Degenerative Neurological and Neuromuscular Disease,
Год журнала:
2023,
Номер
Volume 13, С. 81 - 88
Опубликована: Дек. 1, 2023
The
increasing
availability
of
high-efficacy
disease-modifying
therapies
(DMT)
for
the
management
relapsing
multiple
sclerosis
(RMS)
has
increased
potential
individualised
patient
but
added
complexity
to
design
treatment
regimens.
long-term
application
immune
reconstitution
therapy
(IRT)
is
supported
by
an
database
real
world
studies
that
have
important
information
on
safety
and
efficacy
this
approach.
Cladribine
tablets
(CladT)
IRT
given
as
two
annual
short
courses
treatment,
following
which
a
majority
patients
then
demonstrate
no
significant
MS
disease
activity
over
period
years.
Whether,
how,
treat
beyond
first
years
remains
matter
debate,
clinical
evidence
accumulates.
We,
group
neurologists
who
manage
people
with
RMS
in
Qatar,
provide
our
expert
consensus
recommendations
CladT
based
experience
last
5
These
include
pragmatic
3
4
(ie
up
four
dose
CladT),
or
without
subsequent
We
believe
will
help
ensure
optimal
CladT-based
IRT,
benefit
achieving
prolonged
periods
free
both
symptoms
burden
regular
applications
immunosuppressive
DMT.
CNS Drugs,
Год журнала:
2024,
Номер
38(4), С. 267 - 279
Опубликована: Март 15, 2024
Numerous
therapies
are
currently
available
to
modify
the
disease
course
of
multiple
sclerosis
(MS).
Magnetic
resonance
imaging
(MRI)
plays
a
pivotal
role
in
assessing
treatment
response
by
providing
insights
into
activity
and
clinical
progression.
Integrating
MRI
findings
with
laboratory
data
enables
comprehensive
assessment
course.
Among
MS
treatments,
cladribine
is
emerging
as
promising
option
due
its
selective
immune
reconstitution
therapy,
notable
impact
on
B
cells
lesser
effect
T
cells.
This
work
emphasizes
MRI's
contribution
treatment,
particularly
focusing
influence
tablets
outcomes,
encompassing
from
real-world
studies.
The
evidence
highlights
that
cladribine,
compared
placebo,
not
only
exhibits
reduction
inflammatory
markers,
such
T1-Gd+,
T2
combined
unique
active
(CUA)
lesions,
but
also
mitigates
brain
volume
loss,
within
grey
matter.
Importantly,
reveals
early
action
reducing
CUA
lesions
first
months
regardless
patient's
initial
conditions.
mechanism
action,
sustained
efficacy
beyond
year
2,
onset
collectively
position
component
therapeutic
paradigm
for
MS.
Overall,
MRI,
along
measures,
has
played
substantial
showcasing
effectiveness
addressing
both
neurodegenerative
aspects
Therapeutic Advances in Neurological Disorders,
Год журнала:
2023,
Номер
16
Опубликована: Янв. 1, 2023
Cladribine
is
an
effective
immunotherapy
for
people
with
multiple
sclerosis
(pwMS).
Whilst
most
pwMS
do
not
require
re-treatment
following
standard
dosing
(two
treatment
courses),
disease
activity
re-emerges
in
others.
The
characteristics
of
developing
re-emerging
remain
incompletely
understood.To
explore
whether
clinical
and/or
paraclinical
baseline
characteristics,
including
the
degree
lymphocyte
reduction,
drug
dose
and
lesions
on
magnetic
resonance
imaging
(MRI)
are
associated
activity.Service
evaluation
undergoing
subcutaneous
cladribine
(SClad)
treatment.Demographics,
clinical,
laboratory
MRI
data
receiving
two
courses
SClad
were
extracted
from
health
records.
To
assess
associations
predictor
variables
activity,
a
series
Cox
proportional
hazards
models
was
fitted
(one
each
variable).Of
n
=
264
236
received
included
analysis.
Median
follow-up
4.5
years
(3.9,
5.3)
first,
3.5
(2.9,
4.3)
last
administration.
Re-emerging
occurred
57/236
(24%);
22/236
further
doses
(SClad
or
tablets)
at
36.7
months
[median;
interquartile
range
(IQR):
31.7,
42.1],
other
immunotherapies
18.9
(13.0,
30.2)
after
their
second
course
SClad,
respectively.
Eligibility
based
29,
relapse
5,
both
13,
elevated
cerebrospinal
fluid
neurofilament
light
chain
level
3,
deterioration
unrelated
to
4
3.
Only
36/57
those
eligible
additional
had
reduced
course.
Association
detected
between
(i)
high
(ii)
low
SClad.Re-emerging
SClad.
Neurology and Therapy,
Год журнала:
2024,
Номер
13(3), С. 503 - 518
Опубликована: Март 15, 2024
Cladribine
tablets
(CladT)
has
been
available
for
therapeutic
use
in
France
since
March
2021
the
management
of
highly
active
relapsing
multiple
sclerosis
(RMS).
