Articles

Lancet 2005; 366:

136C43 See Comment
page 100
Institute of Social
Medicine !"idemiolo#$
and %ealt&
!conomics(C Witt
MD, BBrinkhaus MD, S
Jena MSc,
ProfS N Willich MD) and
Centre for Musculos'eletal
Sur#er$
(! Walther MD),
C&arit( )ni*ersit$
Medical Centre
+erlin ,erman$; Centre
for Com"lementar$
Medicine
-esearc& .e"artment
of Internal Medicine II ("
#in$e MD,
% Streng PhD, D Melchart
MD) and Institute of
Medical
Statistics and
!"idemiolo#$ (SWagenpfeil
PhD), /ec&nisc&e
)ni*ersit0t M1nc&en
Munic&
,erman$; .i*ision
of Com"lementar$
Medicine
.e"artment of
Internal Medicine
)ni*ersit$ %os"ital
2uric& 2uric&
S3it4erland (DMelchart
MD)& and
International Societ$ for C&inese Medicine SocietasAcu"uncture in "atients 3it&
osteoart&ritis of t&e 'nee: arandomised trial
C Witt, B Brinkhaus, S Jena," #in$e, % Streng, S Wagenpfeil, J u''els(erger, ! Walther, D Melchart,S N
Willich
Summar$
+ac'#round Acu"uncture is 3idel$ used 5$ "atients 3it& c&ronic "ain alt&ou#& t&ere is little e*idence of
its effecti*eness6 7e in*esti#ated t&e ef8cac$ of acu"uncture com"ared 3it& minimal acu"uncture and
3it& no acu"uncture in "atients 3it& osteoart&ritis of t&e 'nee6
Met&ods 9atients 3it& c&ronic osteoart&ritis of t&e 'nee :;ell#ren #rade 2< 3ere randoml$ assi#ned to
acu"uncture :n=150< minimal acu"uncture :su"er8cial needlin# at non>acu"uncture "oints; n=?6< or a
3aitin# list control :n=?4<6 S"ecialised "&$sicians in 2@ out"atient centres administered acu"uncture and
minimal acu"uncture in 12 sessions o*er @ 3ee's6 9atients com"leted standard Auestionnaires at
5aseline and after @ 3ee's 26 3ee's and 52 3ee's6 /&e "rimar$ outcome 3as t&e 7estern Bntario and
McMaster )ni*ersities Bsteoart&ritis :7BMAC< indeC at t&e end of 3ee' @ :adDusted for 5aseline score<6 All
main anal$ses 3ere 5$ intention to treat6
-esults 2E4 "atients 3ere enrolled from Marc& 6 2002 to Fanuar$ 1? 2003; ei#&t "atients 3ere lost to
follo3>u" after randomisation 5ut 3ere included in t&e 8nal anal$sis6 /&e mean 5aseline>adDusted
7BMAC indeC at 3ee' @ 3as 26GHE :S! 1GH4< in t&e acu"uncture #rou" 35GH@ :1GHE< in t&e minimal
acu"uncture #rou" and 4EGH6 :2GH0< in t&e 3aitin# list #rou" :treatment difference acu"uncture vs minimal
acu"uncture C@GH@ IE5J CI C13GH5 to C4GH2K "=0GH0002; acu"uncture vs 3aitin# list C22GH? IC2?GH5 to
C1?GHEK "0GH0001<6 After 52 3ee's t&e difference 5et3een t&e acu"uncture and minimal acu"uncture
#rou"s 3as no lon#er si#ni8cant :"=0GH0@<6
Inter"retation After @ 3ee's of treatment "ain and Doint function are im"ro*ed more 3it& acu"uncture
t&an 3it& minimal acu"uncture or no acu"uncture in "atients 3it& osteoart&ritis of t&e 'nee6 %o3e*er
t&is 5ene8t decreases o*er time
6Medicinae Sinensis
Munic& ,erman$ (J
u''els(erger MD)
Correspon$ence
to) Dr Clau$ia Witt,
*nstitute of
Social Me$icine,
+pi$e'iolog,, an$ ealth
+cono'ics, Charit-.
!ni/ersit, Me$ical
Centre, 10001Berlin,
2er'an,
claudia63ittLc&arite6deIntroduction
3steoarthritis 'ost fre4uentl, affects the knee 5oint61
%nti7in8a''ator, $rugs use$ to treat the s,'pto's of
this $isor$er are associate$ 9ith /arious si$e7effects6:
; <urther'ore, for patients for 9ho' these $rugs $o not
lea$ to an a$e4uate response, replace'ent surger, is
often reco''en$e$6Patients 9ith chronic pain are
increasingl, using acupuncture for pain relief6=>?here is
so'e e/i$ence that acupuncture can (e effecti/e in
treating pain an$ $,sfunction in patients 9ith
osteoarthritis of the knee6 *n a s,ste'atic re/ie9
inclu$ing se/en ran$o'ise$ controlle$ trials 9ith a total
of ;0; patients, acupuncture 9as 'ore effecti/e than
sha' acupuncture in re$ucing pain, 9hereas for 5oint
function the results 9ere inconclusi/e6?hese pre/ious
stu$ies, ho9e/er, 9ere (ase$ on s'all sa'ple si@es an$
the follo97up perio$ 9as ne/er longer than ; 'onths6
We ai'e$ to in/estigate the efAcac, of acupuncture
co'pare$ 9ith 'ini'al acupuncture an$ 9ith no
acupuncture in patients 9ith pain an$ $,sfunction $ue to
osteoarthritis of the knee6
Met&ods
9atients
Patients 9ere
inclu$e$ in our stu$,
if the, 9ere age$
=0-CB= ,ears, ha$
(een $iagnose$ 9ith
osteoarthritis
accor$ing to the
%'erican College of
Cheu'atolog,
criteria, ha$
$ocu'ente$
ra$iological
alterations in
theD,Bknee 5oint of
gra$e : or 'ore
accor$ing to "ellgren#a9rence criteria,ha$ an
