reviewarticle update on the clinical effect of acupuncture...

Review ArticleUpdate on the Clinical Effect of AcupunctureTherapy in Patients with Gouty Arthritis: SystematicReview and Meta-Analysis

Wei-wei Lu, Jin-ming Zhang, Zheng-tao Lv, and An-min Chen

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, Hubei 430030, China

Correspondence should be addressed to An-min Chen; [email protected]

Received 17 May 2016; Revised 1 August 2016; Accepted 24 August 2016

Academic Editor: Deborah A. Kennedy

Copyright © 2016 Wei-wei Lu et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective. The aim of this study is to evaluate the clinical efficacy and safety of acupuncture therapy in the treatment of acutegouty arthritis. Methods. A literature search of PubMed, EMBASE, ISI Web of Science, CENTRAL, and CNKI was conductedfrom the inception date of each database up to October 2015. Two investigators screened each article independently and wereblinded to the findings of the other reviewer. Data was extracted according to the predetermined collection form. Meta-analysiswas performed. Results. We analyzed data from 28 RCTs involving 2237 patients with gouty arthritis. Compared with conventionalpharmacological treatments acupuncture was more effective in rendering patients free from symptoms after 24 hours, loweringserum urate, alleviating pain associated with gouty arthritis, and decreasing the ESR; regarding CRP, no statistically significantdifference was found. In addition, the frequency of adverse events in acupuncture treatment was lower than that in controlgroup. Conclusion. Based on the findings of our study, we cautiously suggest that acupuncture is an effective and safe therapy forpatients with gouty arthritis. However, the potential beneficial effect of acupuncturemight be overstated due to the methodologicaldeficiency of included studies. High quality RCTs with larger scale are encouraged.

1. Introduction

Gouty arthritis is a disorder of purine metabolism and resultsfrom monosodium urate (MSU) crystal deposition in andaround the joints caused by longstanding hyperuricaemia,which is defined as a serum uric acid (sUA) concentrationexceeding the limit of sUA solubility (6.8mg/dL) [1, 2]. Thischronic inflammatory condition ismediated byMSU crystalsand characterized by recurrent attacks of monoarthritisor polyarthritis [3]. Gouty arthritis is the most prevalentinflammatory arthritis in developed countries, especiallyin elder men; and the incidence was reported to increaseover the past 20 years [4]. Quality of life is impairedduring intercritical periods and during flares in addition toassociated comorbidities such as obesity, diabetes mellitus,hypertension, hyperlipidaemia, and chronic renal disease[5–7]. Without proper treatment, acute gouty arthritis canprogress into a chronic, deforming, and physically disabling

disease through the development of tophi, joint destruction,and persistent pain [8, 9].

The American College of Rheumatology (ACR) andEuropean League Against Rheumatism (EULAR) guidelinesfor the pharmacologic management of acute gouty arthri-tis include oral colchicine, nonsteroidal anti-inflammatorydrugs (NSAIDs), and corticosteroids [10, 11]. However, theside effects associated with pharmacological agents restricttheir long-term use. Some authors have pointed out thatmanagement of gouty arthritis is often suboptimal and thatflares are inevitable, necessitating better strategies to handleattacks [12].

Complementary and alternative medicine (CAM) iswidely advocated to face the increasing demand for nonphar-macological approaches. As a mainstream of CAM therapy,acupuncture based on traditional Chinese medicine (TCM)theory has been commonly used for the treatment of goutyarthritis in Chinese cultures. A previous systematic review

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2016, Article ID 9451670, 14 pageshttp://dx.doi.org/10.1155/2016/9451670

2 Evidence-Based Complementary and Alternative Medicine

had reported the clinical effect of acupuncture in relievingpain and decreasing serum uric acid, whereas only tenRCTs were included, the heterogeneity among studies wasnot discussed, and the security of acupuncture therapy wasnot confirmed [13]. Recently, new literatures to evaluatethe efficacy and safety of acupuncture therapy for goutyarthritis are emerging. Therefore, an updated meta-analysisis required.

