Advances in Therapy,
Год журнала:
2023,
Номер
40(12), С. 5547 - 5556
Опубликована: Сен. 30, 2023
Patient-reported
outcomes
(PROs)
provide
an
insightful
method
of
assessing
the
subjective
impact
therapies
for
those
affected
by
multiple
sclerosis
(MS),
a
chronic
neurologic
disease
notable
symptoms
fatigue
and
reduced
physical
function.
The
ongoing
CLAWIR
study
aims
to
assess
effect
cladribine
tablets
(3.5
mg/kg
cumulative
dose
over
2
years)
in
patients
with
highly
active
relapsing
MS
focusing
on
PROs
fatigue,
function,
treatment
satisfaction,
work
productivity.
Here,
we
report
pre-planned
analysis
at
12
months
after
initiation
tablets.
is
2-year,
multicenter,
prospective,
observational
newly
initiating
following
were
analyzed:
PRO
Measurement
Information
System
(PROMIS®)
Fatigue
(v1.0)
Physical
Function
(v2.1),
Treatment
Satisfaction
Questionnaire
Medication
(TSQM,
v1.4),
Work
Productivity
Activity
Impairment
(WPAI-MS).
Data
analyzed
descriptively.
In
total,
128
eligible
analysis:
95
females
(74.2%);
median
(range)
age
34.5
(29,
44)
years;
34
(26.6%)
treatment-naïve,
89
(69.5%)
early
switchers
from
platform
(the
remaining
5
[3.9%]
switched
high-efficacy
disease-modifying
therapy).
PROMIS®
mean
(±
standard
deviation
[SD])
T-scores
decreased
54.6
9.59)
baseline
51.8
10.30)
months,
indicating
alleviation
whereas
remained
stable
time
[baseline:
49.4
10.69);
months:
50.3
10.88)].
TSQM
v1.4
scores
indicated
improvement
time,
increasing
52.2
27.79)
81.4
17.06)
global
satisfaction.
WPAI-MS
also
showed
across
all
four
domains
months.
This
real-world
demonstrates
registered
German
Federal
Institute
Drugs
Medical
Devices
internal
NIS
number
7469.
Journal of Neurology,
Год журнала:
2023,
Номер
270(7), С. 3553 - 3564
Опубликована: Апрель 7, 2023
Abstract
Introduction
Cladribine
is
approved
for
the
treatment
of
active
relapsing
MS
(RRMS),
but
its
positioning
in
therapeutic
scenario
still
needs
to
be
fully
elucidated.
Methods
This
a
monocentric,
observational,
real-world
study
on
RRMS
patients
treated
with
cladribine.
Relapses,
magnetic
resonance
imaging
(MRI)
activity,
disability
worsening,
and
loss
no-evidence-of-disease-activity-3
(NEDA-3)
status
were
assessed
as
outcomes.
White
blood
cell,
lymphocyte
counts
side
effects
also
evaluated.
Patients
analyzed
overall
subgroups
according
last
before
The
relationship
between
baseline
characteristics
outcomes
was
tested
identify
predictors
response.
Results
Among
114
included,
74.9%
NEDA-3
at
24
months.
We
observed
reduction
relapses
MRI
along
stabilization
disability.
A
higher
number
gadolinium-enhancing
lesions
only
risk
factor
during
follow-up.
more
efficacious
switchers
from
first-line
therapies
or
naïves.
Grade
I
lymphopenia
frequent
month
3
15.
No
grade
IV
cases
observed.
Independent
III
lower
count
previous
treatments.
Sixty-two
presented
least
one
effect
globally
111
adverse
events
recorded,
none
them
serious.
Conclusions
Our
confirms
data
cladribine
effectiveness
safety.
effective
when
placed
early
algorithm.
Real-world
larger
populations
longer
follow-up
are
needed
confirm
our
findings.