a/erage pain intensit, of >0 or 'ore on a 100 ''
/isual analogue scale in the B $a,s (efore (aseline
assess'ent, an$ if the, ga/e 9ritten infor'e$
consent6 ?he eEclusion criteria 9ere one or 'ore of
the follo9ing) pain in the knee cause$ (, in8a''ator,,
'alignant, or autoi''une $isease& or other reasons
for pain in the knee, such as serious /algus7$efecti/e
or /arus7$efecti/e position6 Patients 9ere also
eEclu$e$ if the, ha$ ha$ knee surger,, arthroscop, of
the affecte$ knee in the past ,ear, chon$roprotecti/e
or intra7articular in5ection in the past > 'onths,
s,ste'ic corticoi$ treat'ent or (eginning of a ne9
treat'ent for osteoarthritis in the past > 9eeks, local
antiphlogistic treat'ent, acupuncture treat'ent $uring
the past 1: 'onths, or ph,siotherap, or other
treat'ents for osteoarthritis knee pain (9ith the
eEception of nonsteroi$al anti7in8a''ator, $rugs)
$uring the pre/ious >9eeks6 %$$itional eEclusion
criteria 9ere application for pension or $isa(ilit,
(eneAts, serious acute or chronic organic $isease or
'ental $isor$er, pregnanc, or (reastfee$ing, an$
(loo$ coagulation $isor$ers or coagulation7inhi(iting
'e$ication other than aspirin6 Most participants 9ere
recruite$ through reports in local ne9spapers& a fe9
patients spontaneousl, contacte$ trial centres6 %ll
stu$, participants pro/i$e$ 9ritten infor'e$ consent
an$ 9ere insure$ accor$ing to the 2er'an la9 for
'e$ical pro$ucts
6136 9996thelancet6co' Mol 366 Ful$ E 2005
9rocedures
1<igure 1 sho9s the stu$, $esign6 Patients
9ere ran$o'l, assigne$ to a treat'ent group
stratiAe$ (, centre in a :) 1) 1 ratio
(acupuncture) 'ini'al acupuncture) 9aiting
list) 9ith a centralise$ telephone
ran$o'isation proce$ure (ran$o' list
generate$ 9ith Sa'p Si@e :FG0)6 ?he :) 1) 1
ratio 9as use$ to help 9ith recruit'ent an$
increase the co'pliance of trial ph,sicians6
Mini'al acupuncture ser/e$ as a sha'
inter/ention& the a$$itional no acupuncture
9aiting list control 9as inclu$e$ since 'ini'al
acupuncture 'ight not (e a ph,siologicall,
inert place(o6 Patients in the acupuncture an$
'ini'al acupuncture groups 9ere una9are of
their treat'ent allocation6 ?he total follo9up
stu$, perio$ per patient 9as =: 9eeks6 ?he
stu$, 9as un$ertaken accor$ing to co''on
gui$elines for clinical trials (Declaration of
elsinki, *C72CP inclu$ing certiAcation (,
an eEternal au$it)6 ?he stu$, protocol 9as
appro/e$ (, the appropriate ethics re/ie9
(oar$s an$ has (een $escri(e$ in $etail
else9here6
Stu
$,
inte
r/e
ntio
ns
9er
e
$e/
elo
pe$
in a
con
sen
sus
pro
ces
s
9ith
acu
pun
ctur
e
eEp
erts
an$
soci
etie
s,
an$
pro
/i$
e$
(,
ph,
sici
ans
9h
o
9er
e
trai
ne$
(at
lea
st
1>0
h)
an$
eEp
erie
nce
$ in
acupuncture6
Both the
acupuncture an$
'ini'al
acupuncture
treat'ents
consiste$ of 1:
sessions of ;0
'in $uration,
a$'inistere$ o/er
1 9eeks (usuall,
t9o sessions per
9eek for the
> 9eeks, follo9e$
(, one session
per 9eek in the
re'aining >
9eeks)6 <or
patients 9ith
(ilateral
osteoarthritis in
the acupuncture
an$ the 'ini'al
acupuncture
groups, (oth
knees 9ere
nee$le$ 9ith at
least eight out of
ten propose$
points (at least 1D
nee$les
altogether),
9hereas for
patients 9ith
unilateral
osteoarthritis, the
ph,sician 9as
a(le to choose
unilateral or
(ilateral
acupuncture6 <or
unilateral
acupuncture, the
treat'ent ha$ to
(e $one 9ith at
least eight
nee$les6 Patients
in the 9aiting list
group $i$ not
recei/e
acupuncture
treat'ent for a
perio$ of 1
9eeks, after
9hich ti'e the,
then also
recei/e$
acupuncture6
icl
es
1Mini'al acupuncture treat'ent entaile$
superAcial insertion of Ane nee$les
(:0-C>0 '' in length) at pre$eAne$,
$istant non7acupuncture points6?hese
nonacupuncture points 9ere not in the
area of the knee, an$ the selection of at
least eight out of ten points 9as left to the
ph,sicianFHs $iscretion6 Ph,sicians 9ere
instructe$ to a/oi$ 'anual sti'ulation of
the nee$les an$ pro/ocation of $e 4i in the
'ini'al acupuncture treat'ent6 *n
in/estigator 'eetings, all acupuncturists
recei/e$ training in the application of
'ini'al acupuncture, 9hich inclu$e$ a
/i$eotape an$ a (rochure sho9ing $etaile$
infor'ation a(out the proce$ure6
Patients in the 9aiting list group $i$ not
recei/e acupuncture treat'ent for 1 9eeks
after ran$o'isation& fro' 9eek 0 the,
recei/e$ 1: sessions of the acupuncture
treat'ent $escri(e$ a(o/e6 *n all treat'ent