2. Methods

This systematic review was conducted in accordance with thePreferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [14].

2.1. Search Strategy. A comprehensive literature search ofPubMed, EMBASE, CENTRAL, ISI Web of Science, andCNKI was conducted. All the above databases were searchedfrom their inception dates up to the latest issue (October2015), without language restriction. Medical subject headings(MeSH) and free text words were combined to retrieve allthe potential studies. MeSH were modified based on thespecifications of each database. The following search strategywas used for the literature search in PubMed, CENTRAL,and ISI Web of Science: (“Gout” or Gout or gouts) and(“Acupuncture Therapy” or acupuncture or moxibustionor acupoint or acupressure or acustimulation). For CNKI,search terms were “Zhen” and “Tongfeng”. In addition, thebibliographies of relevant systematic reviews and clinicalguidelines were manually searched. The reference section foreach study was also searched.

2.2. Types of Participants. To be included in our system-atic review, the enrolled subjects had to be diagnosed asgouty arthritis according to ascertained diagnostic criteria:European League Against Rheumatism (EULAR) criteria,the American Rheumatism Association (ARA) preliminaryclassification criteria for acute gout 1977 [15], Mexico 2010[16], Netherland 2010 [17], or the Criteria of Diagnosis andTherapeutic Effect of Diseases and Syndromes in TCM issuedby the State Administration of TCM [18]. No restrictions onrace, age, and sex were imposed.

2.3. Interventions. Patients in experimental groups mainlyreceived acupuncture therapy (including manual acupunc-ture and electroacupuncture), either alone or in combina-tion with pharmacological treatment or TCM treatment,without differentiating different acupuncture techniques,acupoints selection, or needle materials. Patients in con-trol groups were treated with western medicine (includingcolchicine, allopurinol, indomethacin, benzbromarone, cele-coxib, probenecid, meloxicam, and ibuprofen); no specifictypes of drugs were imposed.

2.4. Outcome Measurements. The primary outcome measurewas clinical effect and the frequency of adverse events inboth groups; the secondary outcomemeasurements includedclinical parameters associated with acute gouty arthritis, suchas serum uric acid, pain intensity using visual analogue scale

(VAS), erythrocyte sedimentation rate (ESR), and C-reactiveprotein (CRP).

2.5. Types of Publication. The included studies were requiredto be randomized controlled trials aiming to assess theefficacy of acupuncture therapy for gouty arthritis. Articlesregarding animal experiments, reviews articles, case reports,or expert experience reports were excluded.

2.6. Data Extraction. Two investigators (Wei-wei Lu and Jin-ming Zhang) screened each article independently and wereblinded to the findings of the other reviewer. According to thepredetermined inclusion criteria, two reviewers performedstrict screening to identify qualified articles independently,and they extracted data from these eligible articles usinga standardized data collection form, which included firstauthor, year of the publication, study design, baseline char-acteristics for participants in different groups, diagnosticcriteria of gouty arthritis, interventions and control treat-ment, main outcome assessments, duration of treatments,and adverse events.

Any disagreement between the two reviewers wasresolved through discussion until a consensus was reached.The third review author (Jin-ming Zhang) was consulted if aconsensus could not be reached.

2.7. Quality Assessment. Cochrane Collaboration’s tool wasutilized to assess the risk of bias in the selected RCTs,which was based on seven items: random sequence gen-eration, allocation concealment, blinding of participantsand personnel, blinding of outcome assessment, incompleteoutcome data, selective reporting, and other sources ofbias [19]. Two reviewers assessed the risk of bias amongstudies independently; the results were compared afterwards.Disagreements regarding the risk of bias assessment weresettled by discussion and consensus between reviewers.

