Practice Parameter: Immunotherapy for GuillainBarr syndrome

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Practice Parameter Immunotherapy for
Guillain-Barré syndrome

• A report of the Quality Standards Subcommittee
  (QSS) of the American Academy of Neurology
• RAC Hughes, MD EFM Wijdicks, MD R Barohn, MD E
  Benson, DR Cornblath, MD AF Hahn, MD JM
  Meythaler, MD
• RG Miller, MD JT Sladky JC Stevens, MD
• Published in Neurology 200361736-740.

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Objective of the guideline

• To provide an evidence-based statement to guide
  physicians in the management of Guillain-Barré
  syndrome (GBS).

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Methods of evidence review

• MEDLINE search from 1966 and the Cochrane library
  (March 2002).
• Polyradiculoneuritis limited by human and
  cross referenced with therapy.
• Search results were reviewed by at least two
  members of the GBS practice parameter group.
• Recommendations were graded according to the
  levels established by the AANs Quality Standards
  Subcommittee (QSS).

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AANs Class of evidence for therapy
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AANs Recommendation Levels
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Introduction

• Prevalence
• GBS affects between one and four per 100,000 of
• the worlds population annually.
• Economic Impact
• The costs in the US have been estimated as
  110,000 for direct health care and 360,000 in
  lost productivity per patient.

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Introduction

• Health Outcomes
• Respiratory failure requiring ventilation in
• about 25 of patients with GBS
• Death in 4 to 15 of GBS patients
• Persistent disability in about 20 patients with
  GBS
• Persistent fatigue in 67 of patients with
• GBS

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• Question 1
• Does initial immunotherapy hasten recovery from
  GBS symptoms?

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Diagnostic criteria

• In most studies, the primary outcome measure
• used disability scale, where
• 0 normal
• 1 symptoms but able to run
• 2 unable to run
• 3 unable to walk unaided
• 4 bed-bound
• 5 needing ventilation
• 6 dead
• Most studies included patients with severe
  disease,
• at least grade 3 on that scale.

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Analysis of the evidence

• Plasma Exchange
• Cochrane review obtained data from six Class II
  trials comparing plasma exchange (PE) alone to
  supportive care
• The PE regimens involved exchanging about one
  plasma volume on five separate occasions spaced
  out over one to two weeks
• One trial which used two plasma volume exchanges
  on alternate days for a total of four exchanges

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Analysis of the evidence
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Analysis of the evidence
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Analysis of the evidence
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Analysis of the evidence
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Analysis of the evidence
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Conclusions

• Plasma exchange hastens recovery in non-ambulant
  patients with GBS who present within four weeks
  from the onset of neuropathic symptoms (Class II
  evidence).
• Plasma exchange also hastens recovery in ambulant
  patients who present within two weeks but the
  evidence is limited to one trial (Class II
  evidence).
• The effects of plasma exchange and IVIg are
  equivalent in patients requiring aid to
  walk(Class I evidence).
• Treatment with CSF filtration has not been
  adequately tested (Limited Class II evidence).

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Recommendations

• PE is recommended in non-ambulant patients
• within four weeks from onset (Level A, Class II
• evidence).
• PE is recommended for ambulant patients within
  two weeks from onset (Level B, limited Class II
  evidence).

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Analysis of the evidence

• IV Immunoglobulin
• Three trials compared IVIg with PE. The mean
  improvement in disability grade four weeks after
  randomization was available.
• In one Class III trial comparing IVIg with
  supportive treatment, seven of nine children who
  received IVIg recovered completely by four weeks
  compared with two of nine untreated.
• Cochrane systematic review found no trials
  comparing IV immunoglobulin (IVIg) with placebo.

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Analysis of the evidence
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Analysis of the evidence
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Analysis of the evidence
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Conclusions

• Intravenous immunoglobulin has not been
  adequately compared with placebo (limited Class
  II evidence).
• Such comparison is not now needed because, when
  started within two weeks from the onset, IVIg has
  equivalent efficacy to PE in hastening recovery
  from patients with GBS who require aid to walk
  (Class I evidence).
• Multiple complications were significantly less
  frequent with IVIg than with PE (Class I
  evidence).
• There is no evidence concerning the relative
  efficacy of PE and IVIg in patients with axonal
  forms of GBS.

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Recommendations

• IVIg is recommended for patients with GBS who
  require aid to walk within two (Level A
  recommendation) or four weeks from the onset of
  neuropathic symptoms (Level B recommendation
  derived from Class II evidence concerning PE
  started within the first four weeks).
• The effects of IVIg and plasma exchange are
  equivalent. (Level B recommendation Class I
  evidence concerning the comparisons between PE
  and IVIg started within the first two weeks).

