GBS immunoterapi

8/13/2019 GBS immunoterapi

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1b,ecti0e of the !uideline:

/o pro0ide an e0idence-based statement to!uide physicians in the mana!ement ofGuillain-Barr syndrome (GBS)2


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&ethods of e0idence re0ie3: &'4I search from 5677 and the #ochrane

library (March 2002)2

8Polyradiculoneuritis9 limited by 8human9 andcross referenced 3ith 8therapy29

Search results 3ere re0ie3ed by at least t3omembers of the GBS practice parameter

!roup2 "ecommendations 3ere !raded accordin! to

the le0els established by the AAs QualityStandards Subcommittee (QSS)2


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AAs#lass of e0idence for therapy

#lass I2 $i!h ;uality randomi


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AAs

"ecommendation 4e0els4e0elA

stablished as effecti0e% ineffecti0e orharmful% or as useful@predicti0e or notuseful@predicti0e

4e0elB

Probably effecti0e% ineffecti0e or harmful%or as useful@predicti0e or notuseful@predicti0e

4e0el#

Possibly effecti0e% ineffecti0e or harmful%or as useful@predicti0e or notuseful@predicti0e

4e0el>

'ata inade;uate or conflictin! /reatment%test% or predictor unpro0en


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Introduction:

Pre0alence:

GBS affects bet3een one and four per 5% of

the 3orlds population annually2

conomic Impact:

/he costs in the >S ha0e been estimated as

55% for direct health care and C7% inlost producti0ity per patient2


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Introduction:

$ealth 1utcomes:

"espiratory failure re;uirin! 0entilation in

about DEF of patients 3ith GBS 'eath in F to 5EF of GBS patients

Persistent disability in about DF patients 3ithGBS

Persistent fati!ue in 7HF of patients 3ithGBS


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Question #1:

Does initial iunothera!yhasten reco"ery ro $%&sy!tos'


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'ia!nostic criteriaIn most studies% the primary outcome measureused disability scale% 3here: normal 5 symptoms but able to run D unable to run C unable to 3al unaided bed-bound E needin! 0entilation 7 dead

&ost studies included patients 3ith se0eredisease%

at least !rade C on that scale2


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Analysis of the e0idence

Plasma ?chan!e

#ochrane re0ie3 obtained data from si? #lassII trials comparin! plasma e?chan!e (P) alone

to supporti0e care /he P re!imens in0ol0ed e?chan!in! about

one plasma 0olume on fi0e separate occasionsspaced out o0er one to t3o 3ees

1ne trial 3hich used t3o plasma 0olumee?chan!es on alternate days for a total of foure?chan!es


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Analysis of the e0idenceAuthor/Ye

ar

Clas

s

Results

/heGuillain-Barrsyndrome

StudyGroup%56JE(o!are )*+ith su!!orti"etreatent

II"#/

Impro0ement by one or more!rades at one month (pK25)

PE group 5#%;Control group "#%

*ailed to reco0er 3alin!unaided after 7 months2(pK2E)

PE group $!%;

Control group #%

=entilated patients impro0ementby one or more disability !radesat one month (pK25)

PE group 50%;Control group "5%


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Analysis of the e0idenceAuthor

/ Year

Class Results

*arila% 56JH(o!are)* +ith

su!!orti"etreatent

II "#/ $and!rip stren!th 3assi!nificantly !reater in the P!roup (pK25)

/he mean (L S') time on0entilator 3as sli!htly shortened

PE group &n'4( $$7 ) $da*s; Control group &n'"( $5") +$ da*s

/he mean reco0ery time in days3as almost identical bet3een thet3o !roups

PE 7++ ) !!4 ,s

-upporti,e .reatent 7#$ )55!


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Author/Year

Class

Results

*rench#o-opGroup on

plasmae?chan!e inGBS%56JH(o!are )*+ith su!!orti"e

treatent

II"#/

P patients reco0ered 3alin! 3ithassistance faster than the controlpatients (pK25)

"eco0ered 5 or more disability!rades after 3ees

PE group +7/$0#;Control group 4$/$$$

*or 0entilated patients% time toonset of reco0er 3alin! assistance3as shorter in the P than thecontrol !roup (pK2E)


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Author /Year

Class Results

*rench

#o-op

Group onplasmae?chan!e inGBS%

566H(o!are )* +ithsu!!orti"etreatent

II "#/ In the P !roup% time to onset ofmotor reco0ery 3as si!nificantly

shortened compared to thecontrol !roup (p2D)2

/he number of patients 3ith oneor more !rades of impro0ement

at one month 3as si!nificantlymore

PE group 5+5%;