2.8. Data Synthesis and Analysis. The enrolled participantswere dichotomized into being cured and not cured to expressthe intervention effect. Odds ratio (OR) and the associated95% confidence intervals (CIs) were calculated for clinicaleffect and frequency of adverse events. The mean difference(MD) for changes from baseline in the continuous variableswas calculated using the same methodology. Random effectmodel was employed for meta-analysis, since the homo-geneity of the included studies could not be guaranteed.The chi-squared test and the Higgins 𝐼2 test were used toassess the heterogeneity among studies (𝑃 > 0.1 and 𝐼2indicate acceptable heterogeneity). Forest plot and funnel plotwere generated via RevMan 5.3 (Copenhagen: the NordicCochrane Centre, the Cochrane Collaboration, 2014).

Metaregression was performed using Stata version 12.0(StataCorp LP, USA) to find the possible source of het-erogeneity, such as acupuncture type, treatment duration,and whether combined with other therapy. Begg’s rankcorrelation test and Egger’s linear regression test were used toevaluate the publication bias if the number of included studieswas greater than ten.

Evidence-Based Complementary and Alternative Medicine 3

3. Results

3.1. Literature Search Results. An initial search of RCTsyielded 379 potential literature citations, including 27 fromPubMed, 8 from CENTRAL, 57 from EMBASE, 30 from ISIWeb of Science, 255 from CNKI, and additional two recordsfromother sources. 47 articleswere deleted because theywereduplicates for retrieving. According to the prespecified inclu-sion criteria, 66 potentially relevant studies were selectedand retrieved for a full-text assessment after reading theirtitles and abstracts. Of the remaining 66 studies, two weredeleted because they were non-RCTs, two were duplicatesfor publication, one study did not provide available data,and 33 studies employed uncomfortable intervention. A totalof 28 studies [20–47] were deemed eligible for inclusion inthis review. The literature screening process is presented in aflowchart in Figure 1.

3.2. Study Characteristics. The main characteristics ofincluded studies are summarized in Table 1. The 28 studiesincluded a total of 1174 patients in acupuncture group and1063 patients in control group. Subjects were diagnosed asgouty arthritis according to either the criteria stipulated byUS Rheumatology Association or the criteria stipulated byState Administration of TCM. The age of enrolled subjectsranged from 18 to 80 years. All the studies were conductedby Chinese investigators in a single center and publishedbetween 2002 and 2015. Clinical efficacy of acupuncture wasevaluated by all studies, but only ten of them analyzed thesafety in both groups.

Patients in acupuncture group received manual acupunc-ture or electroacupuncture; the acupoints selection was basedonTCMmeridian theory.The acupuncture was applied aloneor in combination with other treatment, such as Chineseherbal medicine, acupoint injection, and local blocking ther-apy. Acupuncture therapy was administered daily or everytwo days, the needles were retained for 20 to 30 minutes foreach session, and the treatment course ranged from 5 days to28 days. The detailed information is listed in Table 2.

3.3. Quality Assessment. The risk of bias among studies wasassessed using Cochrane Collaboration’s tool. All studiesincluded the suggested randomization, half of the studies[22, 28, 29, 34–38, 41–43, 45–47] reported the methodof random sequence generation, and five studies [24, 27,30, 31, 39] were judged to high risk of bias because thepatients were arranged according to their registration order.No study reported detail about allocation concealment. Theblinding of outcome assessment was judged to unclear riskof bias because no studies mentioned blinding of outcomeassessment. The blinding of participants and personnel wasjudged to high risk of bias as it was impossible to carry outin our included studies. When it comes to incomplete data,only four studies [27, 34, 41, 47] provided the number ofdropouts and reason for withdrawal. All the studies reportedthe prespecified outcomemeasurements. Baseline similaritiesseemed to be achieved by each study: no statistical differenceswere detected in age, gender, or symptom duration. Fivestudies [24, 27, 30, 31, 39] were judged to high risk of bias

while the other 23 were unclear risk of bias. Judgementsabout each risk of bias item for each included study weresummarized in Figures 2 and 3.

