Table Of ContentPaed-006: The use of corticosteroids in juvenile idiopathic arthritis (JIA)
FEEDBACK FOLLOWING PRELIMINARY SEARCH
QUERY
REF:
Paed-‐006
Received:
1st
December
2014
Feedback
to
CSG:
10th
January
2015
(due),
7th
January
2015
(sent)
SEARCH METHODOLOGY
The
content
of
this
feedback
report
refers
only
to
the
most
relevant
material
located
under
each
of
the
evidence
headings
and
is
drawn
predominantly
from
author
abstracts
or
research
recommendations
within
guidelines.
The
question
is
posed
in
the
context
of
the
use
corticosteroids
for
remission
induction
or
treatment
of
children
in
juvenile
idiopathic
arthritis
(JIA).
Further
details
of
all
the
studies
included
in
this
report
are
shown
in
the
appendix,
sorted
by
report
section
and
author
name.
Criteria used (PICO):
Who? (population)
Children
with
juvenile
idiopathic
arthritis
What? (intervention/exposure/measure)
Corticosteroids
Comparison
N/A
What is measured? What are the outcomes?
Remission,
reduction
in
disease
activity,
JIA
core
outcomes,
juvenile
arthritis
disease
activity
score
(JADAS)
Location and setting
Any
Exclusion Criteria
Non-‐English
language
guidelines,
recommendations,
systematic
reviews,
overviews
and
clinical
opinions.
However,
non-‐English
language
primary
research
articles
with
English
abstracts
were
included
if
relevant,
see
Section
D:
Primary
Research.
Conference
abstracts
were
only
included
in
feedback,
where
no
peer-‐reviewed
article
was
available.
P age 1
Databases Searched
CINAHL;
Cochrane
Library;
EMBASE;
MEDLINE;
ISRCTN
Register;
UK
Clinical
Research
Network
Study
Portfolio;
NIH
records
on
ClinicalTrials.gov;
Nederlands
Trial
Register;
German
Clinical
Trials
Register;
Australian
New
Zealand
Clinical
Trials
Registry;
World
Health
Organization
(WHO):
International
Clinical
Trials
Registry.
Types of Study
Clinical
trials;
Observational
studies
Keywords searched
Search
protocols
were
designed
around
the
following
terms:
juvenile
(idiopathic)
arthritis
AND
steroids
(e.g.
see
Appendix
1
for
MEDLINE
protocol)
Date limits
Last
5
years
i.e.
2009-‐2014.
Summary of available evidence
EVIDENCE
TYPE
INCLUDED
IN
FEEDBACK
A
Evidence
Summaries
10
(11
papers)
B
Systematic
Reviews
&
Meta-‐analyses
12
C
Clinical
Trial
Registries
(Current
and
Closed)
0
D
Primary
Research
85
studies
(91
articles)
E
Overviews
and
expert
opinions
n/a
F
Intellectual
Property
Office
n/a
Note:
where
abstracts
refer
to
depomedrone
and/or
methyl
prednisolone
these
drugs
have
been
highlighted
using
italics
and
bold
fonts.
RESULTS
A: Good Quality Evidence Summaries (including guidelines)
See
Appendix
2,
Section
A
for
details
of
reviews
included
in
this
section.
Ten
guidelines
and/or
consensus
statements
(11
papers)
were
identified
as
pertinent
to
this
evidence
review.
• Seven
evidence
summaries
(8
papers)
addressed
the
general
treatment
of
JIA
(Beukelman,
et
al.
2011;
DeWitt,
et
al.
2012;
Dueckers,
et
al.
2012;
Munro,
et
al.
2014;
Ringold,
et
al.
2014;
The
Royal
Australian
College
of
General
Practitioners,
2009),
Page 2
including
tuberculosis
screening
for
children
with
JIA
on
biologic
medication
(Ringold,
et
al.
2013a
&
b);
• One
guideline
specifically
addressed
uveitis
associated
with
JIA
(Heiligenhaus,
et
al.
2012);
• And
another,
the
use
of
methyl-‐prednisolone
in
paediatric
rheumatology
(BSPAR,
2011).
In
general
these
evidence
summaries
identify
a
paucity
of
evidence
regarding
the
use
of
systemic
steroids
e.g.
Beukelman,
et
al.
(2011)
conclude
there
is
a
“near
complete
lack
of
published
evidence”
(page
14)
for
the
use
of
systemic
glucocorticoids,
whilst
Dueckers,
et
al.
