gbs immunoterapi
TRANSCRIPT
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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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ðods 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( $$7 ) $da*s; Control group &n'"( $5") +$ da*s
/he mean reco0ery time in days3as almost identical bet3een thet3o !roups
PE 7++ ) !!4 ,s
-upporti,e .reatent 7#$ )55!
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Analysis of the e0idence
Author/Year
Class
Results
*rench#o-opGroup on
plasmae?chan!e inGBS%56JH(o!are )*+ith su!!orti"e
treatent
II"#/
P patients reco0ered 3alin! 3ithassistance faster than the controlpatients (pK25)
"eco0ered 5 or more disability!rades after 3ees
PE group +7/$0#;Control group 4$/$$$
*or 0entilated patients% time toonset of reco0er 3alin! assistance3as shorter in the P than thecontrol !roup (pK2E)
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Analysis of the e0idence
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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Analysis of the e0idence
#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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Analysis of e0idence
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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Analysis of the e0idence
Immunoabsorption
An alternati0e techni;ue to P% 3hichremo0es immuno!lobulins2
$as the ad0anta!e of not re;uirin! the use ofa human blood product as a replacementfluid2
In a prospecti0e trial there 3ere nodifferences in outcome bet3een 55 patientstreated 3ith P and 5C treated 3ithimmunoabsorption
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/here is only limited #lass I= e0idence froma sin!le small non-randomirecommendation% #lass I= e0idence)2
Recoendation
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Analysis of the e0idence
Steroids #ochrane systematic re0ie3 sou!ht all trials
of any form of corticosteroid oradrenocorticotrophic hormone treatment for
GBS2 Si? randomi
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Analysis of e0idence
Author/Year Class Results
S3ic and&cQuillen%56H7
*ect o (
II
"#/
A0era!e disease duration%e?cludin! one A#/$ patient3ho died
AC.3 group 44 onths;Placeo patients #0onths
$u!hes etal2% 56HJ
*ect o!re/nisolone
II
"#/
4ess impro0ement in disability!rade after one% three and 5D
months in the prednisolonethan the untreated patients%3hich 3as si!nificant (pK2E)for those randomi
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Analysis of e0idence
Author/Year
Class Results
&endell etal2% 56JE*ect o
!lasaechange an/
!re/nisone
IIAlternateallocationcontrolledtrial
o si!nificant difference inany outcome
Shula etal2% 56JJ*ect o
!re/nisolone
I "#/ o si!nificant difference inany outcome
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Analysis of e0idenceAuthor/Year
Class Results
GBS Steroid/rial Group%566C*ect o i"ethyl-
!re/nisolone
I "#/ /he mean difference indisability !rade after four3ees 3as 27 (-2DC N
2C7) !rade moreimpro0ement in thesteroid than the placebo!roup
either this nor any otheroutcome 0ariable sho3eda si!nificant difference
Sin!h et al2%5667*ect o
!re/nisolone
IIAlternateallocation
#/
o si!nificant difference inany outcome
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Analysis of e0idence
Author/Year
Class Results
/he 'utchGBS Group%
566*ect o i"ethyl-)re/nisolonea//e/ to ,,g
IIIobser0ationa
l series 3ithhistoricalcontrols
7+% ipro,ed one grade;
Control group 5"%
&p'004(
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Question #2:
re there s!ecial issues in theanageent o chil/ren +ith$%&'
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Analysis of the e0idence
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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Summary of AArecommendations for
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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Summary of AArecommendations for
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