3.4. Clinical Effect. All the included studies employed clinicaleffect as outcome assessment; the therapeutic effect wasevaluated in accordance with the Criteria of Diagnosis andTherapeutic Effect of Diseases and Syndromes in TCM issuedby the State Administration of TCM in 1994 [18].The patientswere defined as complete resolution of acute attack when thejoints swelling, pain, and redness disappeared with normallaboratory indices 24 hours after the treatment, improvedwhen symptoms and signs alleviated with laboratory indicesimproved, or failed when the symptoms and laboratoryindices did not have improvement. Thus, the patients inexperimental and control groups were dichotomized as com-plete resolution and not completely resolved; OR and 95%CI in each study were calculated based upon the raw data.The combined effects of 28 individual studies showed thatacupuncture therapy could further improve the clinical curerate compared with western medicine (OR 2.71; 95% CI 2.22,3.32; 𝑃 < 0.00001); the results of heterogeneity test indicatedno obvious heterogeneity (𝑃 = 0.24, 𝐼2 = 15%) (Figure 4).

3.5. Uric Acid. Twenty-two studies [20, 25–39, 41–43, 45–47]measured blood uric acid as outcome; changes from baselinewere calculated. Data extracted from 22 individual studiesshowed that heterogeneity existed (𝑃 < 0.00001, 𝐼2 = 85.1%);random effects model was utilized for statistical analysis.Pooled data suggested that acupuncture therapy could furtherdecrease uric acid than western pharmacological treatment(MD 41.30; 95% CI 24.86, 57.74; 𝑃 < 0.00001) (Figure 5).

3.6. Pain Intensity (VAS Score). Seven studies [29, 33, 34, 41,43, 46, 47] that measured pain intensity using VAS scorewere identified. Data extracted showed obvious heterogeneityin the consistency of study results (𝑃 < 0.00001, 𝐼2 =94%); random effects model was employed. Among theseven studies, six found that acupuncture therapy couldfurther improve the VAS score than pharmacological therapy,whereas Liu et al. reported an opposite result. The com-bination of results showed that acupuncture could furtherimprove pain associated with acute gouty arthritis (MD 1.92;95% CI 0.96, 2.87; 𝑃 < 0.0001) (Figure 6).

3.7. ESR. Five studies [25, 30, 33, 34, 43] reported onESR; only one study found statistically significant differenceregarding the decrease of ESR in acupuncture group andcontrol group. The heterogeneity was acceptable (𝑃 = 0.25,𝐼2= 26%); the pooled data showed that acupuncture therapy

was better than western medicine in decreasing ESR (MD1.75; 95% CI 0.11, 3.38; 𝑃 = 0.04) (Figure 7).

3.8. CRP. Four studies [25, 30, 33, 34] measured CRP asoutcome; statistically significant difference was detected inonly one study. No obvious heterogeneity was found (𝑃 =0.23, 𝐼2 = 30%); the combined data showed no significantdifference in decreasing CRP between acupuncture and


PubMed = 27

EMBASE = 57

ISI Web of Science = 30

CENTRAL = 8

Additional records identifiedthrough other sources (n = 2)

Totally identified (n = 379)

Records after the duplicateswere removed (n = 332)

Records excluded(n = 266)

Full-text articles excluded,with reasons (n = 38)

Non-RCT = 2

Duplicates = 2

Unavailable data = 1

Uncomfortableintervention = 33

Full-text articlesassessed for eligibility

(n = 66)

Studies included inqualitative synthesis

(n = 28)

Studies included inquantitative synthesis

(meta-analysis)(n = 28)

CNKI = 255

Duplicates (n = 47)

Figure 1: Flow diagram of the literature selection.


Table1:Ch

aracteris

ticso

fRCT

sidentified

intheliteraturesearch.

