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Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch.
[fabry disease]
Because
of
the
shortage
of
agalsidase-
beta
in
2009
,
many
patients
with
Fabry
disease
were
treated
with
lower
doses
or
were
switched
to
agalsidase-alfa
.
This
observational
study
assessed
end-organ
damage
and
clinical
symptoms
during
dose
reduction
or
switch
to
agalsidase-alfa
.
A
total
of
105
adult
patients
with
Fabry
disease
who
had
received
agalsidase-
beta
(
1
.
0
mg
/
kg
body
weight
)
for
≥
1
year
were
nonrandomly
assigned
to
continue
this
treatment
regimen
(
regular-dose
group
,
n
=
38
)
,
receive
a
reduced
dose
of
0
.
3
-
0
.
5
mg
/
kg
(
dose-
reduction
group
,
n
=
29
)
,
or
switch
to
0
.
2
mg
/
kg
agalsidase-alfa
(
switch
group
)
and
were
followed
prospectively
for
1
year
.
We
assessed
clinical
events
(
death
,
myocardial
infarction
,
severe
arrhythmia
,
stroke
,
progression
to
ESRD
)
;
changes
in
cardiac
,
renal
,
and
neurologic
function
;
and
Fabry-related
symptoms
(
neuropathic
pain
,
hypohidrosis
,
diarrhea
,
and
disease
severity
scores
)
.
Organ
function
and
Fabry-related
symptoms
remained
stable
in
the
regular-dose
group
.
In
contrast
,
estimated
GFR
decreased
by
about
3
ml
/
min
per
1
.
73
m
(
2
)
(
P
=
0
.
01
)
in
the
dose-
reduction
group
,
and
the
median
albumin
-
to
-creatinine
ratio
increased
from
114
(
0
-
606
)
mg
/
g
to
216
(
0
-
2062
)
mg
/
g
(
P
=
0
.
03
)
in
the
switch
group
.
Furthermore
,
mean
Mainz
Severity
Score
Index
scores
and
frequencies
of
pain
attacks
,
chronic
pain
,
gastrointestinal
pain
,
and
diarrhea
increased
significantly
in
the
dose-
reduction
and
switch
groups
.
In
conclusion
,
patients
receiving
regular
agalsidase-
beta
dose
had
a
stable
disease
course
,
but
dose
reduction
led
to
worsening
of
renal
function
and
symptoms
.
Switching
to
agalsidase-alfa
is
safe
,
but
microalbuminuria
may
progress
and
Fabry-related
symptoms
may
deteriorate
.
Diseases
Validation
Diseases presenting
"pain"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
adrenomyeloneuropathy
aniridia
aromatase deficiency
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital diaphragmatic hernia
congenital toxoplasmosis
cushing syndrome
cutaneous mastocytosis
cystinuria
dedifferentiated liposarcoma
dentin dysplasia
dracunculiasis
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
fabry disease
familial mediterranean fever
focal myositis
hirschsprung disease
hodgkin lymphoma, classical
holt-oram syndrome
junctional epidermolysis bullosa
kabuki syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
malignant atrophic papulosis
neuralgic amyotrophy
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
phenylketonuria
pleomorphic liposarcoma
primary hyperoxaluria type 1
proteus syndrome
pyomyositis
scrub typhus
sneddon syndrome
systemic capillary leak syndrome
thoracic outlet syndrome
trochlear dysplasia
typhoid
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
wolf-hirschhorn syndrome
This symptom has already been validated