(2012)
state
“There
are
no
controlled
trials
and
no
standardized
therapeutic
regimes
for
the
use
of
systemic
GC”
(page
180).
In
contrast,
there
appears
to
be
reasoable
quality
studies
to
support
the
use
of
intraarticular
injections
in
JIA,
leading
to
Grade
A
recommendations
for
use.
In
the
case
of
JIA-‐associated
uveitis
other
forms
of
steroids
are
also
considered:
Heiligenhaus,
et
al.
(2012)
report
there
is
high
quality
evidence
for
the
use
of
topical
steroids,
with
low
quality
evidence
for
intravitreal
injections.
B: Systematic Reviews and Meta-analyses
See
Appendix
2,
Section
B
for
details
of
reviews
included
in
this
section.
Twelve
systematic
reviews
(SRs)
were
identified
for
this
evidence
review.
• Eight
SRs
addressed
the
use
of
intraarticular
steroid
injections:
o Four
SRs
in
JIA
(Bloom,
Alario
and
Miller,
2011;
Gotte,
2009)
specifically
affecting
the
lower
limb
(Jennings,
Hennessy
and
Hendry,
2014)
and
temporomandibular
joint
(Stoustrup,
et
al.
2013);
o Four
SRs
across
a
broader
range
of
conditions
including
OA,
RA
and
JIA
(Garg
ad
Deodhar,
2013
[conference
abstract];
Habib
2009;
Habib,
Saliba
and
Nashashibi,
2010;
Scherer,
Rainsford,
Kean
and
Kean,
2014);
• Two
SRs
(possibly
related)
examine
the
DMARDs,
compared
to
conventional
treatment
i.e.
NSAIDs
and/or
intraarticular
corticosteroids,
in
children
with
JIA
(Kemper,
et
al.
2011;
Kemper,
van
Mater,
Coeytaux,
Williams
and
Sanders,
2012).
• Two
SRs
focus
on
uveitis,
of
which
one
includes
(Pilly,
Health,
Tschuor,
Lightman
and
Gale,
2013)
and
the
other
specifically
addresses
JIA-‐associated
uveitis
(Heiligenhaus,
2014
[conference
abstract]);
In
the
case
of
intraarticular
steroid
injections,
there
appears
to
be
reasonable
evidence
to
suggest
it
is
a
safe
and
effective
treatment
for
JIA.
There
is
also
some
indication
that
triamcinolone
hexacetonide
may
have
greater
efficacy
and/or
onset
of
action
compared
to
other
corticosteroids.
C: Clinical Trial Registries
No
clinical
trials
were
identified
for
this
report.
Page 3
D: Primary Research
See
Appendix
2,
Section
D
for
details
of
studies
included
in
this
section.
Ninety-‐one
primary
research
articles,
reporting
85
studies
were
identified
for
this
review,
including
4
intervention
studies
(5
articles),
12
prospective
observational
studies
(13
articles),
4
cross-‐sectional
observation
studies
(5
articles),
59
retrospective
observational
studies
(61
articles)
and
6
unclear
observational
studies
(7
articles).
Intervention
studies
See
Appendix
2,
Section
D.1
for
details
of
studies
included
in
this
section.
Four
interventions
studies,
5
publications,
were
identified
for
this
evidence
review;
all
involved
the
use
of
intra-‐articular
steroid
injections:
• RCT
with
active
control
o with
or
without
methotrexate
in
oligoarticular
JIA
(Bracciolini,
et
al.,
2014)
[conference
abstract]
o in
the
temporomandibular
joint
in
children
with
JIA
(Olsen-‐Bergem
and
Bjornland,
2010;
2014)
• Uncontrolled
feasibility
study
o Efficacy
(Verma,
Gupta,
Lodha
and
Kabra,
2009)
and
effect
on
isokinetic
muscle
strength
(McKay,
Ostring,
Broderick,
Chaitow
and
Singh-‐Grewal,
2013)
Observational
studies
See
Appendix
2,
Section
D.2
for
details
of
studies
included
in
this
section.
Eighty
one
observational
studies,
reported
in
86
papers,
were
pertinent
to
this
evidence
review.
These
have
been
subdivided
according
to
whether
the
studies
were
prospective
(12
studies),
retrospective
(59
studies),
cross-‐sectional
(4
studies)
or
unclear
(6
studies).