groups, patients 9ere allo9e$ to treat
osteoarthritis knee pain 9ith oral non7
steroi$al anti7in8a''ator, $rugs if
necessar,6 ?he use of other pain
treat'ents, such as $rugs acting through
the central ner/ous s,ste', or
corticosteroi$s, 9as not allo9e$6
Patients 9ere infor'e$ a(out
acupuncture an$ 'ini'al acupuncture in
the stu$, as follo9s) FI*n this stu$,,
$ifferent t,pes of acupuncture 9ill (e
co'pare$6 3ne t,pe is si'ilar to the
acupuncture treat'ent use$ in China6 ?he
other t,pe $oes not follo9 these principles,
(ut has also (een associate$ 9ith positi/e
outco'es in clinical stu$ies6FJ
10,11%ll patients co'plete$ stan$ar$ 4uestionnaires at
(aseline, an$ after 1 9eeks, :D 9eeks, an$ =: 9eeks6
?he Arst 4uestionnaire 9as $istri(ute$ to the patients (,
the stu$, ph,sician an$ co'plete$ (efore the start of
treat'ent ((aseline)6 Patients sent their co'plete$
4uestionnaires to the stu$, ofAce in seale$ en/elopes6
<ollo97up 4uestionnaires 9ere sent to all patients (, the
stu$, ofAce6 ?he pri'ar, outco'e 'easure 9as the
Western 3ntario an$ McMasters !ni/ersities
3steoarthritis *n$eE6*n cases of (ilateral osteoarthritis,
the knee $eAne$ at (aseline as 'os
tPatients <ollo97upBaseline assess'entassess'ent
Ph,sicians Me$ical status?reat'ent $ocu'entation
0 1
Ni#ure 1: Stud$
desi#n<ollo97up
assess'ent
:D<ollo97up
assess'ent
=:
Wee
k0%cupuncture treat'ent 9as se'i7
stan$ar$ise$) all patients 9ere treate$ 9ith
a selection of local an$ $istant points
chosen (, the acupuncturists accor$ing to
the principles of tra$itional Chinese
'e$icine6 %$$itional points inclu$e$ (o$,
acupuncture points, ear acupuncture
points, an$ trigger points6 Patients 9ere
treate$ (, use of at least siE local
acupuncture points fro' the follo9ing
selection)sto'ach ;>, ;=, ;D& spleen 0, 10&
(la$$er >0& ki$ne, 10& gall (la$$er ;;, ;>&
li/er 1& eEtraor$inar, points e$ing, Ki,an6
%$$itionall,, ph,sicians selecte$ an$
nee$le$ at least t9o $istant points fro' the
follo9ing selection) spleen >, =, D& sto'ach
D& (la$$er :0, =B, =1, D0, D:& ki$ne, ;6
Sterile $isposa(le one7ti'e nee$les ha$ to
(e use$, (ut ph,sicians 9ere a(le to
choose the nee$le length an$ $ia'eter6
Ph,sicians 9ere instructe$ to achie/e $e
4i (an irra$iating feeling $ee'e$ to in$icate
effecti/
e
nee$lin
g) if
possi(l
e, an$
nee$le
s 9ere
sti'ula
te$
'anual
l, at
least
once
$uring
each
sessio
n6%cupu
ncture 1:
sessions
Waiting
list
control
(no
acupun
cture)%
cupunct
ure 1:
session
s<ollo97
up
<ollo97
u
pCan$o'isationMini'al acupuncture 1: sessions <ollo97up
9996thelancet6co' Mol 366 Ful$ E 2005 13?
Articles
1:painful 9as the one assesse$ throughout
the entire stu$,6 <urther'ore, the patient
4uestionnaire inclu$e$ a 'o$iAe$ /ersion
of the 2er'an Societ, for the Stu$, of
Pain sur/e,,1;9hich uses the 2er'an
/ersion of the pain $isa(ilit, in$eE&1>a scale
for assessing e'otional aspects of pain
(Sch'er@e'pAn$ungs7Skala LS+SM)&1=the
$epression scale (%llge'eine
Depressionsskala L%DSM)&
1100
patie
nts
asse
sse$
for
eligi(
ilit,
D:0 not
interest
e$ after
receipt
of
infor'a
tion
or
o(/iou
s
/iolatio
n of
selectio
n
criteria
>
1
0

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;00 ran$o'ise$an$ the 2er'an /ersion of the S<7
;D1B1D(M3S;D7ite' short for' 4ualit,7of7life 4uestionnaire)to
assess healthrelate$ 4ualit, of life6 %$$itionall,, se/eral
4uestions on socio$e'ographic characteristics, nu'erical
rating scales for pain intensit,, 4uestions a(out 9ork$a,s
lost, an$ glo(al assess'ents 9ere aske$6 ?he nu'(er of
$a,s 9ith pain an$ 'e$ication 9ere $ocu'ente$ in a $iar,
(, the patients6 Blin$ing to treat'ent an$ the cre$i(ilit, of
the treat'ent 'etho$ 9ere assesse$ (, the patients 9ith a
cre$i(ilit, 4uestionnaireafter the thir$ acupuncture session6
%t the en$ of the stu$,, patients 9ere aske$
9hether the, thought the, ha$ recei/e$
acupuncture follo9ing the principles of
Chinese 'e$icine or the other t,pe of
acupuncture6 Ph,sicians $ocu'ente$ 'e$ical
histor,, acupuncture treat'ent, serious
a$/erse e/ents, an$ si$e7effects for each
session6 Patients also reporte$ si$e7effects at
the en$ of 9eek 16
Statistical anal$si
s 1=0 allocate$ acupuncture
1 9ithout (aseline an$ acupuncture ; lost to follo97up after ran$o'isation

B;
foll
o9
e$
up
at
1
9e
eks

B;
foll
o9
e$
up
at
:D
9e
eks

B1
foll
o9
e$
up
at
=:
9e
eks
B= in
*??