This
high-efficacy
disease-modifying
therapy
(DMT)
acts
as
an
immune
reconstitution
therapy.
In
contrast
to
most
DMTs,
which
act
via
continuous
immunosuppression,
two
short
courses
oral
treatment
with
CladT
at
beginning
years
1
and
2
provide
long-term
control
MS
disease
activity
responders
treatment,
without
need
any
further
pharmacological
several
years.
Although
labelling
does
not
guidance
beyond
initial
courses,
real-world
data
on
from
registries
previous
clinical
trial
participants
patients
treated
routine
practice
indicate
that
is
controlled
a
period
this
time
substantial
proportion
patients.
Moreover,
experience
provided
useful
information
how
initiate
manage
CladT.
article
we,
group
expert
neurologists
France,
recommendations
initiation
DMT-naïve
patients,
switch
existing
DMTs
continuing
activity,
during
first
finally,
or
3,
4
after
initiating
We
believe
optimisation
its
will
maximise
benefits
especially
early
course
when
suppression
focal
inflammation
CNS
priority
limit
progression.
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 29, 2024
Abstract
Recently
it
has
been
shown
that
treatments
targeting
B
cells
in
multiple
sclerosis
(MS)
are
effective
controlling
disease
activity.
contribute
to
the
pathogenesis
of
MS
via
antigen
presentation,
T
cell
activation,
and
antibody
production.
In
chronic
progressive
cladribine
trial,
some
patients
treated
with
had
a
significant
decline
oligoclonal
band
number.
However,
mode
action
tablets
(CladT)
on
peripheral
immune
its
biological
activity
within
CNS
remains
be
determined
further.
The
CladB
study
is
longitudinal
prospective
investigation
CladT
treatment
relapsing-remitting
(RRMS).
Blood
was
sampled
at
Day
0,
1,
5,
then
once
week
for
8
weeks,
fortnightly
up
24
month
till
96
weeks
cells.
This
compared
historical
cohort
alemtuzumab
samples
one
month.
Paired
cerebrospinal
fluid
(CSF)
blood
were
also
taken
48
after
initiating
Kappa
Lambda-free
light
chain
(кFLC,
λFLC)
index,
bands
(OCBs),
immunoglobulin
indices,
inflammatory
mediators
neurofilament
(NfL).
Participants
underwent
clinical
magnetic
resonance
imaging
brain
assessments.
Ten
participants
(3
male,
7
female,
mean
age
35.9
±
10.5
(SD)
Expanded
disability
Status
Scale
2.5
(range
0-6)
baseline
enrolled.
cells,
particular
memory
heavily
depleted
by
CladT.
Alemtuzumab,
conversely
rapidly
both
Although
still
present,
reduction
OCB
numbers
observed
4/10
кFLC
index
reduced
from
164.5
227.1
71.3
84.7
(p=0.002)
64.4
67.3
(p=0.01).
coincided
IgG
[1.1
0.5
baseline,
0.8
0.4
(p=0.014)
0.3
(P=0.02)
weeks]
CSF
CXCL-13
[88.6±
68.4
pg/mL,
39.4
35.2
mg/mL
(p=0.037)
19.1
11.7pg/ml
(p=0.027)].
NfL
levels
only
conclusion,
our
supports
view
works
primarily
depleting
B-cells
antibody-secreting
precursors
RRMS
leading
sustained
effects
intrathecal
production
total
associated
B-cell
chemoattractant
CSF.
Neurology and Therapy,
Год журнала:
2024,
Номер
13(5), С. 1321 - 1335
Опубликована: Авг. 3, 2024
Cladribine
tablets
(CladT),
like
alemtuzumab,
acts
as
an
immune
reconstitution
therapy.
However,
CladT
is
administered
orally
(alemtuzumab
given
by
infusion)
and
without
the
potential
for
serious
side
effects
that
limit
therapeutic
use
of
alemtuzumab
in
multiple
sclerosis
(MS).
Treatment
with
CladT,
initially
short
courses
treatment
1
year
apart,
provides
years
freedom
from
MS
disease
activity
responders
to
treatment.
The
appearance
mild
or
moderate
after
initial
2
may
prompt
careful
follow-up
a
further
course
depending
on
nature
individual
circumstances.
severe
requires
switch
alternative
high-efficacy
disease-modifying
(DMT).
accumulating
data
CladT-treated
people
real-world
studies,
including
those
durations
extending
beyond
treatment,
have
demonstrated
long-term
good
proportion
patients.
This
clinical
experience
has
also
confirmed
generally
safe
well
tolerated.
best
time
prescribe
DMT
subject
debate,
evidence
earlier
versus
later
such
agents
provide
more
effective
protection
disability
progression.
High-efficacy
DMTs
traditionally
been
reserved
high
presentation
breakthrough
one
DMTs,
per
current
product
labels.
latest
studies
suggests
DMT-naïve
patients,
shorter
duration.
