GBS_Edu_tool_V3

7/29/2019 GBS_Edu_tool_V3

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Practice Parameter: Immunotherapyfor Guillain-Barr 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 2003;61:736-740.


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Objective of the guideline:

To provide an evidence-based statement to guidephysicians in the management of Guillain-Barrsyndrome (GBS).


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Methods of evidence review:

MEDLINE search from 1966 and the Cochrane library(March 2002).

Polyradiculoneuritis limited by human and crossreferenced with therapy.

Search results were reviewed by at least twomembers of the GBS practice parameter group.

Recommendations were graded according to thelevels established by the AANs Quality Standards

Subcommittee (QSS).


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AANs

Class of evidence for therapy

Class I. High quality randomized controlled trials(RCTs)

Class II. Prospective matched group cohort studies or

RCTs lacking adequate randomizationconcealment or blinding, or potentially liable toattrition or outcome ascertainment bias

Class

III.

Other studies such as natural history studies

ClassIV.

Uncontrolled studies, case series, or expertopinion


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AANs

Recommendation LevelsLevel

AEstablished as effective, ineffective or harmful,or as useful/predictive or not useful/predictive

LevelB

Probably effective, ineffective or harmful, or asuseful/predictive or not useful/predictive

LevelC

Possibly effective, ineffective or harmful, or asuseful/predictive or not useful/predictive

LevelU

Data inadequate or conflicting; Treatment, test,or predictor unproven


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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 productivityper 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 hastenrecovery from GBS symptoms?


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Diagnostic criteriaIn most studies, the primary outcome measureused 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 trialscomparing plasma exchange (PE) alone to

supportive care

The PE regimens involved exchanging about oneplasma volume on five separate occasions spacedout over one to two weeks

One trial which used two plasma volume exchangeson alternate days for a total of four exchanges


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Analysis of the evidenceAuthor / Year Class Results

Greenwood,1984Compare PE with

supportive treatment

IIRCT

Improved by one or more disabilitygrades after four weeks

PE group 50%;

Control group 40%

Osterman,1984Compare PE with


IIRCT

Improved by one or more disabilitygrades after four weeks (p


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Analysis of the evidenceAuthor/Year Class Results

The Guillain-BarrsyndromeStudy Group,

1985Compare PE withsupportive

treatment

IIRCT

Improvement by one or more gradesat one month (p


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Analysis of the evidenceAuthor /

Year

Class Results

Farkkila,1987Compare

PE with

supportivetreatment

II RCT Handgrip strength was significantlygreater in the PE group (p


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Author/Year Class Results

FrenchCo-op Groupon plasma

exchange inGBS,1987Compare PE with

supportive

treatment

IIRCT

PE patients recovered walking withassistance faster than the controlpatients (p


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Author /Year

Class Results

French

Co-op Group

on plasmaexchange inGBS,

1997Compare PE with


II RCT In the PE group, time to onset ofmotor recovery was significantly

shortened compared to the controlgroup (p=0.0002).

The number of patients with one ormore grades of improvement at onemonth was significantly more

PE group 56.5%;

Control group 28.3%


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Conclusions Plasma exchange hastens recovery in non-ambulant

patients with GBS who present within four weeks from theonset of neuropathic symptoms (Class II evidence).

Plasma exchange also hastens recovery in ambulantpatients who present within two weeks but the evidence islimited to one trial (Class II evidence).

The effects of plasma exchange and IVIg are equivalent inpatients 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 patientswithin four weeks from onset (Level A, Class II

evidence).

PE is recommended for ambulant patients within twoweeks from onset (Level B, limited Class IIevidence).


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Analysis of the evidenceIV Immunoglobulin

Three trials compared IVIg with PE. The meanimprovement in disability grade four weeks afterrandomization was available.

In one Class III trial comparing IVIg with supportivetreatment, seven of nine children who received IVIgrecovered completely by four weeks compared withtwo of nine untreated.

Cochrane systematic review found no trialscomparing IV immunoglobulin (IVIg) with placebo.


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van derMech,

et al., 1992Compare IVIg withPE

II Non-blinded

RCT

Patients improved by one ormore grades (p=0.024) after

four weeksIVIg group 53%;PE group 34%

Median time to recovery of

unaided walking (p=0.07)IVIg group 55 days;

PE group 69days


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Analysis of the evidenceAuthor/Year Class Results

Grses,1995Compare IVIG

with supportive

treatment

III AlternateallocationControlledtrial

(children)

Recovered full strength afterfour weeks (p=0.06)

IVIg group 77.8%;

Control group 22.2%

Median time to recoverunaided walking

IVIg group 15 days (r=11-

20);

Control group 24.5 days

(r=21-28)

After one year all the IVIgpatients had recovered


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Bril, et al., 1996

Compare IVIG withsupportive treatment

II RCT Median time to recover ability

to do manual workIVIg group 65 days;

PE group 90 days

Mean disability gradeimprovement

IVIg group 1.2;

PE group 1.0


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Conclusions

Intravenous immunoglobulin has not beenadequately compared with placebo (limited Class IIevidence).

Such comparison is not now needed because, whenstarted within two weeks from the onset, IVIg has

equivalent efficacy to PE in hastening recovery frompatients with GBS who require aid to walk (Class Ievidence).

Multiple complications were significantly lessfrequent with IVIg than with PE (Class I evidence).

There is no evidence concerning the relative efficacyof PE and IVIg in patients with axonal forms of GBS.