Control group !"%


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#onclusions Plasma e?chan!e hastens reco0ery in non-

ambulant patients 3ith GBS 3ho present 3ithinfour 3ees from the onset of neuropathicsymptoms (#lass II e0idence)2

Plasma e?chan!e also hastens reco0ery inambulant patients 3ho present 3ithin t3o 3ees

but the e0idence is limited to one trial (#lass IIe0idence)2

/he effects of plasma e?chan!e and I=I! aree;ui0alent in patients re;uirin! aid to 3al(#lass I

e0idence)2

/reatment 3ith #S* filtration has not beenade;uately tested (4imited #lass II e0idence)2


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"ecommendations

P is recommended in non-ambulant patients3ithin four 3ees from onset (4e0el A% #lass II

e0idence)2

P is recommended for ambulant patients3ithin t3o 3ees from onset (4e0el B% limited#lass II e0idence)2


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Analysis of the e0idenceI= Immuno!lobulin /hree trials compared I=I! 3ith P2 /he mean

impro0ement in disability !rade four 3eesafter randomi


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Analysis of the e0idenceAuthor/Year

Class Results

0an der&ech%

et al2% 566D(o!are ,,g+ith )*

II on-blinded

"#/

Patients impro0ed by one ormore !rades (p2D) after

four 3eesIIg group 5"%;PE group "4%

&edian time to reco0ery of

unaided 3alin! (p2H)IIg group 55 da*s;PE group +#da*s


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Analysis of the e0idenceAuthor/Ye

ar

Class Results

GMrses%566E(o!are ,,$+ith su!!orti"etreatent

IIIAlternateallocation#ontrolledtrial(children)

"eco0ered full stren!thafter four 3ees (p27)

IIg group 77!%;Control group %

&edian time to reco0erunaided 3alin!

IIg group $5 da*s&r'$$10(;

Control group 45da*s &r'$1!(

After one year all the I=I!patients had reco0ered


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Conclusions

Intra0enous immuno!lobulin has not beenade;uately compared 3ith placebo (limited#lass II e0idence)2

Such comparison is not no3 needed because%3hen started 3ithin t3o 3ees from the

onset% I=I! has e;ui0alent efficacy to P inhastenin! reco0ery from patients 3ith GBS3ho re;uire aid to 3al (#lass I e0idence)2

&ultiple complications 3ere si!nificantly lessfre;uent 3ith I=I! than 3ith P (#lass Ie0idence)2

/here is no e0idence concernin! the relati0eefficacy of P and I=I! in patients 3ith a?onalforms of GBS2


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Recoendations

I=I! is recommended for patients 3ith GBS3ho re;uire aid to 3al 3ithin t3o (4e0el Arecommendation) or four 3ees from theonset of neuropathic symptoms (4e0el Brecommendation deri0ed from #lass II

e0idence concernin! P started 3ithin thefirst four 3ees)2

/he effects of I=I! and plasma e?chan!e are

e;ui0alent2 (4e0el B recommendation #lass Ie0idence concernin! the comparisonsbet3een P and I=I! started 3ithin the firstt3o 3ees)2


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#ombination treatments

1ne #lass I trial sho3ed that P follo3ed byI=I! sho3ed no si!nificant benefit compared3ith P alone in any measured outcome2


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Analysis of e0idence

Author/Year

Class

Results

PSGBSGroup%

566Ho co!are ,,g+ith )* an/ +ith)* ollo+e/ y,,g

IISin!l

eblind

"#/

o si!nificant differencein any outcome measure

bet3een any of the threere!imens

/he difference bet3eenthe chan!e in disability!rade bet3een P andI=I! 3as so small as tofulfill pre0iously declaredcriteria for e;ui0alence


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Author/ Year

Class

Results

omura

et al2%D5o co!are,,g +ith )*an/ +ith )*ollo+e/ y

,,g

II

"#/

o si!nificant difference in

any outcome measure


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Conclusions

Se;uential treatment 3ith P follo3ed by I=I!does not ha0e a superior effect to eithertreatment !i0en alone (#lass I e0idence)2

Se;uential treatment 3ith immunoabsorptionfollo3ed by I=I! has not been ade;uately

tested (4imited #lass I= e0idence)2


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Recoendations

Se;uential treatment 3ith P follo3ed by I=I!is not recommended (4e0el Arecommendation% #lass I e0idence)2

