovascular 
      age-related macular degeneration (nAMD) as possible predictive biomarkers of a 
      favorable treatment response to aflibercept. DESIGN: A 52-week (with extension 
      phase: 104-week), prospective, open-label, single-arm, multicenter, phase IV 
      trial was conducted in Spain. PARTICIPANTS: Patients with nAMD were enrolled. 
      METHODS: Aflibercept was administered every 8 weeks until week 48 (after 
      1-monthly loading doses over 3 months). After week 48, the interval between 
      visits for aflibercept administration was extended by 2 weeks per visit to a 
      maximum of 12 weeks if no evidence of disease activity was observed. A total of 
      338 SNPs in 90 genes associated with nAMD were analyzed. MAIN OUTCOME MEASURES: 
      Efficacy was evaluated mainly with best-corrected visual acuity (BCVA), and 
      adverse events (AEs) were reported. Treatment efficacy was defined as an increase 
      in BCVA >/=15 letters versus the baseline visit. Univariate and multivariate 
      logistic regressions were used to associate single-nucleotide polymorphisms 
      (SNPs) and treatment efficacy. RESULTS: 194 nonconsecutive patients were 
      enrolled, 170 completed the 52-week follow-up, and of the 85 patients who started 
      the extension phase, 77 completed this phase. Mean BCVA increased from baseline 
      to weeks 52 and 104 by 9 and 10 letters (p = 0.0001 for both), respectively. The 
      percentages of patients gaining >/=15 letters in weeks 52 and 104 were 33 and 31%, 
      respectively. Multivariate logistic regression showed significant associations of 
      6 SNPs (in 6 genes) with treatment efficacy: rs12366035 (VEGFB; TT; odds ratio 
      [OR] 217), rs25681 (C5; AA/AG; OR 19.7/8.3), rs17793056 (CX3CR1; CT/CC; OR 
      8.1/6.2), rs1800775 (CETP; CC; OR 6.6), rs2069845 (IL6; GG/AA; OR 5.6/3.3), and 
      rs13900 (CCL2; CT; OR 4.0). One percent of the patients reported 
      arteriothrombolic events related to aflibercept (cerebrovascular accident) 
      according to the Antiplatelet Trialist Collaboration, and 2% reported serious 
      ocular (retinal pigment epithelial tear, retinal tear, and endophthalmitis) and 
      systemic (cardiac failure, hypersensitivity, and transient ischemic attack) AEs 
      related to aflibercept. CONCLUSIONS: Results suggest strong pharmacogenetic 
      associations between one genetic variant of VEGFB (TT, rs12366035) and C5 (AA, 
      rs12366035) genes and the BCVA response after 52-week aflibercept treatment in 
      patients with nAMD. Likewise, the results support the efficacy of aflibercept 
      observed in phase III studies and a good safety profile.
CI  - (c) 2020 S. Karger AG, Basel.
FAU - Bures Jelstrup, Anniken
AU  - Bures Jelstrup A
AD  - Medical Retina Department, Instituto de Microcirugia Ocular, Fundacio de Recerca 
      de l'Institut de Microcirurgia Ocular, Barcelona, Spain.
FAU - Pomares, Esther
AU  - Pomares E
AD  - Genetics Department, Instituto de Microcirugia Ocular, Fundacio de Recerca de 
      l'Institut de Microcirurgia Ocular, Barcelona, Spain.
FAU - Navarro, Rafael
AU  - Navarro R
AD  - Medical Retina Department, Instituto de Microcirugia Ocular, Fundacio de Recerca 
      de l'Institut de Microcirurgia Ocular, Barcelona, Spain, navarro@imo.es.
CN  - on behalf of the BIOIMAGE Study Group
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20200526
PL  - Switzerland
TA  - Ophthalmologica
JT  - Ophthalmologica. Journal international d'ophtalmologie. International journal of 
      ophthalmology. Zeitschrift fur Augenheilkunde
JID - 0054655
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 15C2VL427D (aflibercept)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
SB  - IM
MH  - *Angiogenesis Inhibitors/therapeutic use
MH  - *Genetic Variation
MH  - Humans
MH  - Intravitreal Injections
MH  - *Macular Degeneration/drug therapy/genetics
MH  - Prospective Studies
MH  - *Receptors, Vascular Endothelial Growth Factor/therapeutic use
MH  - *Recombinant Fusion Proteins/therapeutic use
MH  - Spain
MH  - Treatment Outcome
MH  - *Vascular Endothelial Growth Factor A
MH  - Visual Acuity
OTO - NOTNLM
OT  - Aflibercept
OT  - Neovascular age-related macular degeneration
OT  - VEGF pathway
OT  - Vascular endothelial growth factor
EDAT- 2020/05/27 06:00
MHDA- 2021/08/31 06:00
CRDT- 2020/05/27 06:00
PHST- 2020/02/19 00:00 [received]
PHST- 2020/05/15 00:00 [accepted]
PHST- 2020/05/27 06:00 [pubmed]
PHST- 2021/08/31 06:00 [medline]
PHST- 2020/05/27 06:00 [entrez]
AID - 000508902 [pii]
AID - 10.1159/000508902 [doi]
PST - ppublish
SO  - Ophthalmologica. 2020;243(6):461-470. doi: 10.1159/000508902. Epub 2020 May 26.