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Colchicine failure in familial Mediterranean fever and potential alternatives: embarking on the anakinra trial.
[familial mediterranean fever]
Familial
Mediterranean
fever
(
FMF
)
is
a
genetic
auto-
inflammatory
disease
characterized
by
spontaneous
short
attacks
of
fever
,
elevated
acute
-phase
reactants
,
and
serositis
.
Approximately
5
%
-
10
%
of
FMF
patients
do
not
respond
to
colchicine
treatment
and
another
5
%
are
intolerant
to
colchicine
because
of
side
effects
.
Recently
,
following
the
discovery
of
the
inflammasome
and
recognition
of
the
importance
of
interleukin-
1
beta
(
IL
-
1
beta
)
as
the
major
cytokine
involved
in
the
pathogenesis
of
FMF
,
IL
-
1
beta
blockade
has
been
suggested
and
tried
sporadically
to
treat
FMF
,
with
good
results
.
To
date
,
case
reports
and
small
case
series
involving
colchicine-resistant
FMF
patients
and
showing
high
efficacy
of
IL
-
1
beta
blockade
have
been
reported
.
At
the
Israel
Center
for
FMF
at
the
Sheba
Medical
Centerthe
first
double
-blind
randomized
placebo-controlled
trial
of
anakinra
in
FMF
patients
who
are
resistant
or
intolerant
to
colchicines
is
underway
.
In
this
report
we
discuss
the
mechanism
of
colchicine
resistance
in
FMF
patients
,
the
data
in
the
literature
on
IL
1
beta
blockade
in
these
patients
,
and
the
anakinra
trial
inclusion
criteria
and
study
protocol
.