Immunoabsorption follo3ed by I=I! is notrecommended (4e0el > recommendation%#lass I= e0idence)2


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Immunoabsorption

An alternati0e techni;ue to P% 3hichremo0es immuno!lobulins2

$as the ad0anta!e of not re;uirin! the use ofa human blood product as a replacementfluid2

In a prospecti0e trial there 3ere nodifferences in outcome bet3een 55 patientstreated 3ith P and 5C treated 3ithimmunoabsorption


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/here is only limited #lass I= e0idence froma sin!le small non-randomirecommendation% #lass I= e0idence)2

Recoendation


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Steroids #ochrane systematic re0ie3 sou!ht all trials

of any form of corticosteroid oradrenocorticotrophic hormone treatment for

GBS2 Si? randomi


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Author/Year Class Results

S3ic and&cQuillen%56H7

*ect o (

II

"#/

A0era!e disease duration%e?cludin! one A#/$ patient3ho died

AC.3 group 44 onths;Placeo patients #0onths

$u!hes etal2% 56HJ

*ect o!re/nisolone

II

"#/

4ess impro0ement in disability!rade after one% three and 5D

months in the prednisolonethan the untreated patients%3hich 3as si!nificant (pK2E)for those randomi


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Author/Year

Class Results

&endell etal2% 56JE*ect o

!lasaechange an/

!re/nisone

IIAlternateallocationcontrolledtrial

o si!nificant difference inany outcome

Shula etal2% 56JJ*ect o

!re/nisolone

I "#/ o si!nificant difference inany outcome


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Analysis of e0idenceAuthor/Year

Class Results

GBS Steroid/rial Group%566C*ect o i"ethyl-

!re/nisolone

I "#/ /he mean difference indisability !rade after four3ees 3as 27 (-2DC N

2C7) !rade moreimpro0ement in thesteroid than the placebo!roup

either this nor any otheroutcome 0ariable sho3eda si!nificant difference

Sin!h et al2%5667*ect o

!re/nisolone

IIAlternateallocation

#/

o si!nificant difference inany outcome


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Author/Year

Class Results

/he 'utchGBS Group%

566*ect o i"ethyl-)re/nisolonea//e/ to ,,g

IIIobser0ationa

l series 3ithhistoricalcontrols

7+% ipro,ed one grade;

Control group 5"%

&p'004(


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Question #2:

re there s!ecial issues in theanageent o chil/ren +ith$%&'


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GBS in #hildren /he clinical features of GBS in children are

similar to those in adults e?cept that se0ereconditions are less common and a?onal forms of

the disease are more fre;uent in somepopulations2

In youn!er children% in particular% pain isfre;uently the only symptom they are able toarticulate and e0idence of subtle 3eaness andloss of refle?es may be o0erlooed2

/here is a lac of ade;uate randomi


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/here are no ade;uate randomi


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*uture research &ore research is needed to e0aluate

immunotherapy in GBS% particularly the use ofcombination treatments and further treatmentafter the initial course2

/here is a need to identify patients 3ho are at!reater ris of an ad0erse outcome and to

disco0er 3hether sub!roups ha0e differentialresponses to treatment (includin! children%people 3ith a?onal forms of GBS% and *isherssyndrome)2

"esearch should also in0esti!ate the best

methods of supporti0e care for monitorin!autonomic and pulmonary function% 3eanin!from 0entilation% treatin! pain% mana!in!fati!ue% and rehabilitation2


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Summary of AArecommendations for

immunotherapy for GBS

52 Plasma e?chan!e is recommended innon-ambulant adult patients 3ith GBS

3ho present 3ithin four 3ees from theonset of neuropathic symptoms2

Plasma e?chan!e should also beconsidered in ambulant patients 3ho

present 3ithin t3o 3ees from theonset of neuropathic symptoms2


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immunotherapy for GBSD2 Intra0enous immuno!lobulin (I=I!) is

recommended in non-ambulant adult

patients 3ith GBS 3ithin t3o or possiblyfour 3ees from the onset ofneuropathic symptoms2 /he effects ofplasma e?chan!e and I=I! aree;ui0alent2

C2 #orticosteroids are not recommendedin the treatment of GBS2


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immunotherapy for GBS

2 Se;uential treatment 3ith P follo3ed by I=I!or immunoabsorption follo3ed by I=I! is notrecommended for GBS2

E2 Plasma e?chan!e or I=I! are treatmentoptions for treatin! children 3ith se0ere GBS2

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