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Analysis of the evidence

• Combination treatments
• One Class I trial showed that PE followed by IVIg
  showed no significant benefit compared with PE
  alone in any measured outcome.

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Analysis of evidence
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Analysis of evidence
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Conclusions

• Sequential treatment with PE followed by IVIg
  does not have a superior effect to either
  treatment given alone (Class I evidence).
• Sequential treatment with immunoabsorption
  followed by IVIg has not been adequately tested
  (Limited Class IV evidence).

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Recommendations

• Sequential treatment with PE followed by IVIg is
  not recommended (Level A recommendation, Class I
  evidence).
• Immunoabsorption followed by IVIg is not
  recommended (Level U recommendation, Class IV
  evidence).

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Analysis of the evidence

• Immunoabsorption
• An alternative technique to PE, which removes
  immunoglobulins.
• Has the advantage of not requiring the use of a
  human blood product as a replacement fluid.
• In a prospective trial there were no differences
  in outcome between 11 patients treated with PE
  and 13 treated with immunoabsorption

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Conclusion

• There is only limited Class IV evidence from a
  single small non-randomized, unblinded study.
•  

Recommendation

• The evidence is insufficient to recommend the use
  of immunoabsorption (Level U recommendation,
  Class IV evidence).

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Analysis of the evidence

• Steroids
• Cochrane systematic review sought all trials of
  any form of corticosteroid or adrenocorticotrophic
  hormone treatment for GBS. Six randomized trials
  were identified.
• The corticosteroid regimens included
  intramuscular ACTH, intravenous
  methylprednisolone,oral prednisolone, or
  prednisone.
• The primary outcome measure in the systematic
  review was the improvement in disability grade
  four weeks after randomization.

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Analysis of evidence
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Analysis of evidence
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Analysis of evidence
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Analysis of evidence
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Conclusion

• The combined evidence from all trials shows no
  benefit from corticosteroids (Class I evidence).
• The results of a trial of the combination of
  intravenous methylprednisolone and IVIg are
  awaited.

Recommendation

• Corticosteroids are not recommended in the
  treatment of GBS (Level A, Class I evidence).

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• Question 2
• Are there special issues in the management of
  children with GBS?

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Analysis of the evidence

• GBS in Children
• The clinical features of GBS in children are
  similar to those in adults except that severe
  conditions are less common and axonal forms of
  the disease are more frequent in some
  populations.
• In younger children, in particular, pain is
  frequently the only symptom they are able to
  articulate and evidence of subtle weakness and
  loss of reflexes may be overlooked.
• There is a lack of adequate randomized controlled
  treatment trials in children to define the role
  of either PE or IVIg.

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Conclusion

• There are no adequate randomized controlled
  trials of treatment in children.
•  

Recommendation

• Plasma exchange or IVIg are treatment options for
  treating children with severe GBS (Level B
  recommendation derived from class II evidence in
  adults).

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Future research

• More research is needed to evaluate immunotherapy
  in GBS, particularly the use of combination
  treatments and further treatment after the
  initial course.
• There is a need to identify patients who are at
  greater risk of an adverse outcome and to
  discover whether subgroups have differential
  responses to treatment (including children,
  people with axonal forms of GBS, and Fishers
  syndrome).
• Research should also investigate the best methods
  of supportive care for monitoring autonomic and
  pulmonary function, weaning from ventilation,
  treating pain, managing fatigue, and
  rehabilitation.

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Summary of AAN recommendations for immunotherapy
for GBS

• 1. Plasma exchange is recommended in
• non-ambulant adult patients with GBS who
  present within four weeks from the onset of
  neuropathic symptoms. Plasma exchange should
  also be considered in ambulant patients who
  present within two weeks from the onset of
  neuropathic symptoms.

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Summary of AAN recommendations for immunotherapy
for GBS

• 2. Intravenous immunoglobulin (IVIg) is
  recommended in non-ambulant adult patients with
  GBS within two or possibly four weeks from the
  onset of neuropathic symptoms. The effects of
  plasma exchange and IVIg are equivalent.
• 3. Corticosteroids are not recommended in the
  treatment of GBS.

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Summary of AAN recommendations for immunotherapy
for GBS

• 4. Sequential treatment with PE followed by IVIg
  or immunoabsorption followed by IVIg is not
  recommended for GBS.
• 5. Plasma exchange or IVIg are treatment options
  for treating children with severe GBS.