Neurology and Therapy,
Год журнала:
2023,
Номер
12(6), С. 1909 - 1935
Опубликована: Окт. 11, 2023
The
emergence
of
high-efficacy
therapies
for
multiple
sclerosis
(MS),
which
target
inflammation
more
effectively
than
traditional
disease-modifying
therapies,
has
led
to
a
shift
in
MS
management
towards
achieving
the
outcome
assessment
known
as
no
evidence
disease
activity
(NEDA).
most
common
NEDA
definition,
termed
NEDA-3,
is
composite
three
related
measures
activity:
clinical
relapses,
disability
progression,
and
radiological
activity.
been
frequently
used
endpoint
trials,
but
there
growing
interest
its
use
an
tool
help
patients
healthcare
professionals
navigate
treatment
decisions
clinic.
Raising
awareness
about
may
therefore
clinicians
make
informed
around
improve
overall
care.
This
review
aims
explore
potential
utility
decision-making
by
summarizing
literature
on
current
context
expanding
landscape.
We
identify
challenges
practice
detail
proposed
amendments,
such
inclusion
alternative
outcomes
biomarkers,
broaden
information
captured
NEDA.
These
themes
are
further
illustrated
with
real-life
perspectives
experiences
our
two
patient
authors
MS.
intended
be
educational
resource
support
discussions
between
this
evolving
approach
MS-specialized
Recent
progress
(MS)
development
new
treatments,
therapies.
Compared
previous
better
at
managing
visible
central
nervous
system,
main
cause
worsening
symptoms
early
people
living
Treatment
means
many
achieve
previously
possible.
One
set
criteria
Achieving
commonly
criteria,
that
exhibit
physical
symptoms,
magnetic
resonance
imaging
scan.
Researchers
have
studied
it
useful
doctors
measure
person's
progression
response
treatment.
could
inform
important
selection
care
explores
available
understand
evaluations.
discuss
barriers
being
ways
change
capture
broader
range
from
patient.
topics
presented
alongside
meant
assist
conversations
everyday
practice.
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
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Фев. 9, 2024
Background
Cladribine
has
been
introduced
as
a
high-efficacy
drug
for
treating
relapsing-remitting
multiple
sclerosis
(RRMS).
Initial
cohort
studies
showed
early
disease
activity
in
the
first
year
after
initiation.
Biomarkers
that
can
predict
are
needed.
Aim
To
estimate
cerebrospinal
fluid
(CSF)
markers
of
clinical
and
radiological
responses
initiation
cladribine.
Methods
Forty-two
RRMS
patients
(30F/12M)
treated
with
cladribine
were
included
longitudinal
prospective
study.
All
underwent
CSF
examination
at
treatment
initiation,
follow-up
including
Expanded
Disability
Status
Scale
(EDSS)
assessment,
3T
MRI
scan
6,12
24
months,
evaluation
white
matter
(WM)
cortical
lesions
(CLs).
levels
67
inflammatory
assessed
immune-assay
multiplex
techniques.
The
‘no
evidence
activity’
(NEDA-3)
status
was
two
years
defined
by
no
relapses,
disability
worsening
measured
EDSS
activity,
CLs.
Results
Three
lost
follow-up.
At
end
follow-up,
19
(48%)
remained
free
from
activity.
IFNgamma,
Chitinase3like1,
IL32,
Osteopontin,
IL12(p40),
IL34,
IL28A,
sTNFR2,
IL20
CCL2
best
association
When
added
multivariate
regression
model
age,
sex,
baseline
EDSS,
Chitinase
3
like1
(p
=
0.049)
significantly
increased
those
Finally,
ROC
analysis
Chitinase3like1
to
age
previous
WM
lesion
number,
CLs,
number
Gad
enhancing
spinal
cord
provided
an
AUC
0.76
(95%CI
0.60-0.91).
Conclusions
might
provide
prognostic
information
predicting
drug’s
effect
on
chronic
macrophage
microglia
activation
deserves
further
evaluation.
Neurology and Therapy,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 4, 2025
The
emergence
of
high-efficacy
disease-modifying
therapies
(HE
DMT)
for
multiple
sclerosis
(MS)
may
pose
challenges
to
the
administration
and
monitoring
burden
therapies.
This
article
presents
results
Delphi
consensus
method
generate
insights
from
experts
on
HE
DMT
in
Saudi
Arabia
with
a
special
focus
cladribine.
Between
January
March
2023,
two-round
modified
was
used
establish
regarding
DMTs
MS.
