Specialist Working Group for Neurology
Proposed changes to the Criteria for the clinical use of intravenous immunoglobulin in Australia, Second Edition
ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
SWG RATIONALE FOR PROPOSED CHANGE
Condition
Name
Guillain–Barré Syndrome (GBS)
Guillain–Barré Syndrome (GBS), including variants
Addition: the inclusion of variants in the title.
Variants were already included within the
condition.
Specialty
Neurology
Neurology
Chapter
5
5
Specific
Conditions
GBS
GBS
GBS variants
GBS variants
Level of
Evidence
Clear evidence of benefit (Category 1).
Clear evidence of benefit (Category 1).
Justification for
Evidence
Category
One systematic review of nine RCTs of
moderate quality found IVIg hastened
recovery in adults with GBS to the same
degree as plasma exchange (Biotext
2004).
One systematic review of nine randomised controlled
trial (RCTs) of moderate quality found intravenous
immunoglobulin (IVIg) hastened recovery in adults with
GBS to the same degree as plasma exchange (Biotext
2004).
This conclusion was confirmed in a 2014 Cochrane
review. In severe disease, IVIg started within two weeks
One low-quality RCT with a small sample
from onset hastens recovery as much as plasma
size (n=21), in which the randomisation of
exchange. Three studies, including a total of 75 children,
patients to the IVIg treatment group was
suggested that IVIg significantly hastens recovery
skewed, was identified. Children who
compared with supportive care. One low-quality RCT
received IVIg treatment showed earlier
with 21 mildly affected children showed ealier signs of
signs of improvement, and disability
This section has been updated
ITEM
Description and
Diagnostic
Criteria
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
scores were lower at four weeks than the
placebo group (Frommer and Madronio
2006).
improvement and lower disability grades after four
weeks with IVIg than supportive treatment alone.
(Frommer and Madronio 2006).
GBS is the commonest cause of acute
flaccid paralysis in the West. The
syndrome typically presents with rapidly
progressive, relatively symmetrical
ascending limb weakness consistent with
a polyradiculoneuropathy and often with
associated cranial nerve involvement.
GBS is the commonest cause of acute flaccid paralysis in
the West. The syndrome typically presents with rapidly
progressive, relatively symmetrical ascending limb
weakness consistent with a polyradiculoneuropathy and
often with associated cranial nerve involvement.
Motor signs and symptoms usually
predominate over sensory signs and
symptoms. Loss of tendon reflexes occurs
in most cases. Major complications
include respiratory failure and autonomic
dysfunction.
The disease is monophasic, reaching its
nadir usually within two weeks, although
arbitrary definition accepts a limit of four
weeks. A plateau phase of variable
duration follows the nadir before gradual
recovery. Although recovery is generally
good or complete in the majority of
patients, persistent disability has been
reported to occur in about 20% and
death in 4 to 15% of patients.
National Blood Authority
SWG RATIONALE FOR PROPOSED CHANGE
Motor signs and symptoms usually predominate over
sensory signs and symptoms. Loss of tendon reflexes
occurs in most cases. Major complications include
respiratory failure and autonomic dysfunction.
The disease is monophasic, reaching its nadir usually
within two weeks, although arbitrary definition accepts
a limit of four weeks. A plateau phase of variable
duration follows the nadir before gradual recovery.
Although recovery is generally good or complete in the
majority of patients, persistent disability has been
reported to occur in about 20% and death in 4 to 15% of
patients.
IVIg has been shown to have the same efficacy as
plasma exchange. The choice is based on availability,
practicality, convenience, cost, and ease or safety of
administration (Asia–Pacific IVIg Advisory Group).
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ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
IVIg has been shown to have the same
efficacy as plasma exchange. The choice
is based on availability, practicality,
convenience, cost, and ease or safety of
administration (Asia–Pacific IVIg Advisory
Group).
Investigations
There is no biological marker for GBS. It is diagnosed by
clinical recognition of rapidly evolving paralysis with
areflexia. Investigations include the following:

Investigations
There is no biological marker for GBS. It is
diagnosed by clinical recognition of
rapidly evolving paralysis with areflexia.
Investigations include the following:

SWG RATIONALE FOR PROPOSED CHANGE

Cerebrospinal fluid (CSF) protein
elevation, although the level may
be normal in the first two weeks
of illness. The CSF white cell
count may rise transiently, but a
sustained pleocytosis suggests an
alternative diagnosis or
association with an underlying
illness (e.g. HIV).
Cerebrospinal fluid (CSF) protein elevation,
although the level may be normal in the first
two weeks of illness. The CSF white cell count
may rise transiently, but a sustained pleocytosis
suggests an alternative diagnosis or association
with an underlying illness (e.g. HIV).
Electrophysiological studies may show changes
after the first or second week of the illness,
including conduction block, conduction slowing
or abnormalities in F waves.
Electrophysiological studies may show
changes after the first or second week of
the illness, including conduction block,
conduction slowing or abnormalities in F
waves.
Diagnosis is
required
Yes
National Blood Authority
By which
specialty
General
physician or
Yes
By which
specialty
Neurologist
SWG has recommended that diagnosis is limited
to neurologists, if Ig is to be used. This is already
pg. 3
ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
Neurologist
By which
specialty
Neurologist
(if
neurologist
did not make
original
diagnosis)
SWG RATIONALE FOR PROPOSED CHANGE
required for the second dose, and is now
extended to all eligible patients because of the
requirement for assessment against formal
neurological scoring methods.
Diagnosis must
be verified
Yes
No
By which
specialty
Exclusion
Criteria
-
-
No exclusion criteria required.
Indications
GBS and its variants with significant
disability and progression
Initial therapy for GBS with significant disability and
progression.
The addition of a second indication is required as
there is a requirement in the original Criteria for
mandatory assessment by a neurologist if a second
dose is required, (noting that a second dose is not
continuing treatment but has been created as a
new authorisation). Data will be collected on
response to initial dose.
Relapse in GBS treatment-related fluctuation with
initial improvement and subsequent deterioration
post IVIg treatment (neurologist review required).
Qualifying
Criteria
Patients with GBS (or variant) with
significant disability and disease
progression
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Initial therapy for GBS with significant disability and
progression.
SWG agreed that the GBS Disability Score be used
to assess elibility all patients except some GBS
variants with bulbar or autonomic features rather
than motor weakness. The GBS Disability Score has
pg. 4
ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
SWG RATIONALE FOR PROPOSED CHANGE
Assessment by a neurologist is
recommended. But not mandatory.
[Group 1]
been updated since the last version.
Disability Grade
0 - A healthy state
Patient with GBS demonstrates significant disability as
objectively measured by the GBS Disability Score of
greater than one point (adapted from Hughes et al
1978).
1 – Minor symptoms or signs of
neuropathy but capable of
manual work
0 - A healthy state
1 – Minor symptoms and capable of running
2 – Able to walk without the
support of a stick but incapable
of manual work
2 – Able to walk 10 metres or more without
assistance but unable to run
3 – Able to walk 10 metres across an open
space with help
3 – Able to walk with a stick,
appliance or support
4 – Bedridden or chairbound
4 – Confined to bed or chair
bound
5 – Requiring assisted ventilation for at least
part of the day
5 – Requiring assisted ventilation
6 – Dead
Qualification score is defined as > 1. Revised values
for the GBS disability score are shown opposite and
endorsed by the SWG (Lancet 1978;2:750-753).
6 – Dead
Progressive weakness is being used as a criterion to
require that disease progression has a trajectory to
significant disability. Text comments will be used to
capture this information.
Patients with GBS variants may be able to walk yet
still have significant disability and risk of
progression, not measured by GBS Disability Score.
In this instance, description of symptoms will be
used.
OR
Patient with GBS variant demonstrates bulbar or
autonomic features and significant disability.
It was noted that disease progression is difficult to
measure or set parameters for a rate, therefore a
textual description would be best way to assess.
AND
New indication
[Group 2]
The progressive nature of the weakness indicates a
trajectory to significant disability.
Relapse in GBS treatment-related fluctuation with
National Blood Authority
Evidence supports a second dose for treatmentrelated fluctuations as allowed under the current
Criteria. It was noted that the Disability Grade may
not improve even when patient has responded to
pg. 5
ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
Approximately 10% of patients relapse,
which may require a second treatment
with Ig. A second dose of IVIg must only
be on the advice of and after assessment
by a neurologist.
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
SWG RATIONALE FOR PROPOSED CHANGE
initial improvement and subsequent deterioration
post IVIg treatment (neurologist review required).
IVIg, when GBS is very severe.
The Ig request is made by a neurologist.
AND
Patient has demonstrated an Initial response
followed by recurrent weakness with no alternative
explanation as demonstrated by deterioration in a
recent Medical Research Council (MRC) Sum (12)
Score compared to the MRC Sum (12) Score post Ig
treatment (Kleyweg et al 1991).
It was agreed that deterioration would be better
measured by MRC score as it would be more
sensitive than INCAT. There is currently no data to
support a second dose of IVIg if first dose was
ineffective unless delta IgG levels are being
measured which are not widely available. Any
further deterioration would be expected to occur
within 1-2 weeks if Ig treatment. The MRC Sum
(12) Score will be used to assess and document the
deterioration.
Detail regarding the MRC Sum (12) Score
Range 0 (total paralysis) – 60 (normal strength)
Sum of 6 muscle pairs examined bilaterally:

