Pharmaceuticals,
Год журнала:
2021,
Номер
14(10), С. 955 - 955
Опубликована: Сен. 23, 2021
Some
effective
drugs
have
been
approved
or
issued
an
Emergency
Use
Authorization
for
the
treatment
of
COVID-19
in
hospitalized
patients,
but
post-market
surveillance
is
warranted
to
monitor
adverse
events.
We
reviewed
clinical
trials
and
case
reports
patients
with
moderate-to-severe
infection
who
received
remdesivir,
baricitinib,
tocilizumab,
sarilumab.
The
drug-specific
pharmacokinetics,
toxicity,
drug
interactions
are
summarized
this
study.
Remdesivir
baricitinib
small-molecule
that
mainly
metabolized
by
kidneys,
while
tocilizumab
sarilumab
monoclonal
antibody
metabolic
pathways
currently
not
fully
understood.
most
common
events
these
alterations
liver
function,
serious
rarely
attributed
them.
Only
a
few
studies
reported
remdesivir
might
be
cardiotoxic
cause
thromboembolism.
Biological
agents
such
as
could
inhibit
pathway
inflammatory
processes,
leading
immune
dysregulation,
so
risk
secondary
should
assessed
before
prescribing.
Further
recognition
pathogenic
mechanism
factors
essential
optimizing
strategies.
The Lancet Respiratory Medicine,
Год журнала:
2021,
Номер
9(12), С. 1427 - 1438
Опубликована: Окт. 29, 2021
SummaryBackgroundInfections
with
SARS-CoV-2
continue
to
cause
significant
morbidity
and
mortality.
Interleukin
(IL)-1
IL-6
blockade
have
been
proposed
as
therapeutic
strategies
in
COVID-19,
but
study
outcomes
conflicting.
We
sought
whether
of
the
or
IL-1
pathway
shortened
time
clinical
improvement
patients
hypoxic
respiratory
failure,
signs
systemic
cytokine
release
syndrome.MethodsWe
did
a
prospective,
multicentre,
open-label,
randomised,
controlled
trial,
hospitalised
hypoxia,
syndrome
across
16
hospitals
Belgium.
Eligible
had
proven
diagnosis
COVID-19
symptoms
between
6
days,
ratio
partial
pressure
oxygen
fraction
inspired
(PaO2:FiO2)
less
than
350
mm
Hg
on
room
air
280
supplemental
oxygen,
their
serum
(either
single
ferritin
measurement
more
2000
μg/L
immediately
requiring
high
flow
mechanical
ventilation,
concentration
1000
μg/L,
which
increasing
over
previous
24
h,
lymphopenia
below
800/mL
two
following
criteria:
an
700
lactate
dehydrogenase
300
international
units
per
L,
C-reactive
protein
70
mg/L,
D-dimers
ng/mL).
The
COV-AID
trial
has
2
×
factorial
design
evaluate
versus
no
blockade.
Patients
were
randomly
assigned
by
means
permuted
block
randomisation
varying
size
stratification
centre.
In
first
randomisation,
receive
subcutaneous
anakinra
once
daily
(100
mg)
for
28
days
until
discharge,
(1:2).
second
step,
allocated
dose
siltuximab
(11
mg/kg)
intravenously,
tocilizumab
(8
(1:1:1).
primary
outcome
was
improvement,
defined
from
increase
at
least
points
6-category
ordinal
scale
discharge
hospital
alive.
supportive
efficacy
endpoints
assessed
intention-to-treat
population.
Safety
safety
This
is
registered
online
ClinicalTrials.gov
(NCT04330638)
EudraCT
(2020-001500-41)
complete.FindingsBetween
April
4,
Dec
6,
2020,
342
(n=112)
(n=230)
simultaneously
(n=227;
114
113
siltuximab)
(n=115).
Most
male
(265
[77%]
342),
median
age
65
years
(IQR
54–73),
Systematic
Organ
Failure
Assessment
(SOFA)
score
3
(2–4).
All
included
analysis.
estimated
12
(95%
CI
10–16)
group
(10–15)
(hazard
[HR]
0·94
[95%
0·73–1·21]).
For
group,
11
(11–16)
(HR
1·00
[0·78–1·29]).
55
died
during
study,
evidence
differences
mortality
treatment
groups
found.
incidence
serious
adverse
events
infections
similar
groups.InterpretationDrugs
targeting
not
shorten
this
sample
low
SOFA
score,
baseline
risk.FundingBelgian
Health
Care
Knowledge
Center
VIB
Grand
Challenges
program.
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Фев. 22, 2022
Acting
on
the
cytokine
cascade
is
key
to
preventing
disease
progression
and
death
in
hospitalised
patients
with
COVID-19.
Among
anti-cytokine
therapies,
interleukin
(IL)-6
inhibitors
have
been
most
used
studied
since
beginning
of
pandemic.