Through
questionnaire,
advisors
evaluated
17
properties
six
individual
basis
their
clinical
experience.
Advisors
were
required
rank
each
property
scale
1–5,
1
being
lowest
5
highest
burden.
Experts
ranked
cladribine
as
having
burden,
followed
by
ofatumumab
ocrelizumab.
Natalizumab
fingolimod
fourth,
alemtuzumab
had
During
first
round,
agreed
scores
properties,
except
hospital
visit
time
facility
use
during
ofatumumab,
route
fingolimod,
specific
side
effects
frequency
lab
tests
at
follow-up,
washout
period
natalizumab.
second
there
agreement
all
properties.
In
absence
alternative
scientific
data,
recommendations
provide
useful
into
MS
Arabia.
Therapeutic Advances in Neurological Disorders,
Год журнала:
2025,
Номер
18
Опубликована: Янв. 1, 2025
Background:
Characterizing
Cladribine
tablets
prescription
pattern
in
daily
clinical
practice
is
crucial
for
optimizing
multiple
sclerosis
(MS)
treatment.
Objectives:
To
describe
efficacy,
safety
profile
and
new
disease-modifying
therapy
(DMT)
prescriptions
following
Design:
Independent
retrospective
cohort
study
patients
followed
at
six
Italian
MS
centres.
Methods:
Patients
diagnosed
with
relapsing
(RMS)
according
to
2017
McDonald
criteria,
who
initiated
between
January
2019
May
2023,
were
included.
A
generalized
linear
regression
model
was
built
the
outcome
DMT
after
course.
Heatmaps
generated
based
on
weighted
pivot
tables
visualize
proportion
of
requiring
post-Cladribine.
Results:
total
352
enrolled,
134
naïve
any
DMT,
218
switchers
from
other
DMTs.
The
last
an
injectable
first-line
48
(22%)
patients,
oral
141
(64.7%)
SP1
inhibitor-Fingolimod
23
(10.6%)
Natalizumab
6
(2.7%)
patients.
Overall,
efficacious
well
tolerated,
12%
required
a
median
time
24
months.
revealed
that
aged
>40
years
had
16%
decrease
likelihood
receiving
DMT.
showed
previously
Fingolimod
lower
rate
(72.2%)
being
free
Cladribine.
Conclusion:
In
our
multicentric
real-world
study,
generally
effective
during
investigated
follow-up
period.
Understanding
key
characteristics
responding
best
can
help
tailor
therapeutic
strategies
optimal
outcomes.
Therapeutic Advances in Neurological Disorders,
Год журнала:
2025,
Номер
18
Опубликована: Янв. 1, 2025
Background:
Alemtuzumab
is
a
disease-modifying
therapy
for
highly
active
relapsing-remitting
multiple
sclerosis
(RRMS).
Sustained
efficacy
up
to
9
years
was
observed
in
the
phase
IIIb/IV
open-label
TOPAZ
clinical
trial
and
assessed
real-world
retrospective
prospective
study,
TREAT-MS.
Objectives:
To
examine
long-term
safety
of
alemtuzumab
participants
with
(MS)
disease
(HAD)
by
combining
13
data
TREAT-MS
interim
data.
Design:
TOPAZ:
Randomized
completing
core
CARE-MS
I
II
could
receive
additional
(12
mg/day,
3
consecutive
days;
⩾12
months
apart)
11–13
after
initiating
treatment.
TREAT-MS:
Participants
from
German
MS
clinics
were
4
last
treatment
phase.
Methods:
Efficacy
outcomes
(annualized
relapse
rate
(ARR),
change
Expanded
Disability
Status
Scale
(EDSS),
6-month
confirmed
disability
worsening/improvement,
magnetic
resonance
imaging),
adverse
events
(AEs)
examined.
Primary
HAD
definition
(⩾2
relapses
year
prior
baseline
⩾1
gadolinium-enhancing
lesion
at
baseline),
two
alternative
definitions
assessed.
Results:
More
(28%)
(24%)
met
primary
criteria
than
(~14%).
Mean
ARR
alemtuzumab-treated
significantly
reduced
(0.14
0.15,
respectively,
Years
3–13)
(0.24,
>2
years).
