Translated from
Rev Prescrire
October 2014; 34 (372): 739
aflibercept
(E
ylea
°)
and central retinal vein occlusion
No proven advantages but many uncertainties
Central retinal vein occlusion leads
to a loss of visual acuity, the severity of
which depends mainly on the ischaemic
nature of the occlusion and the pres-
ence of macular oedema, which some-
times resolves spontaneously. There is
no standard drug therapy.
The indications of aflibercept (Eylea°,
Bayer), a VEGF inhibitor, were extended
in the European Union to cover patients
with loss of visual acuity due to macular
oedema following central retinal vein
occlusion. Ranibizumab is also used in
this situation, albeit with an uncertain
harm-benefit balance.
Clinical evaluation of aflibercept is
based on two randomised, placebo-controlled trials in 366 patients, only
12% of whom had ischaemic occlusion.
The patients received either aflibercept
or sham injections every month for six
months, then at checking conducted
initially each month and subsequently
at longer intervals.
Combined analysis of the two trials
after the first six months of follow-up
showed that 60% of patients in the afli-
bercept group and 17% of those in the
control group had at least a 15-letter
improvement in visual acuity (primary
endpoint), a statistically significant dif-
ference. The gap between the groups
gradually narrowed over time, due to an
improvement in the control group.
The main adverse effects of afliber-
cept are potentially serious ocular disor-
ders due mainly to the intravitreal injec-
tion itself, namely eye pain, conjunctival
and retinal haemorrhage, intraocular
pressure elevation, cataracts, endoph-
thalmitis. Post-marketing surveillance
has identified several cases of generally
reversible blindness in patients treated
with aflibercept.
Aflibercept was teratogenic in experi-
mental animals, and women of child-
bearingagemustthereforeuseaneffective
contraceptive both during treatment and
for at least three months after the last
injection.
The packaging available in France
is poorly designed: a prefilled syringe
would be preferable, to ensure that the
precise required volume is injected.
In practice, patients with visual loss
due to macular oedema following cen-
tral retinal vein occlusion should first be
monitored to see whether or not their
condition improves spontaneously. The
optimal dose of aflibercept for patients
whose vision deteriorates has not been
established, and long-term efficacy
remains to be determined. There is
no evidence that aflibercept has any
advantages over ranibizumab in terms
of either efficacy or adverse effects.
©Prescrire
Prescrire Int • February 2015
aflibercept
solution for intravitreal injection
E
ylea
°
• 4 mg
of
aflibercept
in 0.1 ml
VEGF inhibitor
New indication:
“treatment of visual
impairment due to macular oedema
secondary to central-retinal-vein occlusion
(CRVO)”.
[EU marketing authorisation, centralised
procedure]
JUDGEMENT RESERVED
The optimal dosage of
aflibercept
for patients
with visual loss due
to macular oedema
secondary to central
retinal vein occlusion remains to
be determined. The long-term effi-
cacy of
aflibercept
in this setting
is not known, and adverse effects
are potentially severe. The overall
harm-benefit balance of
aflibercept
is uncertain and not clearly better
than that of
ranibizumab
.
Rev Prescrire
2014; 34 (372): 739.
In response to our request for infor-
mation Bayer Healthcare failed to
provide us with any documentation.
New Products
P
age
4
•Prescrire International Special Edition 2015/Volume 24 N°158
A
Abstract
P
rescrire
’
s
ratings
Our judgement is based on the therapeutic
advance of the new product.
It considers not only the inherent value of
each product in terms of its risk-benefit
balance, but also its advantages and
disadvantages relative to existing products
available in France. Note that the relative
value of new products can vary from one
country to another.
BRAVO:
The product is a major therapeu-
tic advance in an area where previously no
treatment was available.
A REAL ADVANCE:
The product is an impor-
tant therapeutic innovation but has certain
limitations.
OFFERS AN ADVANTAGE:
The product has
some value but does not fundamentally
change the present therapeutic practice.
POSSIBLY HELPFUL:
The product has mini-
mal additional value, and should not change
prescribing habits except in rare circums-
tances.
NOTHING NEW:
The product may be a new
substance but is superfluous because it does
not add to the clinical possibilities offered by
previous products available. In most cases it
concerns a me-too product.
JUDGEMENT RESERVED:
The editors post-
pone their rating until better data and a more
thorough evaluation of the drug are avai-
lable.
NOT
ACCEPTABLE:
Product
without evident benefit but with
potential or real disadvantages.
Quality of information from
pharmaceutical companies
In response to our systematic requests
Company provided detailed information
including unpublished data and packaging
items.
Company provided information limited to ad-
ministrative and published data.
Company provided minimal information, main-
ly administrative data.
Company provided no information.