Stud

yPo

pulatio

n(E/C

)Age

(meanor

range)

Diagn

ostic

criteria

Outcomem

easurements

Adversee

vents

Baiyin

2014

[20]

43/44

E:27–56;C:

28–54

ARA

1977

Clinicaleffect,uricacid

NR

Chenle2015

[21]

25/25

E:25–58;C:

23–6

0ARA

1977

Clinicaleffect

NR

Gon

gandCh

en2014

[22]

60/60

NR

ARA

1977

Clinicaleffect

NR

Gui

andCh

en2014

[23]

32/28

E:28–6

5;C:

26–6

2SA

TCM

1994

Clinicaleffect

Yes

Hee

tal.2008

[24]

30/30

E:28–6

7;C:

30–6

5SA

TCM

1994

Clinicaleffect

Yes

Huetal.2010[25]

68/60

E:45.42±11.46

;C:46.74±11.22

ARA

1977

Clinicaleffect,uricacid,C

RP,E

SRYes

Jinetal.2012[26]

30/30

E:23-67;C:

25–6

6ARA

1977


Yes

Lietal.2013[27]

31/29

E:49.67±19.3;C

:46.52±10.29

ARA

1977


Yes

Liuetal.200

8[28]

56/44

E:34–70:C:

33–74

SATC

M1994


NR

Liuetal.2014[29]

44/41

E:20–50;C:

18–52

ARA

1977

Clinicaleffect,uricacid,V

ASscore

Yes

Liu2014

[30]

87/87

E:44

.1;C:

43.4

ARA

1977


RP,E

SRYes

Ma2

002[31]

48/30

E:31–78;C:

29–72

ARA

1977


NR

Ma2

004[32]

42/30

E:31–78;C:

29–72

ARA

1977


NR

Wang2013

[33]

40/20

E:23–70;C:

23–70

ARA

1977

Clinicaleffect,ES

R,CR

P,uricacid

Yes

Wuetal.2012[34]

34/32

E:32–6

0;C:

33–6

3SA

TCM

1994


RP,E

SR,V

ASscore

NR

Xietal.200

6[35]

66/64

E:50.1±5.2;C:

45.1±6.1

ARA

1977


ASscore

NR

Xiee

tal.2007

[36]

30/30/30

E:40

–70;C1

:42–69;C

2:43–7

1ARA

1977


NR

Xiee

tal.2009

[37]

30/30

E:32–6

5;C:

40–6

7SA

TCM

1994


Yes

Yan2009

[38]

40/20

E:35–75;C:

38–76

ARA

1977


Yes

Yinetal.200

5[39]

40/30/30

E1:36–

72:E2:31–6

9:C:

34–76

SATC

M1994


NR

Zhang2010

[40]

28/29

E:38–79;C:

29–80

SATC

M1994

Clinicaleffect

NR

Zhao

2007

[41]

30/30

E:31–6

8;C:

30–70

SATC

M1994


ASscore

NR

Zhao

etal.200

9[42]

30/30

E:33–70;C:

32–7

1ARA

1977


NR

Zhou

etal.2012[43]

80/80

E:36–6

5;C:

37–6

4SA

TCM

1994


ASscore,ES

RNR

Zhou

2014

[44]

20/20

E:18–4

8;C:

17–50

SATC

M1994

Clinicaleffect

NR

Zong

etal.2011[45]

20/20

E:34–72;C:

30–70

ARA

1977


NR

Zouetal.200

6[46]

30/30/30

E1:32–70;E

2:31–72;C:

35–7

1SA

TCM

1994


ASscore

NR

Zouetal.200

7[47]

30/30

E:32–70;C:

31–72

SATC

M1994


ASscore

NR

Note.E:experim

ent;C:

control;N

R:no

treported;CR

P:C-

reactiv

eprotein;ESR

:erythrocytesedimentatio

nrate;TCM

:traditio

nalC

hinesemedicine;VA

S:visualanalogue

scale;ARA

1977:the

American

Rheumatism

Associatio

nprelim

inaryclassifi

catio

ncriteria

fora

cute

gout

1977;SAT

CM1994:the

Criteria

ofDiagn

osisandTh

erapeutic

Effecto

fDise

ases

andSynd

romes

inTradition

alCh

ineseMedicineissuedby

theState

Administratio

nof

Tradition

alCh

ineseM

edicine.