Stable/improved
EDSS
scores
achieved
74%
I,
67%
(both
Year
11),
79%
(Year
3.6),
CDI
about
half
11
(CARE-MS
II).
Annual
treatment-emergent
AE
incidences
declined
lower
Conclusion:
radiological
study
no
new
signals.
Trial
registration:
ClinicalTrials.gov
NCT00530348;
II,
NCT00548405;
Extension
Study,
NCT00930553;
TOPAZ,
NCT02255656).
Paul-Ehrlich-Institut
(TREAT-MS,
NIS
281).
Neurology and Therapy,
Год журнала:
2022,
Номер
12(1), С. 25 - 37
Опубликована: Ноя. 17, 2022
Based
on
the
results
of
pivotal
CLARITY
study,
cladribine
tablets
were
approved
for
use
in
European
Union
2017
as
a
high-efficacy
therapy
highly
active
relapsing-remitting
multiple
sclerosis
(MS).
Cladribine
are
used
an
induction
therapy:
half
total
dose
is
given
year
1
and
other
2.
In
Extension
trials,
repeating
routinely
years
3
4,
was
not
associated
with
significantly
improved
disease
control.
However,
there
very
limited
evidence
how
to
manage
people
MS
(pwMS)
beyond
which
increasingly
important
because
more
patients
now
≥
4
after
treatment.
Overall,
postapproval
data
show
that
treatment
two
cycles
effectively
controls
activity
long
term.
general
agreement
some
pwMS
suboptimal
response
could
benefit
from
retreatment.
This
study
reviews
practical
aspects
using
tablets,
summarizes
clinical
trials
real-world
studies
safety
efficacy
cladribine,
proposes
algorithm
developed
by
expert
consensus
previously
treated
cladribine.
brief,
we
propose
additional
courses
should
be
considered
minimal
(no
relapses,
1-2
new
lesions)
or
moderate
(1
relapse,
3-4
activity,
while
significant
(>
>
progression
warrant
switch
another
(HET).
More
needed
improve
guidelines
who
received
Neurology and Therapy,
Год журнала:
2023,
Номер
12(5), С. 1457 - 1476
Опубликована: Июнь 29, 2023
Cladribine
tablets
(CladT)
is
a
highly
active
oral
disease-modifying
therapy
(DMT)
for
the
management
of
relapsing
multiple
sclerosis
(RMS).
CladT
acts
as
an
immune
reconstitution
therapy,
in
that
two
short
courses
treatment
1
year
apart
have
been
shown
to
suppress
disease
activity
prolonged
period
most
patients,
without
need
continued
DMT.
Each
course
induces
profound
reduction
B
lymphocytes
recovers
over
months,
and
serious
lymphopenia
(Grade
3–4)
uncommon.
Smaller
reductions
levels
T
occur
slightly
later:
on
average,
these
remain
within
normal
range
repopulate
progressively.
A
larger
effect
occurs
CD8
vs.
CD4
cells.
Reactivation
latent
or
opportunistic
infections
(e.g.
varicella
zoster,
tuberculosis)
mostly
associated
with
very
low
lymphocyte
counts
(<
200/mm3).
Screening
managing
pre-existing
infections,
vaccinating
non-exposed
patients
delaying
2nd
allow
recover
>
800/mm3
(if
necessary)
are
important
avoiding
higher-grade
lymphopenia.
There
was
no
demonstrable
apparent
efficacy
vaccinations,
including
against
Covid-19.
Adverse
events
consistent
drug-induced
liver
injury
(DILI)
represent
rare
but
potentially
complication
spontaneous
adverse
event
reporting;
should
be
screened
dysfunction
before
starting
treatment.
Ongoing
hepatic
monitoring
not
required,
must
withdrawn
if
signs
symptoms
DILI
develop.
numerical
imbalance
malignancies
when
comparing
cladribine
placebo
clinical
programme,
particularly
short-term
data,
recent
evidence
shows
risk
malignancy
similar
background
rate
general
population
other
DMTs.
Overall,
well
tolerated
favorable
safety
profile
appropriate
RMS.