population
(all
inclu$e$
in
sensiti/it,
anal,sis
9ith
'issing
/alues
replace$)
1 9ithout
(aseline
a 10 /iolation of treat'ent protocol 1> other protocol
$e/iations 1: /iolation of treat'ent protocol B other
protocol $e/iations
s
Articles
/otal :n=2E4< Acu"uncture :n=14E< Minimal acu"uncture
:n=?5< 7aitin# list :n=?0< Wo'en 10= (DDN) 10= (B0N) >0 (D=N) >1 (=0N)
Men 00 (;>N) >> (;0N) :D (;=N) :0 (>1N) %ge (,ears) D>FG0 (DFG=) D>FG= (DFG>) D;FG> (DFGD)
D;FGD (DFGB) Bo$,7'ass in$eE :0FG0 (=FG0) :0FG= (>FG1) :1FG1 (>FGD) :1FG; (=FG10) 10 ,ears of
school >; (1DN) 1D (11N) 11 (1BN) 1D (:>N) "ellgren criteria
"ellgren 0 1 (0FG;N) 0 0 1 (1N) "ellgren 1 1= (=N) D (>N) = (BN) > (DN) "ellgren : 1:1 (>1N)
=: (;=N) :0 (;0N) >0 (=BN) "ellgren ; 1:0 (>1N) DD (>>N) ;: (>;N) :: (;1N) "ellgren > ;B
(1;N) := (1BN) 0 (1:N) ; (>N)
Duration of $isease (,ears) 0FG: (BFG0) 0FG1 (1FG=) 0FG0 (BFGD) 1FG1 (DFG1) Da,s per 'onth 9ith
pain :DFG: (DFG=) :DFG: (DFG=) :DFGD (DFG>) :=FGB (DFG1) 3steoarthritis (ilateral ::> (BDN) 110
(B>N) =1 (BBN) =D (10N) Pre/ious treat'ent
Phar'aceutical inter/ention 0B (;;N) >; (:0N) :B (;DN) :B (;0N) (past D 'onths)
Ph,siotherap, (past D 'onths) >= (1=N) :: (1=N) B (0N) 1D (:;N) Pre/ious acupuncture
treat'ent :; (1N) 1> (0N) = (BN) > (DN)
%/erage pain (O%S) D=FG; (1>FG=) D>FG0 (1>FG:) D1FG= (1>FG>) D:FG1 (1=FG0) W3M%C *n$eE =1FG>
(11FGB) =0FG1 (11FG1) =:FG= (11FGD) =1FGD (11FG1) Disa(ilit, (PD*) :1FG0 (1;FG:) :BFG0 (1>FG:)
:BFG1 (1;FG:) :1FG; (11FG;) Ph,sical health (S<7;D)P :0FGB (BFGB) ;0FG0 (BFG>) :0FG: (1FG:) :0FG1
(BFG0) Mental health (S<7;D)P =1FG; (1:FG0) =1FG1 (1:FG1) =1FG1 (11FGD) =0FGD (1:FG1) Pain
affecti/e (S+S, tstan$ar$ scores) >1FG0 (0FG1) >1FG1 (0FG;) >0FG: (1FGB) >1FG1 (0FG;) Pain sensoric
(S+S, tstan$ar$ scores) =:FGB (0FG0) =:FG> (0FG=) =>FG1 (10FG1) =:FG0 (10FG0) Depression (%DS, t
stan$ar$ scores) =1FG: (0FG>) =1FG: (10FG0) =1FG; (BFG0) =1FG: (0FG>)
Data are nu'(er (N) or 'ean (SD)6 W3M%CQ4uestionnaire for assessing pain, function an$ stiffness $ue to osteoarthritis (Western 3ntario an$ McMasters
!ni/ersities 3steoarthritis *n$eE)& O%SQ/isual analogue scale& PD*Qpain $isa(ilit, in$eE& S<7;DQM3S ;D7ite' short7for' 4ualit,7of7life 4uestionnaire&
S+SQ4uestionnaire for assessing the e'otional aspects of pain (Sch'er@e'pAn$ungsskala)& %DSQ$epression scale (%llge'eine Depressionsskala)6
Pigher /alues in$icate (etter status
6/a5le 1: +aseline c&aracteristics
of intention>to>treat "o"ulation
-ole of t&e fundin#
source
:Acu"uncture
Minimal "
acu"uncture
Cre$i(ilit, after thir$ session nQ1>1 nQB; *'pro/e'ent
eEpecte$ =FG: (1FG1) =FG1 (0FG0) 0FG1D0
Ceco''en$ation to others =FG= (1FG0) =FGD (0FGB)
0FG;1> ?reat'ent logical =FG0 (1FG;) >FG1 (1FG;) 0FG;:B
+ffecti/e also for other $iseases =FGD (0FG0) =FGB (0FGD)
0FGD01
2uess at en$ of 9eek =: nQ1>D nQB1 0FG;;: FIChinese
acupunctureFJ 0D (DDN) >0 (=DN) FI?he other t,pe of
acupunctureFJ 0 (DN) > (DN) FIDonFHt kno9FJ >1 (:1N)
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1 Ni#ure 4: Scatter "lots of t&e 7BMAC indeC at 5aseline and at 3ee' @ Soli$ lines represent parallel linear regression an$
$otte$ lines represent anal,sis of co/ariance (>=FRline)6 Patients on the >=FRline ha/e no change in W3M%C score, 9hereas those
a(o/e an$ (elo9 in$icate (etter an$ 9orse con$ition, respecti/el,6
participate in the stu$,6 <igure : sho9s the trial
proAle6 3f ;00 patients ran$o'ise$ siE9ere eEclu$e$
fro' the intention7to7treat population (ecause no
(aseline $ata 9ere a/aila(le, an$ the, $i$ not
recei/e the stu$, inter/ention6 %ll the re'aining :0>
patients treate$ in a total of :1 outpatient centres
9ere inclu$e$ in the intention7to7treat population6
?hree patients in the acupuncture group (one
planne$ operation, one car acci$ent, one reason
unclear) an$ three in the 'ini'al acupuncture group
(one 'o/e$ to another to9n, t9o reason unclear)
stoppe$ the acupuncture treat'ent pre'aturel,6