6 Evidence-Based Complementary and Alternative MedicineTa

ble2:Detailsof

interventio

nin

acup

unctureg

roup

sand

controlgroup

s.Stud

yAc

upun

ctureintervention

Con

trol

Duration

Baiyin

2014

[20]

MA(A

ship

oint)2

5min,oncea

day,plus

Chineseh

erbalm

edicine

Colchicine0

.5mgtwicea

day,

allopu

rinol50

mgtwicea

day

15days

Chenle2015

[21]

MA(A

ship

oint,G

b34,Sp10,St35,EX

-LE4

,S34,E

X13)

25min,oncea

day,plus

Chineseh

erbal

medicine

Colchicine0

.5mgtwicea

day,

allopu

rinol50

mgtwicea

day

15days

Gon

gandCh

en2014

[22]

MA(A

ship

oint),everyo

ther

day

Allo

purin

ol50

mg3tim

esad

ay20

days

Gui

andCh

en2014

[23]

MA(A

ship

oint,Sp9,St36,Sp6,Li11,

Gv14),oncea

day,plus

Chineseh

erbalm

edicine

Allo

purin

ol100m

g3tim

esad

ay,

colchicine

0.5m

g/ho

ur10

days

Hee

tal.2008

[24]

EA(A

ship

oint,St36,Sp6,Ki3,Sp4)

20min,oncea

day,plus

acup

oint

injection

Colchicine0

.5mg3tim

esad

ay,

indo

metacin

25mg3tim

esad

ay10

days

Huetal.2010[25]

MA(G

b11,Cv

6,Ki3,B4

0)30

min,oncea

day,plus

Chineseh

erbalm

edicine

Indo

metacin

25mg3tim

esad

ay,

allopu

rinol100m

g3tim

esad

ay21

days

Jinetal.2012[26]

MA(Sp6

,Sp9,L

i11,S34,Sp10,H3,L15),oncea

day,plus

Chineseh

erbalm

edicine

Allo

purin

ol100m

gtwicea

day

7days

Lietal.2013[27]

MA(Sp6

,St36,Sp9,St40

,Sp10,Li11,

Li4,Lr3)

15min,oncea

day,plus

Chineseh

erbalm

edicine

Colchicine0

.5mg3tim

esad

ay21

days

Liuetal.200

8[28]

EA(A

ship

oint,Sp1,L

r3,Sp6

,St40,Sp9,Gb34)

30min,oncea

day,plus

localblockingtherapy

Allo

purin

ol100m

g3tim

esad

ay,

indo

metacin

25mg3tim

esad

ay7days

Liuetal.2014[29]

MA(surroun

dedthed

iseased

region

),on

cead

ay,pluse

xternalC

hinese

herbalmedicine

Colchicine0

.5mgtwicea

day,

celecoxib200m

gtwicea

day

7days

Liu2014

[30]

MA(Sp10,Sp6,St36,St40,Sp9,Li11,

Li4,Lr3)

30min,oncea

day,plus

Chineseh

erbalm

edicine

Benzbrom

aron

e50m

gon

cead

ay14

days

Ma2

002[31]

MA(Sp6

,Ki3,Sp10,Li11)3

0min,oncea

day

Indo

metacin

25mg3tim

esad

ay,

allopu

rinol100m

g2-3tim

esad

ay28

days

Ma2

004[32]

MA(Bl23,Bl22,C

v3,C

v4,Sp10,Sp6,Ki3)

30min,oncea

day

Allo

purin

ol100m

g2-3tim

esad

ay28

days

Wang2013

[33]

MA(A

ship

oint,K

i3,Sp9,B

60,Li11,L

i4,L

r3)2

0min,oncea

day,plus

Chineseh

erbalm

edicine

Colchicine0

.5mg3tim

esad

ay14

days

Wuetal.2012[34]

