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).
pg. 2
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 or General
Physician
No change.
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)
SWG RATIONALE FOR PROPOSED CHANGE
Neurologist
Diagnosis must
be verified
Yes
By which
specialty
Neurologist
(if
neurologist
did not make
original
diagnosis)
No
By which
specialty
Neurologist must be
consulted for 2nd dose.
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
Assessment by a neurologist is
recommended. But not mandatory.
Disability Grade
0 - A healthy state
National Blood Authority
Initial therapy for GBS with significant disability and
progression.
[Group 1]
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).
OR
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 been updated since
the last version:
0 - A healthy state
1 – Minor symptoms and capable of
pg. 4
ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
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
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
Patient with GBS variant demonstrates bulbar or
autonomic features and significant disability
AND
[Group 2]
The progressive nature of the weakness indicates a
trajectory to significant disability.
3 – Able to walk with a stick,
appliance or support
4 – Confined to bed or chair
bound
5 – Requiring assisted ventilation
6 – Dead
Relapse in GBS treatment-related fluctuation with
initial improvement and subsequent deterioration
post IVIg treatment (neurologist review required).
The Ig request is made by a neurologist or neurologist
has been consulted (including by teleconference) and
has approved a second dose
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).
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.
National Blood Authority
running
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
4 – Bedridden or chairbound
AND
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
SWG RATIONALE FOR PROPOSED CHANGE
5 – Requiring assisted ventilation for
at least part of the day
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).
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.
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.
pg. 5
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)
by a neurologist.
SWG RATIONALE FOR PROPOSED CHANGE
New indication
Evidence supports a second dose for
treatment-related fluctuations as allowed
under the current Criteria. It was noted that
the Disability Grade may not improve even
when patient has responded to IVIg, when
GBS is very severe.
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.
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 is not mandated for this indication however the
following criteria may be useful in assessing the
effectiveness of therapy.

National Blood Authority
Given that Ig treatment for GBS is one-off,
no review will be required however,
clinicians can submit outcome data.
Improvement in disability at four weeks after Ig
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
treatment.
Improvement in bulbar or autonomic symptoms
in patient with GBS variant.
Optional secondary outcome measures
Review
• Time until walking unaided
Review criteria for assessing
effectiveness of IVIg use
• Time until recovery of walking with aid
Primary outcome measures:
• Time until off ventilation ( for those ventilated)
• Treatment-related fluctuation
improvement in disability grade four
weeks after treatment
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
3 – Able to walk with a stick,
appliance or support
4 – Confined to bed or chair
bound
5 – Requiring assisted ventilation
• Death or disability
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.
Relapse in GBS - treatment-related fluctuation - with
initial improvement and subsequent deterioration
post IVIg treatment (neurologist review required).
Review is not mandated for this indication however the
following criteria may be useful in assessing the
effectiveness of therapy.

Improvement in GBS Disability Score at four
weeks after Ig treatment

Improvement in bulbar or autonomic symptoms
in patient with GBS variant.
6 – Dead
Secondary outcome measures
• Time until walking unaided
National Blood Authority
The updated GBS Disability Score is more
detailed in defining the disability eg defined
walking distances for assessment.
pg. 7
ITEM
CRITERIA FOR THE CLINICAL USE OF
INTRAVENOUS IMMUNOGLOBULIN IN
AUSTRALIA, SECOND EDITION (CRITERIA)
• Time until recovery of walking
with aid
• Time until off ventilation ( for
those ventilated)
• Treatment related fluctuation
• Death or disability
PROPOSED REVISIONS TO THE CRITERIA (INCLUDING
ADAPTATION TO THE IG SYSTEM)
SWG RATIONALE FOR PROPOSED CHANGE
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
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.
Dose
Induction - 2 g/kg in 2 to 5 divided doses.
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.
• Death or disability
Initial therapy for GBS with significant disability and
progression.
The dosing approach is the same for both
indications.
Induction dose is unchanged.
Initial - 2 g/kg in 2 to 5 divided doses.
Refer to the current product information sheet for
further information.
Relapse in GBS with significant disability and
progression post IVIg treatment (neurologist review
required)
This script regarding using minimal dose was
deleted as inappropriate for this condition the dose is standard for all patients ( unless
lean body mass is being used).
As above - standard dosing applies.
Initial - 2 g/kg in 2 to 5 divided doses.
Refer to the current product information sheet for
further information.
National Blood Authority
pg. 8
BIBLIOGRAPHY
Association of British Neurologists 2005, Guidelines for the use of intravenous immunoglobulin in neurological diseases, The Association, London. Available from:
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