Going
through
previous
observational
studies,
subsequent
randomised
controlled
trials,
meta-analyses,
we
focused
baseline
characteristics
recruited,
identifying
favourable
features
light
positive
or
negative
study
outcomes;
taking
into
account
biological
significance
predictivity
IL-6
other
biomarkers
according
specific
thresholds,
ultimately
attempted
delineate
precise
windows
for
therapeutic
intervention.
By
stimulating
scavenger
macrophages
T-cell
responsivity,
seems
protective
against
viral
replication
during
asymptomatic
infection;
still
early
tissue
damage
by
modulating
release
granzymes
lymphokines
mild-moderate
disease;
importantly
pathogenic
severe
inducing
proinflammatory
activation
immune
endothelial
cells
(through
trans-signalling
trans-presentation);
again
critical
exerting
homeostatic
roles
repair
cis-signalling),
while
IL-1
drives
hyperinflammation.
inhibitors,
particularly
anti-IL-6R
monoclonal
antibodies
(e.g.,
tocilizumab,
sarilumab),
are
effective
disease,
characterised
concentrations
ranging
from
35
90
ng/mL
(reached
circulation
within
6
days
hospital
admission),
a
ratio
partial
pressure
arterial
oxygen
(PaO2)
fraction
inspired
(FiO2)
between
100
200
mmHg,
requirement
high-flow
non-invasive
ventilation,
C-reactive
protein
levels
120
160
mg/L,
ferritin
800
1600
ng/mL,
D-dimer
750
3000
lactate
dehydrogenase
350
500
U/L.
Granulocyte-macrophage
colony-stimulating
factor
might
similar
opportunity
but
different
age
preferences
compared
(over
under
70
years
old,
respectively).
Janus
kinase
baricitinib)
may
also
be
moderate
whereas
anakinra)
disease.
Correct
use
biologics
based
essential
successful
outcomes
could
inform
future
new
trials
more
appropriate
recruiting
criteria.
Cancers,
Год журнала:
2022,
Номер
14(2), С. 429 - 429
Опубликована: Янв. 15, 2022
Interleukin
(IL)-6
family
cytokines,
such
as
IL-6
and
IL-11,
are
defined
by
the
shared
use
of
gp130
receptor
for
downstream
activation
STAT3
signaling
genes
which
contribute
to
"hallmarks
cancer",
including
proliferation,
survival,
invasion
metastasis.
Increased
expression
these
or
ligand-specific
receptors
IL-6R
IL-11RA,
in
breast
tumors
positively
correlate
disease
progression
poorer
patient
outcome.
In
this
review,
we
examine
evidence
from
pre-clinical
studies
that
enhanced
IL-11
mediated
gp130/STAT3
cancer.
Key
processes
cytokines
heterogeneous
nature
cancer,
immune
evasion
metastatic
potential,
discussed.
We
latest
research
into
therapeutic
targeting
inhibit
transcriptional
activity
a
potential
cancer
treatment,
current
clinical
trials.
The
importance
cellular
promote
development
warrants
further
understanding
molecular
basis
its
actions
help
guide
future
targets.
Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy,
Год журнала:
2021,
Номер
41(11), С. 884 - 906
Опубликована: Сен. 24, 2021
The
results
of
studies
tocilizumab
(TCZ)
in
COVID-19
are
contradictory.
Our
study
aims
to
update
medical
evidence
from
controlled
observational
and
randomized
clinical
trials
(RCTs)
on
the
use
TCZ
hospitalized
patients
with
COVID-19.
Journal of the American Heart Association,
Год журнала:
2024,
Номер
13(4)
Опубликована: Фев. 13, 2024
Multisystemic
inflammatory
syndrome
in
adults
is
a
hyperinflammatory
condition
following
(within
4-12
weeks)
SARS-CoV-2
infection.
Here,
the
dysregulation
of
immune
system
leads
to
multiorgan
involvement
often
affecting
heart.
Cardiac
multisystemic
has
been
described
mainly
young
men
without
other
comorbidities
and
may
present
with
different
clinical
scenarios,
including
acute
heart
failure,
life-threatening
arrhythmias,
pericarditis,
myocarditis,
nonnegligible
risk
mortality
(up
7%
all
cases).
The
heterogeneity
its
features
absence
clear
case
definition
make
differential
diagnosis
postinfectious
(eg,
infective
myocarditis)
diseases
adult
Still
disease
macrophage
activation
syndrome)
challenging.
Moreover,
evidence
on
efficacy
specific
treatments
targeting
response
underlying
this
glucocorticoids,
immunoglobulins,
immunomodulatory
agents)
sparse
not
supported
by
randomized
trials.
In
review
article,
we
aim
provide
an
overview
diagnostic
workup
cardiac
involvement,
highlighting
possible
pathogenetic
mechanisms
therapeutic
management,
along
remaining
knowledge
gaps
field.