EA2H

z(St36,St40,Aship

oint)3

0min,oncea

day,plus

bloo

dlettin

gColchicine0

.5mg3tim

esad

ay,

allopu

rinol100m

g3tim

esad

ay6days

Xietal.200

6[35]

MA(A

ship

oint,Sp6

,Sp10,Sp9,Li4,Li11)

30min,oncea

day

Meloxicam

7.5mgon

cead

ay20

days

Xiee

tal.2007

[36]

EA(Sp6

,Sp9,St40)

30min,oncea

day

Allo

purin

ol100m

g3tim

esad

ay,

prob

enecid

250m

g3tim

esad

ay10

days

Xiee

tal.2009

[37]

MA(surroun

dedthed

iseased

region

)30m

in,oncea

day

Allo

purin

ol100m

g3tim

esad

ay,

indo

metacin

25mg3tim

esad

ay15

days

Yan2009

[38]

MA(A

ship

oint,K

i3,Sp6

,St36,B6

0,St40

,Lr3)3

0min,oncea

day,plus

bloo

dlettin

gAllo

purin

ol100m

gtwicea

day

14days

Yinetal.200

5[39]

EA(St36,St40

,Aship

oint)3

0min,oncea

day;EA

plus

weste

rnmedicine

Allo

purin

ol100m

g3tim

esad

ay,

indo

metacin

25mg3tim

esad

ay6days

Zhang2010

[40]

MA30

min,oncea

day,plus

weste

rnmedicine

Indo

metacin

25mg3tim

esad

ay6days

Zhao

2007

[41]

MA(St36,Sp6,Aship

oint),on

cead

ayIndo

metacin

25mg3tim

esad

ay,

allopu

rinol100m

g3tim

esad

ay6days

Zhao

etal.200

9[42]

EA(A

ship

oint,Li4,St36,Gb34,Sp10,B

60,K

i3)3

0min,oncea

day,plus

bloo

dlettin

gProb

enecid

250m

gtwicea

day

10days

Zhou

etal.2012[43]

MA(Sp10,St36,Sp6

,Li11,G

b34)

30min,oncea

day,plus

infrared

irradiatio

nIndo

metacin

25mg3tim

esad

ay5d

ays

Zhou

2014

[44]

MA(A

ship

oint,Li11,Sp10,Sp6,Gv14,Lr3,St36)3

0min,oncea

day,plus

Chineseh

erbalm

edicine

Ibup

rofen300m

gtwicea

day

7days

Zong

etal.2011[45]

MA(A

ship

oint,Sp9,St36,Sp6,Li11,L

i4,S34)3

0min,oncea

day,plus

moxa-moxibustio

nAllo

purin

ol100m

g3tim

esad

ay,

indo

metacin

25mg3tim

esad

ay6days

Zouetal.200

6[46]

EA100H

z(St36,Sp6

)30m

in,oncea

day;EA

2Hz(

St36,Sp6

)30m

in,oncea

day

Allo

purin

ol100m

g3tim

esad

ay,

indo

metacin

25mg3tim

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Ma 2004

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Figure 2: Risk of bias summary: review authors’ judgements about each risk of bias item for each included study.


Random sequence generation (selection bias)

Allocation concealment (selection bias)

Blinding of participants and personnel (performance bias)

Blinding of outcome assessment (detection bias)

Incomplete outcome data (attrition bias)

Selective reporting (reporting bias)

Other bias

0 25 50 75 100

Low risk of biasUnclear risk of biasHigh risk of bias

(%)

Figure 3: Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.

control therapy (MD −0.26; 95% CI −1.42, 0.90; 𝑃 = 0.66)(Figure 8).