Prospective
Twelve
prospective
observational
studies,
in
13
papers,
were
identified.
• Two
studies
examined
the
current
management
of
JIA
including
use
of
oral
steroids
e.g.
low-‐dose
prednisolone
(Oen,
et
al.
2010;
Shen,
Yao,
Yeh
and
Huang,
2013);
• Ten
studies,
11
articles,
focused
on
intra-‐articular
injections:
o In
children
with
JIA
(Carrasco,
et
al.,
2014
[conference
abstract];
Mrazik
and
Vargova,
2013;
Rintamaki,
et
al.,
2011)
including
particularly
oligoarticular
JIA
(Barsalou,
et
al.,
2011
[conference
abstract])
o Specifically
of
the
ankle
(Laurell,
et
al.,
2011),
wrist
(Laurell,
et
al.,
2012)
and
TMJ
(Martini,
Fusetti,
Vittadello,
Buccella
and
Zulian,
2011
[conference
abstract])
in
JIA
o Use
of
‘Doctors-‐medical
clowns’
in
nitrous
oxide
sedation
for
intra-‐articular
injections
in
JIA
(Uziel,
et
al.,
2013;
2014
[conference
abstract])
Page 4
o The
effect
of
RANTES
polymorphism
on
clinical
response
to
intraarticular
triamcinolone
injection
in
juvenile
rheumatoid
arthritis
(Yao,
Tsai
and
Huang,
2009);
o And
responsiveness
of
the
Juvenile
Arthritis
Foot
disability
Index
(Esbjornsson,
Iversen,
Brostrom,
Hagelberg
and
Andre,
2013
[conference
abstract]).
Retrospective
Fifty
nine
retrospective
observational
studies,
across
61
papers,
were
identified.
• Thirty
eight
studies,
in
40
articles,
focused
on
intraarticular
steroid
injections,
as
follows:
o Role
of
IA
injections
in
the
management
of
JIA
(Akikusa,
Munro,
Buckle
and
Allen,
2013;
James,
et
al.,
2014
[conference
abstract];
Papadopoulou,
et
al.,
2013),
along
with
tendon
sheath
injections
(Messia,
Marafon,
De
Benedetti
and
Magni-‐Manzoni,
2014
[conference
abstract])
o Efficacy
including
probability
of
sustained
remission
following
single
and
multiple
steroid
joint
injection
in
JIA
(de
Oliveria
Sato,
et
al.,
2014;
Lanni,
et
al.
2011;
2013
[conference
abstract];
Leow,
et
al.,
2014;
Melo,
Dias
and
Brito,
2010
[conference
abstract];
Sato,
Fernandes,
Nascimento,
Brito
and
Saad-‐Magalhaes,
2011
[conference
abstract];
Srinivasan,
et
al.,
2011
[conference
abstract];
Stefan,
et
al.,
2011
[conference
abstract];
Trigilia,
et
al.,
2011
[conference
abstract])
o Dosing
schedule
in
juvenile
arthritis
(Eberhard,
Ilowite
and
Sison,
2012)
o Specifically
for
children
with
JIA
with
the
following
joints
affected:
Elbow
(Marino,
et
al.,
2012)
Knee
joint
(Pastore,
Crocco,
Taddio
and
Lepore,
2011)
Ankle
(Proulx-‐Gauthier,
LeBlanc
and
Chedeville,
2014
[conference
abstract]),
aswell
as
the
wrist
(Jadhav
and
Kan,
2014;
Kan
and
Graham,
2011)
Temporomandibular
joint
(Davidson,
Santere,
Krisjane,
Urtane
and
Stanevica,
2013;
Groh
and
Tashima,
2014
[conference
abstract];
Habibi,
Ellis,
Strike
and
Ramanan,
2012;
Lochbuhler,
Sauernmann,
Muller
and
Kellenberger,
2013;
Sharpe,
Good,
Beukelman,
Waite
and
Cron,
2010
[conference
abstract];
Smith
and
Friswell,
2011
[conference
abstract];
Stoll,
et
al.,
2012)
Including
use
of
early
TMJ
MRI
and
its
effect
on
treatment
including
IA
injection
(Hauser,
et
al.
