New
multiple
sclerosis
(MS)
patients
treated
with
B-cell-depleting
drugs
or
high-efficacy
therapies
had
lower
relapse
rates
and
fewer
brain
lesions
than
those
treated
with
oral
drugs,
but
at
2
years,
disability
outcomes
were
similar,
prospective
data
from
the
MultipleMS
cohort
showed.

Compared
with
oral
platform
therapies,
B-cell-depleting
therapies
were
associated
with
lower
relapse
incidence
(incidence
rate
ratio
0.38,
95%
CI
0.15–0.92)
and
greater
T2
lesion
volume
reduction
(volume
ratio
0.87,
95%
CI
0.76–0.99),
reported
Fredrik
Piehl,
MD,
PhD,
of
the
Karolinska
Institute
in
Stockholm,
and
colleagues
in


Neurology
Open
Access.
Trends
were
similar
for
high-efficacy
therapies.

Changes
in
disability
scores
and
levels
of
serum
neurofilament
light
(NfL),
a
marker
of
axonal
injury,
did
not
differ
among
groups.
Levels
of
serum
glial
fibrillary
acidic
protein
(GFAP),
a
marker
of
astroglial
activation
or
damage,
decreased
modestly
overall,
with
larger
reductions
with
oral
therapies
and
relatively
higher
levels
in
the
B-cell-depleting
therapy
and
high-efficacy
groups,
Piehl
and
colleagues
wrote.

“The
treatment
groups
already
differed
in
important
patient
characteristics,
suggesting
that
doctors
were
to
some
extent
selecting
treatments
based
on
the
individual
patient,”
Piehl
said
in
a
statement.
“Even
so,
B-cell-depleting
therapies
and
other
strong
treatments
were
linked
to
fewer
relapses
and
fewer
MRI
changes.
But
after
2
years,
we
did
not
see
clear
differences
in
disability
scores.”

The
advent
of
disease-modifying
therapies
(DMTs)
transformed
MS
management,
offering
treatments
that
target
inflammation
and
aim
to
slow
progression,
Piehl
and
colleagues
noted.

“A
major
challenge
is
that
worsening
of
MS
disability
represents
a
delayed
phenomenon
that
is
difficult
to
quantify
in
a
comprehensive
way,”
the
researchers
observed.

Research
has
identified
proxies
that
reflect
the
inflammatory
and
progressive
components
of
MS
biology,
they
said:
NfL
correlates
with
inflammatory
disease
activity
like
relapses
and
new
MRI
lesions,
while

GFAP
seems
closely
linked
to
progression
independent
of
relapse
activity.
“Similarly,
focal
MRI
lesion
accumulation
reflects
acute
inflammation,
while
global
and
regional
atrophy
rates
are
associated
with
progressive
disease
features,”
they
added.

The
MultipleMS
findings
“point
toward
a
poor
ability
of
high-efficacy
therapies
and
B-cell-depleting
therapies
to
reduce
chronic
inflammation
despite
their
strong
effect
against
acute
inflammation,”
noted
Carmen
Tur,
MD,
PhD,
of
the
Multiple
Sclerosis
Centre
of
Catalonia
in
Barcelona,
in
an

accompanying
editorial.

Other
studies
have

failed
to
find
differences
between
high-efficacy
and
moderate-efficacy
DMTs
in
preventing
progression
independent
of
relapse
and
MRI
activity,
Tur
pointed
out.

“Taken
together,
these
results
underscore
an
unmet
therapeutic
need
and
support
the
concept
that
chronic
central
nervous
system-compartmentalized
inflammation
evolves
largely
independently
of
acute
inflammatory
activity,”
she
stated.

“In
this
context,
the
emergence
of
Bruton
tyrosine
kinase
inhibitors
and
anti-CD40
ligand
monoclonal
antibodies,
both
designed
to
target
mechanisms
of
chronic
neuroinflammation,
offers
renewed
hope
to
address
this
challenge,”
she
said.

The
real-world

MultipleMS
study
followed
509
newly
diagnosed
MS
patients
with
no
prior
DMT
exposure
in
seven
European
countries.
Most
participants
(89%)
had
relapsing-remitting
MS,
and
63.9%
were
women.
Mean
baseline
age
was
33
years,
and
follow-up
was
completed
at
2
years.

Participants
were
classified
by
initial
therapy
into
injectable
platform
(17.1%),
oral
platform
(29.9%),
high-efficacy
therapy
(15.5%),
B-cell-depleting
therapy
(19.8%),
or
untreated
(17.7%)
groups:

• Injectable
  platform
  drugs
  were
  interferon-beta
  or
  glatiramer
  acetate
• Oral
  platform
  drugs
  were
  dimethyl
  fumarate
  (Tecfidera)
  or
  teriflunomide
  (Aubagio)
• High-efficacy
  therapies
  were
  fingolimod
  (Gilenya),
  cladribine
  (Mavenclad),
  natalizumab
  (Tysabri),
  or
  alemtuzumab
  (Lemtrada)
• B-cell-depleting
  therapies
  were
  rituximab
  (Rituxan)
  or
  ocrelizumab
  (Ocrevus)

Disability
scores
were
tracked
with
the
Expanded
Disability
Status
Scale
(EDSS),
a
0-10-point
scale
with
lower
values
indicating
less
disability.
The
median
EDSS
score
at
baseline
was
1.5
and
the
median
disease
duration
was
0.66
years.

Baseline
EDSS
scores
were
1.0
for
patients
started
on
injectable
platform
drugs
and
2.0
for
patients
started
on
high-efficacy
or
B-cell-depleting
therapies.
“As
expected,
baseline
characteristics
considerably
influenced
DMT
selection,
partly
because
of
restrictions
on
the
use
of
high-efficacy
therapies,”
Piehl
and
co-authors
noted.

“About
nine
of
10
who
started
B-cell-depleting
therapies
remained
on
the
same
therapy
at
2
years,
compared
with
five
to
seven
of
10
in
other
treatment
groups,
while
more
than
half
of
those
initially
untreated
later
initiated
a
DMT,”
they
reported.

The
study
was
limited
by
its
observational
design
and
lack
of
randomization,
the
researchers
acknowledged.
Outcomes
were
limited
to
2
years.

“Some
treatments
were
linked
to
fewer
attacks
and
fewer
MRI
changes,
and
by
following
this
group
for
several
more
years,
we
will
be
able
to
determine
whether
differences
emerge
over
the
longer
term,”
Piehl
said.

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