Arch
Bronconeumol.
2017;
53(5)
:233–234
www.archbronconeumol.org
Editorial
Emerging
Therapies
in
Severe
Eosinophilic
Asthma
Nuevas
terapias
para
el
asma
eosinofílica
grave
Pee
Hwee
Pang
a
,
Christopher
E.
Brightling
b
,
∗
a
Department
of
Respiratory
and
Critical
Care
Medicine,
Tan
Tock
Seng
Hospital,
Singapore
b
Institute
for
Lung
Health,
NIHR
Respiratory
Biomedical
Research
Unit,
Department
of
Infection,
Immunity
&
Inflammation,
University
of
Leicester
and
University
Hospitals
of
Leicester
NHS
Trust,
Leicester,
UK
Asthma
is
a
complex,
heterogeneous
disease
characterized
by
chronic
airway
inflammation,
episodic
respiratory
symptoms,
and
associated
with
variable
expiratory
airflow
limitation.
The
preva-
lence
of
asthma
is
increasing,
and
is
estimated
to
affect
358
million
people
worldwide
in
the
recent
Global
Burden
of
Disease
report.
1
5%–10%
are
said
to
have
severe
asthma,
defined
as
asthma
that
requires
treatment
with
high
dose
inhaled
corticosteroids
and
a
second
controller
for
the
previous
year,
and/or
systemic
cortico-
steroids
for
≥
50%
of
the
previous
year
to
prevent
it
from
becoming
uncontrolled
or
that
remains
uncontrolled
despite
this
therapy.
2
This
subset
of
patients
has
poorer
lung
function,
quality
of
life,
and
recurrent
exacerbations;
is
at
increased
risk
of
significant
morbid-
ity
and
mortality,
and
exerts
a
substantial
burden
on
healthcare
resources.
Understanding
the
heterogeneity
of
the
airway
inflammation
in
severe
asthma
is
of
particular
importance
to
predict
future
risk
of
exacerbations
and
response
to
therapy.
The
presence
of
eosinophilic
airway
inflammation
is
associated
with
poorer
asthma
control
and
increased
risk
of
exacerbations,
3
and
is
a
good
predictor
of
a
favorable
response
to
corticosteroids.
4
Beyond
corticoste-
roids,
monoclonal
antibodies
targeting
Type
2
(T2)
immunity
and
consequent
eosinophilic
inflammation
in
severe
asthma
has
been
developed.
The
first
monoclonal
antibody
for
asthma
was
omalizumab,
a
humanized
monoclonal
antibody
against
IgE
used
since
2003
in
adults,
adolescents
and
children
over
6
years
of
age
with
moderate
to
severe
persistent
allergic
asthma
inadequately
con-
trolled
with
standard
therapy.
It
improved
asthma
symptoms
and
health-related
quality
of
life.
It
also
reduced
exacerbations
and
daily
inhaled
corticosteroid
dose.
5
Response
to
omalizumab
was
better
in
asthmatics
with
increased
biomarkers
of
T2
immunity
and
eosinophilic
inflammation
including
serum
periostin,
blood
eosinophil
count
and
fraction
of
exhaled
nitric
oxide.
6
Anti-interleukin-5
(IL-5)
monoclonal
antibodies
are
the
sec-
ond
class
of
biological
therapy
for
severe
eosinophilic
asthma.
IL-5
cytokine
plays
an
important
role
in
the
maturation
and
∗
Corresponding
author.
E-mail
address:
ceb17@le.ac.uk
(C.E.
Brightling).
activation
of
eosinophils.
Mepolizumab
is
a
humanized
mono-
clonal
antibody
that
binds
to
IL-5,
preventing
it
from
binding
to
IL-5
receptors.
The
first
large
phase
IIb/III
trial
(DREAM
study)
showed
that
mepolizumab
at
a
range
of
doses
significantly
reduced
severe
exacerbation
rate
in
subjects
with
recurrent
exacerbations
and
evidence
of
eosinophilic
inflammation.
7
The
results
were
also
replicated
in
another
phase
III
trial
using
a
lower
intra-
venous
Mepolizumab
dose
of
75
mg
and
a
subcutaneous
dose
of
100
mg.
8
Mepolizumab
has
also
been
shown
to
have
steroid-
sparing
effects
by
significantly
reducing
daily
systemic
corticos-
teroid
use
compared
to
placebo,
while
maintaining
its
exacerbation
reduction
effect.
9
The
efficacy
of
mepolizumab
appeared
to
be
more
pronounced
in
subjects
with
higher
baseline
blood
eosinophil
levels
and
more
frequent
exacerbations,
with
no
benefit
in
exacerbation
reduction
in
those
with
a
blood
eosinophil
count
<150
cells/
L.
On
the
strength
of
these
positive
trial
results,
it
has
since
been
licensed
for
use
in
severe
eosinophilic
asthma.
Reslizumab,
another
monoclonal
antibody
targeting
IL-5,
was
also
recently
licensed
for
use
in
severe
eosinophilic
(
≥
400
blood
eosinophils/
L)
asthma
following
phase
III
trials
demonstrating
significant
improvement
in
forced
expiratory
volume
in
1
sec-
ond
(FEV1),
asthma
control
scores,
asthma-related
quality
of
life
and
frequency
of
asthma
exacerbations.
10,11
However,
when
used
across
a
broad
range
of
blood
eosinophil
counts,
reslizumab
had
no
effect
on
lung
function
and
asthma
control.
12
Benralizumab
differs
from
mepolizumab
and
reslizumab
as
it
acts
on
the
alpha
chain
of
the
IL-5
receptor
causing
eosinophil
apoptosis.
Two
recent
phase
III
trials
in
subjects
with
inadequately
controlled
asthma,
frequent
exacerbations
and
elevated
blood
eosinophil
count
showed
sig-
nificant
reduction
of
annual
asthma
exacerbation
rate
compared
to
placebo.
13,14
It
also
significantly
improved
FEV1,
Asthma
Con-
trol
Questionnaire
(ACQ)
and
Asthma
Quality
of
Life
Questionnaire
(AQLQ)
scores
in
those
receiving
the
treatment
every
8
weeks.
Inhibiting
other
T2-cytokines
such
as
IL-13
neutralization
(Lebrikizumab
and
Tralokinumab)
or
the
alpha
chain
of
the
IL-4
receptor
which
attenuates
both
IL-4
and
IL-13
signaling
(Dupilumab)
are
attractive
targets.
None
of
these
strategies
have
demonstrated
an
effect
on
reducing
eosinophilic
inflammation,
but
benefits
for
these
approaches
are
greater
in
those
with
upregulated
T2-immunity
and
eosinophilic
inflammation.
Recent
http://dx.doi.org/10.1016/j.arbres.2017.01.012
0300-2896/©
2017
SEPAR.
Published
by
Elsevier
Espa
̃
na,
S.L.U.
All
rights
reserved.
http://dx.doi.org/10.1016/j.arbr.2017.01.017
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