2014;
Saurenmann,
et
al.,
2011
[conference
abstract])
Specifically
US
guided
IA
injections
(Parra,
et
al.,
2010)
Hip
joint,
using
US
guided
injections
(Agarwal,
Kavirayani,
Ramanan
and
Ellis,
2012
[conference
abstract])
Sacroiliac
joint
for
refractory
enthesitis-‐related
arthritis
in
children
(Fritz,
et
al.
2011)
o Use
of
ultrasound
of
knee
and
ankle
in
JIA
including
response
to
IA
steroid
injections
(Trinh,
et
al.,
2010
[conference
abstract]).
Page 5
o Use
of
MRI
prior
to
wrist
injection
in
children
with
JIA
(Davis,
Kan
and
Brent
Graham,
2011
[conference
abstract])
o Ultrasound
guided
percutaneous
joint,
tendon
sheath
(Young,
et
al.,
2012)
and
bursal
corticosteroid
injections
in
children
with
JIA
(Shiels,
et
al.,
2010
[conference
abstract]).
o Use
of
dream-‐doctors/medical
clowns
for
children
with
JIA
undergoing
intra-‐articular
injection
procedures
(Oren-‐Ziv,
Hanuka,
Rotchild,
Gluzman
and
Uziel,
2012)
o Use
of
nitrous
oxide
analgesia
for
intraartricular
steroid
injections
in
children
with
JIA
(Chan,
Wyllie
and
Foster,
2012;
2013
[conference
abstracts])
o Targeted
corticosteroid
injection
into
the
deep
infrapatellar
bursa
in
children
with
deep
infrapatellar
bursitis
assocated
with
JIA
(Alqanatish,
et
al.,
2011)
o Arthroscopy
of
TMJ
in
children
with
JIA
including
steroid
injection
(Kinard,
Bouloux,
Abramowicz
and
Prahalad,
2014
[conference
abstract]).
• Eleven
studies
reported
on
other
forms
of
steroid
treatment
for
JIA
and
associated
conditions:
o General
management
of
systemic
onset
JIA
including
oral
glucocorticoids
(Jariwala,
Agarwal,
Kumar
and
Sawhney,
2013)
o Oral
corticoid
treatment
for
systemic
JIA
or
Still’s
disease
(Lord,
Allaoua
and
Ratib,
2011)
o Management
of
a
case
of
refractory
systemic
JIA
including
oral
and
intravenous
steroids
(Mellos,
et
al.,
2014
[conference
abstract])
o Dexamethasone
iontophoresis
for
temporomandibular
joint
involvement
in
JIA
(Mina,
et
al.,
2011)
o Management
of
JIA-‐associated
uveitis
including
use
of
topical
medicaions
and
systemic
glucocorticoid
therapy
(Marvillet,
et
al.,
2009;
Nouar,
Hoarau,
Uettwiller
and
Lez,
2014)
o Case
of
cricoarytenoid
arthritis
–
methylprednisolone
followed
by
maintenance
oral
steroids
(Ladak,
Abbas,
Harrison,
Davis
and
McDongah,
2014
[conference
abstract])
o Intravitreal
implant
for
JIA-‐associated
uveitis
(Serafino,
et
al.,
2014
[conference
abstract]);
paediatric
uveitis
including
uveitis
associated
with
JIA
(Bratton,
He
and
Weakley,
2014;
Cordero-‐Coma,
et
al.,
2013)
cystoid
macular
oedema
associated
with
JIA
(Totan,
et
al.,
2014)
• Ten
retrospective
observational
studies,
reporting
cases
of
Macrophage
activation
syndrome
(MAS)
in
JIA:
o Steroids
used
in
the
treatment
of
MAS
(Choudhary,
Berwal,
Khichar
and
Baid,
2014;
Hollister,
Umer
ad
Casillas,
2012
[conference
abstract];
Lazarevic
and
Vojinovic,
2013
[conference
abstract];
Lin,
et
al.,
2012;
Minoia,
et
al.,
2014;
Reddy,
Bhatia,
Scott
and
Page 6
Nagarajan,
2013;
Singh,
et
al.,
2012;
Vishwanath,
Krishnamurthy,
Karyampudi
and
Dutta,
2010)
o where
management
failed
and
resulted
in
death
(Juneji,
Jain
and
Mishra,
2009)
o which
occurred
during
treatment
for
systemic
onset
JIA
(Kumar
and
Rajam,
2011)
Cross-‐sectional
Four
cross-‐sectional
studies,
in
5
articles,
all
reported
on
intraarticular
injections:
• In
the
treatment
of
temporomandibular
joint
involvement
in
JIA
(Foeldvari,
Tzaribachev
and
Cron,
2014)
• The
use
of
sedation
(Casado,
et
al.,
2013)
and
anaesthesia
(Weiss,
Uribe,
Malleson
and
Kimura,
2010)
in
intraarticular
injection
or
children
with
JIA
• Survey
regarding
nurses
giving
intraarticular
steroid
injections
to
children
with
JIA
(Lee,
Hawley,
Edgerton
and
Al-‐Obaidi,
2013;
2014
[conference
abstracts])
Unclear
For
six
studies,
in
7
papers,
it
was
unclear
whether
the
study
had
been
carried
out
prospectively
or
retrospectively.