%fter 1 9eeks, $ata for the 'ain efAcac, anal,sis
9ere a/aila(le for :1= (0BN) patients6 ?he
perprotocol anal,sis inclu$e$ ::>patients6
%ll patients ha$ pre/iousl, (een treate$ 9ith
analgesics6 0= (;:N) ha$ recei/e$ acupuncture in
the past (1N for osteoarthritis) an$ :D1 (11N)
patients eEpecte$ a su(stantial i'pro/e'ent fro'
acupuncturetreat'ent6 ?a(le 1 sho9s the (aseline
characteristics of patients in the three stu$,
groups6 Patients in the acupuncture group 9ere
treate$ 9ith a 'ean of 1B (SD 1) nee$les an$
patients in the 'ini'al acupuncture group 9ith a
'ean of 1: (;) nee$les6 ?he a/erage $uration of
sessions 9as a(out ;0 'in in (oth groups6 %ll
patients in the acupuncture group 9ere treate$ at
local an$ $istant points& a$$itional points 9ere
use$ in D00 (;=N) treat'ent sessions an$ trigger
points in :>D (1>N) treat'ent sessions6 %fter
three treat'ent sessions, patients rate$ the
cre$i(ilit, of acupuncture an$ 'ini'al
acupuncture 'uch the sa'e an$ as /er, high,
an$ at the en$ of the stu$, 'ost patients (elie/e$
that the, ha$ recei/e$ acupuncture follo9ing the
principles of Chinese 'e$icine (ta(le :)6 <igure ;
sho9s the $e/elop'ent of the 'ean W3M%C
in$eE score6 ?he 'ean (aseline7a$5uste$
W3M%C in$eE at the en$ of 9eek 1 9as :DFG0
(S+ 1FG>) in th
e9rimar$ outcome Acu"uncture mean :S!< Minimal acu"uncture 7aitin# list Acu"uncture *s minimal " Acu"uncture
*s " mean :S!< mean :S!< acu"unctureO :E5JCI< 3aitin# list O :E5JCI<
Puestionnaire W3M%C *n$eE :DFG0 (1FG>) ;=FG1 (1FG0) >0FGD (:FG0) -C1FG1 (-C1;FG= to -C>FG:) 0FG001 -C::FGB (-C:BFG= to
-C1BFG0) 0FG001 W3M%C Pain :>FG> (1FG>) ;;FG: (:FG0) >>FG0 (:FG1) -C1FG1 (-C1;FGB to -C;FG0) 0FG001 -C:0FG= (-C:=FG= to
-C1=FG=) 0FG001 W3M%C Stiffness ;:FGB (1FG0) >:FG; (:FGB) ==FG0 (:FG1) -C0FGD (-C1DFG0 to -C;FG:) 0FG00; -C::FG; (-C:1FG0
to -C1=FGB) 0FG001 W3M%C Ph,sical function :BFG0 (1FG>) ;=FG1 (:FG0) =0FG> (:FG1) -C1FG0 (-C1;FGB to -C>FG0) 0FG001 -C:;FG>
(-C:1FG> to -C11FG>) 0FG001 Disa(ilit, (PD*) 1DFG> (0FG0) ::FG: (1FG:) :BFG> (1FG;) -C=FG1 (-C1FG1 to -C:FG1) 0FG001 -C11FG0
(-C1>FG1 to -CBFG0) 0FG001 Ph,sical health (S<-C;D)S ;DFG: (0FGD) ;;FG1 (0FG1) ;1FG1 (0FG0) ;FG1 (1FG1 to =FG1) 0FG00; >FG>
(:FG; to DFG=) 0FG001 Mental health (S<-C;D)S =;FGD (0FGB) =1FG0 (1FG0) =0FGB (1FG0) 1FGB (-C0FGD to >FG0) 0FG1;B :FG0 (0FGD to
=FG;) 0FG01D Pain affecti/e (S+S, tstan$ar$ scores) >:FG> (0FGB) >>FG1 (0FG0) >=FG0 (1FG0) -C1FGB (-C;FG0 to 0FG=) 0FG1;>
-C;FG= (-C=FG1 to -C1FG:) 0FG00; Pain sensoric (S+S, tstan$ar$ scores) >BFG; (0FGB) >1FG1 (1FG0) >0FG1 (1FG0) -C0FG1 (-C;FG: to
1FGD) 0FG>0> -C:FG= (-C=FG0 to -C0FG1) 0FG0>> Depression (%DS, tstan$ar$ scores) >BFG0 (0FG1) >1FG; (1FG1) >0FG> (1FG1)
-C0FG= (-C;FG1 to :FG1) 0FGB:= -C1FG= (-C>FG1 to 1FG1) 0FG:=0 Da,s 9ith li'ite$ function 1DFG; (1FG=) :1FG; (:FG1) :BFG> (:FG:)
-C>FG0 (-C10FG1 to 0FG:) 0FG0=0 -C11FG1 (-C1DFG; to -C=FG1) 0FG001 .iar$ Da,s 9ith pain in 9eek 1 ($iar,) >FG> (0FG:) =FG;
(0FG;) DFG> (0FG;) -C1FG0 (-C1FGD to -C0FG;) 0FG00= -C:FG1 (-C:FG1 to -C1FG>) 0FG001 Da,s 9ith 'e$ication in 9eeks =-C1
($iar,) >FG= (0FG=) >FGD (0FGD) =FG1 (0FGB) -C0FG1 (-C1FGD to 1FG=) 0FG0:: -C1FG; (-C;FG0 to 0FG;) 0FG110
W3M%CQ4uestionnaire for assessing pain, function, an$ stiffness $ue to osteoarthritis (Western 3ntario an$ McMasters !ni/ersities 3steoarthritis
*n$eE)& PD*Qpain $isa(ilit, in$eE& S<7;DQM3S ;D7ite' short7for' 4ualit,7oflife 4uestionnaire& S+SQ4uestionnaire for assessing the e'otional aspects of
pain (Sch'er@e'pAn$ungsskala)& %DSQ$epression scale (%llge'eine Depressionsskala)6 PMean (aseline7a$5uste$ treat'ent $ifference (et9een
groups6 Sigher /alues in$icate (etter status
/a5le 3: 9rimar$ and secondar$ outcomes at t&e end of 3ee' @
140 9996thelancet6co' Mol 366 Ful$ E 200
5
sacupuncture group co'pare$ 9ith ;=FG1 (1FG0) in
the 'ini'al acupuncture group an$ >0FGD (:FG0) in
the 9aiting list group (treat'ent $ifference)
