Page 164 - 80_01

Basilio
Colligris,
Jesús
Pintor

BELIMUMAB

Belimumab
is
a
human
monoclonal
antibody
inhibiting
B-­-cell
activating

factor
(BAFF)
and
is
developed
by
the
University
of
Udine
as
a
treatment
for

Sjögren’s
syndrome.
Sjögren's
syndrome
is
a
systemic
autoimmune
disease

characterized
by
an
increase
in
BAFF
(BLyS)
levels
resulting
in
B
cell
hyperactivity.

B
cells
are
involved
in
the
pathogenesis
of
SS
in
both
systemic
and
glandular

features,
and
B
cell
down
regulation
may
lead
to
a
decrease
of
disease
activity.

Moreover,
pathogenesis
of
SS
is
closed
to
that
of
systemic
lupus
erythematosus,

where
belimumab
has
been
proven
to
be
effective.
Currently
the
compound
is

under
Phase
II
clinical
trials
evaluation
(ClinicalTrials.gov
Identifier:

NCT01160666)
and
the
initial
results
are
promising
(56).

RITUXIMAB

Rituximab
(CD20)
is
developed
by
IDEC
Pharmaceuticals
as
a
treatment
for

Sjögren’s
syndrome.
CD20
antigen
is
targeting
cells
of
the
B-­-cell
lineage,
leading
to

transient
blood
B-­-cell
depletion,
leaving
aside
stem
cells
(57).
Rituximab
is
already

approved
by
the
U.S.
Food
and
Drug
Administration
in
1997
as
a
treatment
of
B-­-
cell
non-­-Hodgkin
lymphomas
resistant
to
other
chemotherapy
regimens.
The

compound
currently
is
tested
in
Phase
III
clinical
trials
(ClinicalTrials.gov

Identifier:
NCT00740948)
to
study
the
tolerance
and
efficacy
of
rituximab
injection

in
Sjögren’s
disease
(58,
59).

LOTEMAX

Bausch
&
Lomb,
Inc.
is
re-­-purposing
the
already
approved
drug
Lotemax

with
topical
cyclosporine
ophthalmic
emulsion
0.05%
(Restasis)
as
a
possible

treatment
of
dry
eye.
Lotemax
(loteprednoletabonate-­-LE)
(Figure
7)
(60)
is
an

ester
corticosteroid
with
a
high
therapeutic
index,
containing
an
ester
rather
than

a
ketone,
at
carbon-­-20
of
the
prednisolone
core
structure.
LE
is
indicated
for
the

treatment
of
steroid
responsive
inflammatory
conditions
associated
to
the

palpebral
and
bulbar
conjunctiva,
cornea,
and
anterior
segment
of
the
globe.
Its

mechanism
of
action
is
to
block
the
inflammatory
mediators
treating
the

inflammation
associated
with
the
dry
eye
disease.
Cyclosporine
A
as
already

mentioned
above
is
a
standard
molecule
against
inflammation
with
efficacy
in
dry

eye
disease,
enhancing
or
restoring
the
lachrymal
gland
secretion
in
patients

suffering
from
this
syndrome
(61).
An
advantage
of
topical
loteprednol

160