All
six
studies
were
conference
abstracts
and
were
concerned
with
IA
steroid
injections,
namely:
• Effect
of
IA
triamcinolone
hexacetonide
in
JIA
(Miotto
e
Silva,
et
al.,
2014)
• IA
steroid
injection
into
TMJ
(Saurenmann,
et
al.,
2009).
• US
guided
ankle
injections,
including
triamcinolone
and
depomedrone
(Savage,
Pascoli,
McAllister
and
Rooney,
2012
[conference
abstract];
Savage,
Pascoli
and
Rooney,
2011)
• 3D/4D
power
Doppler
sonography
of
knee
joint
in
JIA
to
determine
response
to
IA
steroid
or
infliximab
injection
(Harjacek,
Lamot,
Vidovic,
Perica
and
Bukovac,
2014)
• Analgesia
for
IA
steroid
injections
in
JIA
in
the
form
of
nitrous
oxide
(Pastore,
Moressa,
Gortani
and
Lepore,
2013)
and
as
a
Fentanyl
lollipop
(Zareen,
Finn
and
Killeen,
2011)
E: Overviews and Expert Opinions
Not
relevant
to
this
report.
F: Intellectual Property Office
Not
relevant
to
this
report.
Additional articles of interest
Whilst
not
the
main
focus
of
this
evidence
review,
a
number
of
papers
reported
on
side
effects,
adverse
effects
and
associations
with
steroid
treat,
others
on
remission
and
steroid
use
in
general:
these
have
been
listed
in
Appendix
3.
Page 7
CONCLUSION
Primary
research
comprises
the
majority
of
evidence
included
in
this
report
(85/107;
79.4%)
with
no
clinical
trials
on-‐going
or
recently
completed
and
unpublished
identified.
Observational
studies
represented
95.3%
(81/85)
of
the
primary
research,
of
which
59
studies
were
retrospective.
Only
four
intervention
studies
were
found,
all
concerned
intraarticular
steroid
injections:
two
were
RCTs
with
active
controls
and
two
uncontrolled
studies.
Furthermore,
10
guidelines/consensus
statements
and
12
systematic
reviews
were
pertinent
to
this
review.
Overall,
this
report
identifies
a
large
body
of
observational
studies
regarding
the
use
of
intraarticular
steroid
injections
in
the
treatment
of
paediatric
JIA,
in
addition
four
intervention
studies
were
found:
two
controlled
and
two
uncontrolled.
In
contrast
no
intervention
studies
and
only
13
observational
studies
were
identified
for
other
forms
of
steroid
treatment.
These
findings
concur
with
those
reported
in
the
systematic
reviews
and
consensus
statements
included
in
this
evidence
review.
In
general,
it
appears
that
there
is
a
good
body
of
reasonable
quality
evidence
for
the
use
of
IA
steroid
injections
in
paediatric
JIA
leading
to
Grade
A
recommendations
for
use,
whilst
in
contrast
there
is
a
dearth
of
research
into
the
use
of
other
forms
of
steroid
treatment
e.g.
systemic
and
topical.
Given
the
paucity
of
well-‐designed
(randomized)
controlled
trials
to
substantiate
the
effectiveness
of
corticosteroids
in
the
treatment
of
JIA,
future
trials
are
warrented.
Abbreviations
GC
Glucocorticoids
IA
Intraarticular
JIA
Juvenile
idiopathic
arthritis
MAS
Macrophage
activation
syndrome
OA
Osteoarthritis
RA
Rheumatoid
arthritis
SR
Systematic
review
TMJ
Temporomandibular
joint
US
Ultrasound
Page 8
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