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Recommendations

IVIg is recommended for patients with GBS whorequire aid to walk within two (Level Arecommendation) or four weeks from the onset ofneuropathic symptoms (Level B recommendationderived from Class II evidence concerning PE

started within the first four weeks).

The effects of IVIg and plasma exchange areequivalent. (Level B recommendation Class I

evidence concerning the comparisons between PEand IVIg started within the first two weeks).


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Combination treatments

One Class I trial showed that PE followed by IVIgshowed no significant benefit compared with PEalone in any measured outcome.


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Analysis of evidence

Author/Year Class ResultsPSGBSGroup, 1997To compare IVIg

with PE and with

PE followed by IVIg

IISingleblind

RCT

No significant difference inany outcome measurebetween any of the three

regimens The difference between the

change in disability gradebetween PE and IVIg was so

small as to fulfill previouslydeclared criteria forequivalence


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Author /

YearClass Results

Nomura

et al.,2001To compareIVIg with PEand with PEfollowed by

IVIg

II RCT No significant difference in any

outcome measure


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Conclusions

Sequential treatment with PE followed by IVIg doesnot have a superior effect to either treatment givenalone (Class I evidence).

Sequential treatment with immunoabsorptionfollowed by IVIg has not been adequately tested

(Limited Class IV evidence).


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Recommendations

Sequential treatment with PE followed by IVIg is notrecommended (Level A recommendation, Class Ievidence).

Immunoabsorption followed by IVIg is notrecommended (Level U recommendation, Class IVevidence).


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Immunoabsorption

An alternative technique to PE, which removesimmunoglobulins.

Has the advantage of not requiring the use of ahuman blood product as a replacement fluid.

In a prospective trial there were no differences inoutcome between 11 patients treated with PE and13 treated with immunoabsorption


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

Conclusion

The evidence is insufficient to recommend the use ofimmunoabsorption (Level U recommendation, ClassIV evidence).

Recommendation


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Steroids

Cochrane systematic review sought all trials of anyform of corticosteroid or adrenocorticotrophichormone treatment for GBS. Six randomized trials

were identified. The corticosteroid regimens included intramuscular

ACTH, intravenous methylprednisolone,oralprednisolone, or prednisone.

The primary outcome measure in the systematicreview was the improvement in disability grade fourweeks after randomization.


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Author/Year Class ResultsSwick andMcQuillen,1976Effect of ACTH

II

RCT

Average disease duration, excludingone ACTH patient who died

ACTH group 4.4 months;

Placebo patients 9.0 months.

Hughes et al.,1978Effect of

prednisolone

II

RCT

Less improvement in disability gradeafter one, three and 12 months inthe prednisolone than the untreatedpatients, which was significant

(p


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Mendell etal., 1985Effect of plasma

exchange and

prednisone

II Alternateallocationcontrolledtrial

No significant difference in anyoutcome

Shukla et al.,1988Effect of

prednisolone

I RCT No significant difference in anyoutcome


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Analysis of evidenceAuthor/Year Class Results

GBS SteroidTrial Group,1993Effect of iv

methyl-

prednisolone

I RCT The mean difference indisability grade after fourweeks was 0.06 (-0.23 0.36)grade more improvement in

the steroid than the placebogroup

Neither this nor any otheroutcome variable showed asignificant difference

Singh et al.,1996Effect of

prednisolone

II AlternateallocationCT

No significant difference in anyoutcome


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The DutchGBS Group,1994

Effect of ivmethyl-

Prednisolone

added to IVIg

IIIobservationalseries with

historicalcontrols

76% improved one grade;

Control group 53% (p=0.04)


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The combined evidence from all trials shows nobenefit from corticosteroids (Class I evidence).

The results of a trial of the combination ofintravenous methylprednisolone and IVIg are

awaited.

Conclusion

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

Recommendation


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Question #2:

Are there special issues in the

management of children with GBS?


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GBS in Children

The clinical features of GBS in children are similar tothose in adults except that severe conditions are lesscommon 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 evidenceof subtle weakness and loss of reflexes may beoverlooked.

There is a lack of adequate randomized controlledtreatment trials in children to define the role of eitherPE or IVIg.


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There are no adequate randomized controlledtrials of treatment in children.

Conclusion

Plasma exchange or IVIg are treatment options fortreating children with severe GBS (Level B

recommendation derived from class II evidence inadults).

Recommendation


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Future research More research is needed to evaluate immunotherapy

in GBS, particularly the use of combinationtreatments and further treatment after the initialcourse.

There is a need to identify patients who are at greaterrisk 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 ofsupportive care for monitoring autonomic and

pulmonary function, weaning from ventilation, treatingpain, managing fatigue, and rehabilitation.


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Summary of AANrecommendations for

immunotherapy for GBS

1. Plasma exchange is recommended innon-ambulant adult patients with GBS

who present within four weeks from theonset of neuropathic symptoms. Plasmaexchange should also be considered inambulant patients who present within

two weeks from the onset of neuropathicsymptoms.


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immunotherapy for GBS2. Intravenous immunoglobulin (IVIg) is

recommended in non-ambulant adult patients

with GBS within two or possibly four weeksfrom the onset of neuropathic symptoms. Theeffects of plasma exchange and IVIg areequivalent.

3. Corticosteroids are not recommended in thetreatment of GBS.


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immunotherapy for GBS

4. Sequential treatment with PE followed by IVIg orimmunoabsorption followed by IVIg is not

recommended for GBS.

5. Plasma exchange or IVIg are treatment options fortreating children with severe GBS.

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