acupuncture vs 'ini'al acupuncture -C1FG1 L0=N C*
-C1;FG= to -C>FG:M, pQ0FG000:& acupuncture
vs9aiting list -C::FGB L-C:BFG= to -C1BFG0M,
p0FG0001)6 <igure > sho9s the treat'ent effect for
in$i/i$ual patients categorise$ 9ith respect to
treat'ent group6 ?he results 9ere /er, si'ilar if
'issing /alues 9ere replace$ an$ if (aseline /alues
9ere entere$ in the anal,sis of co/ariance as
co/ariates6 %$$itionall,, the per7protocol anal,sis
sho9e$ closel, si'ilar results6
Patients 9ho recei/e$ acupuncture ha$ signiAcantl,
(etter results for al'ost all secon$ar, outco'e
'easures than $i$ those in the 'ini'al acupuncture
an$ 9aiting list groups6 ?he proportion of respon$ers
(patients 9ith a $ecrease of at least =0N in their
W3M%C in$eE score) 9as =:N in the acupuncture
group co'pare$ 9ith :1N in the 'ini'al
acupuncture group an$ ;N in the 9aiting list group
(all patients 9ith no $ata 9ere counte$ as
nonrespon$ers)6 3n all W3M%C su(scales (pain,
stiffness, an$ ph,sical function), the acupuncture
group sho9e$ signiAcant i'pro/e'ents co'pare$
9ith the 'ini'al acupuncture an$ the 9aiting list
groups (ta(le ;)6 When 9eeks 1 an$ 1 9ere
co'pare$, the 'ean nu'(er of $a,s per 9eek 9ith
intake of analgesics $ecrease$ in the acupuncture
group (fro' 1FG> L:FG:M to 0FG0 L:FG0M) an$ in the
'ini'al acupuncture group (fro' 1FG= L:FGDM to 1FG1
L:FG;M), 9hereas in the 9aiting list control group this
nu'(er re'aine$ closel, si'ilar (1FG1 L:FG;M vs1FG0
L:FGDM)6 %$$itionall,, the percentage of patients using
analgesics in the acupuncture an$ 'ini'al
acupuncture groups $ecrease$ (et9een 9eeks 1 an$
1 (fro' >:N to ::N an$ fro' ;1N to :;N,
respecti/el,), 9hereas in the 9aiting list group there
9as onl, a s'all change (fro' =:N to >=N)6 ?he
i'pro/e'ents recor$e$ after 1 9eeks in the
acupuncture an$ 'ini'al acupuncture groups
persiste$ $uring the follo97up perio$, although the
$ifferences(et9een the groups 9ere no longer
signiAcant after :D or =: 9eeks (pQ0FG0D; an$
0FG010 fro' eEplorator, anal,ses& ta(le >)6 ?he
patients in the 9aiting list group 9ho recei/e$
acupuncture (et9een 9eeks 0 an$ 1D sho9e$
i'pro/e'ents after treat'ent that 9ere si'ilar to
those reporte$ in the original acupuncture group
(W3M%C in$eE $ecrease$ fro' =1FGD L11FG1M to
;1FGD L:0FGDM)6
During the :D 9eeks after ran$o'isation, a total of
nine serious a$/erse e/ents (three acupuncture, t9o
'ini'al acupuncture, four 9aiting list) 9ere
$ocu'ente$6 3ne patient fro' the 'ini'al
acupuncture group $ie$ fro' ',ocar$ial infarction6
W3M
%C at
(aseli
ne
%ll cases 9ere a$'itte$ to hospital an$ regar$e$ as
unrelate$ to the stu$, con$ition or the inter/ention6
:>si$e7effects 9ere reporte$ (, :0 (1>N) patients in
the acupuncture group (11 s'all hae'ato'a or
(lee$ing an$ siE other si$e7effects, such as nee$ling
pain), an$ 1D si$e7effects (, 1; (11N) patients
(pQ0FG>10) in the 'ini'al acupuncture group (nine
s'all hae'ato'a or (lee$ing, one case of local
in8a''ation at the nee$ling site, an$ siE other si$e7
effects)6
.iscussion
*n this stu$,, patients 9ith osteoarthritis of the knee
9ho recei/e$ acupuncture ha$ signiAcantl, less pain
an$ (etter function after 1 9eeks than $i$ patients
9ho recei/e$ 'ini'al acupuncture or no
acupuncture6 %fter :D an$ =: 9eeks, eEplorator,
anal,sis in$icate$ that the $ifferences (et9een
acupuncture an$ 'ini'al acupuncture 9ere no
longer signiAcant6
1?he present stu$, is, to $ate, one of the largest an$
'ost rigorous trials of the efAcac, of acupuncture
a/aila(le6 *ts strengths inclu$e a prepu(lishe$
protocol,
:0,:1inter/entions (ase$ on eEpert consensus (,
4ualiAe$ an$ eEperience$ 'e$ical acupuncturists,
assess'ent of the cre$i(ilit, of inter/entions,
outco'e 'easure'ents as reco''en$e$ in
gui$elines for trials on osteoarthritis,an$ /er, high
follo97up rates6 3n
e9996thelancet6co' Mol 366 Ful$ E 2005 141
inter/entions6:0-C;:
;:
:0
;0*n three of these trials,;0-C;:
;
5
Private practices) C %''an, Berlin& M %nger'eier, Bergen&
C %@cona, attingen& J Bach'ann, attingen& % Behren$t,
Pots$a'& " Be,er, Do(ra& C Birn(au', Bergisch 2la$(ach&
B Brinkhaus, Berlin& S B-Tcker, Berlin& Daute,
#-T$enschei$& C D-Thn, Oetschau& % 2ha@i7*$rissi, Walluf& P
e, M-Tnchen& C7 e'pen, M-Tnchen& M er'ans,
+uskirchen& C err'ann, Markto(er$orf& J u''els(erger,
M-Tnchen& C u,er, Markto(er$orf& % Jung, Berlin& J
"leinhen@, Walluf& S "okott, Cott(us& %7M "ronse$er,
M-Tnchen& * "ulescho9a, Berlin& #eonhar$,, M-Tnchen& B
#in$er, Berlin& % Miet@ner, Berlin& CNUgel, M-Tnchen&
#Schi''el, Ba'(erg& B Schlaak, Berlin& +Sp-Tntrup,
Walluf& !Stiegler, Berlin& Vanping Wu, Berlin, M Wen@el,
Ba'(erg6 Randomisation centres) *nstitute for Me$ical
Statistics an$ +pi$e'iolog,, ?echnische !ni/ersitWt
M-Tnchen, Munich (" "lein, % Bockel(rink, J2eiger, " Xick,
P anel, Baurecht, J Bertra', C oll9eck, P#e9in)6
Nundin# Stu$, acti/ities at the *nstitute for Social
Me$icine, +pi$e'iolog, an$ ealth +cono'ics, Berlin
9ere fun$e$ (, the follo9ing social health insurance fun$s)
?echniker "rankenkasse, B"" %ktir, Betrie(skrankenkasse
$er %llian@ 2esellschaften, Bertels'ann B"", Bosch B"",
B"" BMW, Dai'lerChr,sler B"", B"" Deutsche Bank,
<or$ Betrie(skrankenkasse, B"" oechst, ,po
Oereins(ank Betrie(skrankenkasse, Sie'ens7
Betrie(skrankenkasse, an$elskrankenkasse,
*nnungskrankenkasse a'(urg6 Stu$, acti/ities at the
Centre for Co'ple'entar, Me$icine Cesearch, Munich
9ere fun$e$ (, the follo9ing social health insurance fun$s)
Deutsche %ngestellten7"rankenkasse& Bar'er
+rsat@kasse& "auf'Wnnische "rankenkasse& a'(urg7
M-Tnchener "rankenkasse& anseatische "rankenkasse&
2'-Tn$er +rsat@kasse& X" "rankenkasse f-Tr Bau7 un$
ol@(erufe& Br-Thler +rsat@kasse& "rankenkasse +intracht
eusensta''& an$ Buch$rucker "rankenkasse6
ConQict of interest statement
We $eclare that 9e ha/e no
con8ict of interest6
Ac'no3led#ments We 9oul$ like to thank D *rnich,
Depart'ent of %naesthesiolog,, #u$9ig7MaEi'ilians7
!ni/ersit,, Munich, an$ M a''es, Depart'ent of
Neurolog,, ?echnische !ni/ersitWt, Munich for $e/eloping
the acupuncture treat'ent protocols together 9ith J
u''els(erger, an$ for their input at /arious le/els of the
protocol $e/elop'ent& an$ "Wegschei$er, *nstitute of
Statistics an$ +cono'etrics, !ni/ersit, of a'(urg, an$ %
Neiss, *nstitute of Me$ical Statistics an$ +pi$e'iolog,,
?echnische !ni/ersitWt, Munich for statistical a$/ice6
-eferences 1 Crea'er P, och(erg MC6
3steoarthritis6 Lancet 100B&350:
=0;-C006 : ?ra'er MC, Moore C%, Ce,nol$s DJ,
McYua, J6 Yuantitati/e
esti'ation of rare a$/erse e/ents 9hich follo9 a
(iological progression) a ne9 'o$el applie$ to
chronic NS%*D use6 Pain :000&@5: 1D0-C1:6
; %non6 Ceco''en$ations for the 'e$ical 'anage'ent
of osteoarthritis of the hip an$ knee) :000 up$ate6
%'erican College of Cheu'atolog, Su(co''ittee on
3steoarthritis 2ui$elines6 Arthritis Rheum :000&43:
100=-C1=6
> +isen(erg DM, Da/is CB, +ttner S#, et al6 ?ren$s in
alternati/e 'e$icine use in the !nite$ States,
1000-C100B) results of a follo9up national sur/e,6 JAMA
1001&2@0: 1=D0-CB=6
= +@@o J, a$ha@, O, Birch S, et al6 %cupuncture for
osteoarthritis of the knee) a s,ste'atic re/ie96 Arthritis Rheum :001&44:
110-C:=6
D "ellgren J6 Ca$iolocical %ssess'ent of 3steo7%rthrosis6
AnnRheum Dis 10=B&16: >0>-C=0:6
B "essler S, 2uenther "P, Puhl W6 Scoring pre/alence an$ se/erit, in
gonarthritis) the suita(ilit, of the "ellgren Z #a9rence scale6 Clin
Rheumatol 1001&1?: :0=-C006
1 Brinkhaus B, Becker7Witt C, Jena S, et al6 %cupuncture Can$o'i@e$
?rials (%C?) in patients 9ith chronic lo9 (ack pain an$ osteoarthritis of the
knee) $esign an$ protocols6 Forsch Komplementarmed Klass Naturheilkd
:00;&10: 11=-C016
0 Dea$'an P, %l7
"hafa5i M6 % 'anual of
acupuncture6 SusseE,
!") Journal of Chinese
Me$icine Pu(lications,
:0016
10 Bella', N, Buchanan WW,