Kleyweg, RP, van der Meché, FGA, Schmitz, PIM 1991,
‘Interobserver agreement in the assessment of muscle
strength and functional abilities in Guillain-Barré
syndrome’, Muscle Nerve, vol. 14, pp. 1103–1109.

Arm: shoulder abductors, elbow flexors,
wrist extensors
Leg: hip flexors, knee extensors, foot
dorsiflexors
MRC grade 0-5 (full numbers ie. 4+=4, 4- =3)
References to MRC Sum Score (12) are provided
and will link to a reference page containing detail
of the measurements required.
Review Criteria
Initial therapy for GBS with significant disability and
progression
Review Preamble
Given that Ig treatment for GBS is one-off, no
review will be required however, clinicians can
submit outcome data.
Review criteria for assessing the efficacy of IVIg use:
National Blood Authority
pg. 6
ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
SWG RATIONALE FOR PROPOSED CHANGE
Improvement in disability at four weeks after Ig
treatment.

GBS Disability Score + Date of Assessment
0 - A healthy state
Review
1 – Minor symptoms and capable of running
Review criteria for assessing
effectiveness of IVIg use
2 – Able to walk 10 metres or more without
assistance but unable to run i
Primary outcome measures:
3 – Able to walk 10 metres across an open
space with help
improvement in disability grade four
weeks after treatment
4 – Bedridden or chairbound
5 – Requiring assisted ventilation for at least
part of the day
Disability Grade
0 - A healthy state
1 – Minor symptoms or signs of
neuropathy but capable of
manual work
2 – Able to walk without the
support of a stick but incapable of
manual work
The updated GBS Disability Score is more detailed
in defining the disability eg defined walking
distances for assessment.
6 – Dead
OR
Improvement in bulbar or autonomic symptoms in
patient with GBS variant.
(Large Text*) & (Date) of Assessment
3 – Able to walk with a stick,
appliance or support
4 – Confined to bed or chair
bound
• Time until walking unaided
5 – Requiring assisted ventilation
• Time until recovery of walking with aid
6 – Dead
• Time until off ventilation ( for those ventilated)
Secondary outcome measures
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Optional secondary outcome measures
• Treatment-related fluctuation
pg. 7
ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
• Time until walking unaided
• Time until recovery of walking
with aid
• Time until off ventilation ( for
those ventilated)
• Treatment related fluctuation
SWG RATIONALE FOR PROPOSED CHANGE
• Death or disability
[Review Postscript]
Relapse in GBS (treatment-related fluctuation) with
recurrent weakness after initial improvement may
require a second treatment with IVIg. A second dose of
IVIg must only be on the advice of and after assessment
by a neurologist.
• Death or disability
Approximately 10% of patients relapse,
which may require a second treatment
with Ig. A second dose of IVIg must only
be on the advice of and after assessment
by a neurologist.
Relapse in GBS treatment-related fluctuation with
initial improvement and subsequent deterioration
post IVIg treatment (neurologist review required).
Review Preamble
Review criteria for assessing the efficacy of IVIg use are:
Improvement in GBS Disability Score at four weeks after
Ig treatment and date of assessment.
OR
Improvement in bulbar or autonomic symptoms in
patient with GBS variant & Date of Assessment.
Optional secondary outcome measures
• Time until walking unaided
• Time until recovery of walking with aid
• Time until off ventilation ( for those ventilated)
• Treatment-related fluctuation
National Blood Authority
pg. 8
ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
SWG RATIONALE FOR PROPOSED CHANGE
• Death or disability
[Review Postscript]
Relapse in GBS (treatment-related fluctuation) with
recurrent weakness after initial improvement may
require a second treatment with IVIg. A second dose of
IVIg must only be on the advice of, and after
assessment by, a neurologist.
Dose
Induction - 2 g/kg in 2 to 5 divided doses.
Initial therapy for GBS with significant disability and
progression.
The dosing approach is the same for both
indications.
Induction dose is unchanged.
Aim for minimum dose to maintain
optimal functional status.
Refer to the current product information
sheet for further information.
The aim should be to use the lowest
dose possible that achieves the
appropriate clinical outcome for each
patient.
Initial - 2 g/kg in 2 to 5 divided doses.
System Controls for Dosing
The amount per dose should be titrated to the
Individual’s response.
Refer to the current product information sheet for
further information.
This script was deleted as inappropriate for this
condition - the dose is standard for all patients (
unless lean body mass is being used).
Relapse in GBS with significant disability and
progression post IVIg treatment (neurologist review
required)
National Blood Authority
pg. 9
ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
SWG RATIONALE FOR PROPOSED CHANGE
Initial - 2 g/kg in 2 to 5 divided doses.
Refer to the current product information sheet for
further information.
As above - standard dosing applies.
POTENTIAL OPERATIONAL IMPACT
Diagnosis and Ig ordering can only be made by a neurologist so this will require the referral of patients where initial care is being provided by General Physicians.
Request for authorisation for a second dose of Ig can only be made by a neurologist under current Criteria requiring the referral of patients where initial care is being
provided by General Physicians. This will now be required for any Ig treatment.
POTENTIAL IMPACT ON DEMAND
Patient numbers in
2013-14
Usage 2013-14
663 patients treated
Some potential for reduction in use by:

3%

System requirement for moderate to severe
level of disease severity at qualifying (cease
use in mild cases that was reported during
IVIg Review)
No impact on demand is expected due to GBS
variants but improved data will be available
regarding clinical outcome for future analysis.
Given that these changes effect up to 3% usage, the
savings estimate is minor.
POTENTIAL COST
Cost
Anticipated reduction in cost, if any
Minor
Marginal = borderline or unchanged from current cost
Minor = decrease by $500K - $1.99M from current cost
Major = decrease $2M+ from current cost
BIBLIOGRAPHY
Association of British Neurologists 2005, Guidelines for the use of intravenous immunoglobulin in neurological diseases, The Association, London. Available from:
National Blood Authority
pg. 10
www.theabn.org/ documents/IVIg-Guidelines-2005.pdf [cited 7 Dec 2007]
Biotext 2004, ‘Summary data on conditions and papers’, in A systematic literature review and report on the efficacy of intravenous immunoglobulin therapy and its risks,
commissioned by the National Blood Authority on behalf of all Australian Governments, pp.149–50. Available from: http://www.nba.gov.au/pubs/pdf/report-lit-rev.pdf.
Frommer, M & Madronio, C 2006, The use of intravenous immunoglobulin in Australia. A report for the National Blood Authority, Part B: systematic literature review, Sydney
Health Projects Group, University of Sydney, Sydney, pp. 32–4.
Hughes, RAC, Raphaël, J-C, Swan, AV, et al 2006, ‘Intravenous immunoglobulin for Guillain Barré syndrome (Cochrane Review)’, in The Cochrane Library, Issue 1, John Wiley
& Sons, Ltd, Chichester, UK.
Kleyweg, RP, van der Meché, FGA, Schmitz, PIM 1991, ‘Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barré syndrome’,
Muscle Nerve, vol. 14, pp. 1103–1109.
Korinthenberg, R, Schessl, J, Kirschner, J, et al 2005, 'Intravenously administered immunoglobulin in the treatment of childhood Guillain-Barré syndrome: a randomized trial’,
Paediatrics, vol. 116, no. 1, pp. 8–14.
Kornberg, AJ, for the Asia–Pacific IVIg Advisory Board 2004, Bringing consensus to the use of IVIg in neurology. Expert consensus statements on the use of IVIg in neurology,
1st edn, Asia–Pacific IVIg Advisory Board, Melbourne, pp. 14–20.
END OF DOCUMENT
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pg. 11