2ol$s'ith C, Ca'p(ell J, Stitt
#W6 Oali$ation stu$, of W3M%C) a
health status instru'ent for
'easuring clinicall, i'portant
patient rele/ant outco'es to
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patients 9ith osteoarthritis of the
hip or knee6 J Rheumatol 1011&15:
11;;-C>06
11 Stucki 2, Meier D, Stucki S, et
al6 +/aluation of a 2er'an /ersion
of W3M%C (Western 3ntario an$
McMaster !ni/ersities) %rthrosis
*n$eE6 Z Rheumatol 100D&55:
>0-C>06
1: NagelB, 2er(ershagen!,
#in$ena2, PAngstenM6 +nt9ickling
un$ e'pirische -T(erpr-Tfung $es
Deutschen Sch'er@frage(ogens
$er D2SS6 Schmer:00:& 16:
:D;-CB06
1; Dill'ann !, Nilges P, Saile ,
2er(ershagen !6
Behin$erungseinschWt@ung (ei
chronischen Sch'er@patienten6
Schmer 100>& 100-C106
1> 2eissner +S%6 Die
Sch'er@e'pAn$ungsskala (S+S)6
2Uttingen) ogrefe, 100D6
1= aut@inger M, Bailer M6
%llge'eine Depressionsskala
(%DS)6 Die $eutsche Oersion $es
C+S7D6 Weinhei') Belt@, 100;6
1D Bullinger M,
"irch(erger *6 S<7;D
<rage(ogen @u'
2esun$heits@ustan$6
2Uttingen) ogrefe,
10016
1B Oincent C6 Cre$i(ilit,
assess'ents in trials of
acupuncture6 Complement
Med Res 1000&4: 1-C116
11 Oickers %J, %lt'an D26 Statistics
notes) %nal,sing controlle$ trials 9ith
(aseline an$ follo9 up 'easure'ents6 !MJ :001&323:
11:;-C:>6
10 Ber'an BM, Singh BB, #ao #, et al6 % ran$o'i@e$
trial of acupuncture as an a$5uncti/e therap, in
osteoarthritis of the knee6 Rheumatolo"#
$%&'ord(1000&3@: ;>D-C=>6
:0 %lt'an C, Bran$t ", och(erg M, et al6 Design
an$ con$uct of clinical trials in patients 9ith
osteoarthritis) reco''en$ations fro' a task force
of the 3steoarthritis Cesearch Societ,6 Cesults
fro' a 9orkshop6 %steoarthritis Cartila"e 100D&4:
:1B-C>;6
:1 Bella', N, "ir9an J, Boers M, et al6
Ceco''en$ations for a core set of outco'e
'easures for future phase *** clinical trials in knee, hip,
an$ han$ osteoarthritis6 Consensus $e/elop'ent at
3M+C%C? ***6 J Rheumatol 100B&24: B00-C10:6
:: #in$e ", Dincer <6 o9 infor'e$ is consent in
sha'7controlle$ trials of acupuncture[ J Altern
Complement Med:00>&10: ;B0-C1=6
:; White %C, a,hoe S, art %, +rnst +6 Sur/e, of
%$/erse e/ents follo9ing %cupuncture ( S%<% )) a
prospecti/e stu$, of ;: 000 consultations6
Depart'ent of Co'ple'entar, Me$icine,
!ni/ersit, of +Eeter, +Eeter, !", :001) 1-C:06
:> Melchart D, Wei$enha''er W, Streng %, et al6
Prospecti/e in/estigation of a$/erse effects of
acupuncture in 0BB;; patients6 Arch )ntern Med
:00>&164: 10>-C0=6
:= Va'ashita , ?suka,a'a , ori N, "i'ura
?, ?anno V6 *nci$ence of a$/erse reactions
associate$ 9ith acupuncture6 JAltern
Complement Med :000&6: ;>=-C=06
:D Ber'an BM, Singh BB, #ao #, et al6 % ran$o'i@e$
trial of acupuncture as an a$5uncti/e therap, in
osteoarthritis of the knee6 Rheumatolo"#
$%&'ord(1000&3@: ;>D-C=>6
:B Christensen BO, #uhl *!, Oil(ek , Bulo9 ,
Drei5er NC, Cas'ussen <6 %cupuncture treat'ent
of se/ere knee osteoarthrosis) a long7ter' stu$,6
Acta Anaesthesiol Scand 100:& 36: =10-C:=6
:1 ?illu %, ?illu S, Oo9ler S6 +ffect of acupuncture on
knee function in a$/ance$ osteoarthritis of the knee)
a prospecti/e, nonran$o'ise$ controlle$ stu$,6
Acupunct Med :00:&20: 10-C:16
:0 ?ake$a W, Wessel J6 %cupuncture for the
treat'ent of pain of osteoarthritic knees6 Arthritis
Care Res 100>&?: 111-C::6
;0 Mols(erger %, BU9ing 2, Jensen "!, #orek M6
Sch'er@therapie 'it %kupunktur (ei 2onarthrose6
Der Schmer 100>&@: ;B-C>:6
;1 Petrou P, Winkler O, 2enti 2, Balint 26 Dou(le (lin$
trial to e/aluate the effect of acupuncture treat'ent on
knee osteoarthritis6 Scand J Acupunct 1011&3:
11:-C1=6
;: Sang$ee C, ?eekachunhatean S, Sananpanich
", et al6 +lectroacupuncture /ersus $iclofenac in
s,'pto'atic treat'ent ofosteoarthritis of the knee)
a ran$o'i@e$ controlle$ trial6 !MCComplement
Altern Med :00:&2: ;6
;; Oincent C, #e9ith 26 Place(o controls for acupuncture stu$ies6 JRSoc
Med 100=&@@: 100-C:0:
69996thelancet6co' Mol 366 Ful$ E 2005 143