3.9. Adverse Events. Among the included studies, ten [23–27, 29, 30, 33, 37, 38] reported adverse events associatedwith acupuncture or western medicine. The reported adverseevents mainly included gastrointestinal tract reaction, centralnervous system reaction, leukopenia, skin rash, and faintingduring acupuncture treatment. Except two studies [26, 38],eight studies found a higher prevalence of adverse events inthe control group than that in the acupuncture group. Thepooled OR showed a statistically significant lower risk ofadverse events in acupuncture group when compared withwestern medicine (OR 0.08, 95% CI 0.03, 0.23; 𝐼2 = 34%)(Figure 9).

3.10. Metaregression. Metaregression was conducted byresidual (restricted) maximum likelihood (REML) withKnapp-Hartung modification. Three possible factors thatmay contribute to heterogeneity among studies were tested:acupuncture type (manual acupuncture or electroacupunc-ture), combined therapy (whether the patients were treatedwith acupuncture alone or combined with other treatment),and duration of treatment (within a week or longer than aweek). The results of metaregression were listed in Table 3.Combined therapy and duration of treatment were notstatistically correlated with the heterogeneity in uric acid orVAS score. Acupuncture type administered could explain20.20% and 23.55% of the heterogeneity in uric acid and VASscore, respectively. However, the correspondence betweenacupuncture type and heterogeneity within VAS score didnot reach a statistical difference.

3.11. Publication Bias. Publication biases were presented byfunnel plots (Figures 10 and 11), and the resulting graphs showno obvious asymmetry for clinical effect and uric acid. Begg’stest (clinical effect: 𝑧 = 0.86, 𝑃 = 0.392; uric acid: 𝑧 = 0.94,

𝑃 = 0.346) andEgger’s test (clinical effect: 𝑡 = 1.00,𝑃 = 0.325;uric acid: 𝑡 = 0.46, 𝑃 = 0.650) also indicated no statisticallysignificant publication bias.

4. Discussion

Our current study analyzed data from28RCTs involving 2237patients that aimed to assess the therapeutic effect and safetyof acupuncture for gouty arthritis. Based on the findings ofour study, acupuncture could further improve the clinicaleffective rate and decrease uric acid and VAS score whencompared with western medicine. The risk of adverse eventswas significantly lower in acupuncture group. Regarding thedecrease in CRP and ESR, the results remain debatable.

The application of different acupuncture modalities bydifferent investigators can greatly affect curative effect ofacupuncture therapy [48]. The acupuncture proceduresshould be performed according to syndromes differentiationbased on TCM theory. In the selected studies, acupunctureintervention was administered alone [22, 31, 32, 35–37, 41,46] or in combination with other therapies, which includedChinese herbal medicine [20, 21, 23, 25–27, 29, 30, 33, 44],acupoint injection [24, 47], local blocking therapy [28],bloodletting [34, 38, 42], infrared irradiation [43], moxa-moxibustion [45], and western medicine [39, 40]. Regardlessof the type of the additional therapy, acupuncture therapywas mainly received in experimental groups. The acupointselection was inconsistent among included studies; never-theless, Sp6, St36, and Ashi point were the most commonlyused acupoint. In our present study, data was combinedwithout differentiating acupoint selection and acupuncturetechniques. Thus, the results indicate an overall clinicalefficacy and definite conclusion could not be drawn.

Gouty arthritis is one of themost common indications forwhich patients seek complementary and alternative medicinetreatment, even though the use of CAM was relatively low,compared with reported rates of between 28% and 90% in


Study or subgroup

Baiyin 2014Chenle 2015Gong and Chen 2014Gui and Chen 2014He et al. 2008Hu et al. 2010Jin et al. 2012Li et al. 2013Liu et al. 2008Liu et al. 2014Liu 2014Ma 2002Ma 2004Wang 2013Wu et al. 2012Xi et al. 2006Xie et al. 2007Xie et al. 2007Xie et al. 2009Yan 2009Yin et al. 2005Yin et al. 2005Zhang 2010Zhao 2007Zhao et al. 2009Zhou et al. 2012Zhou 2014Zong et al. 2011Zou et al. 2006Zou et al. 2007

Total (95% CI)

Total events

Events

371133112237112029415621191314371818202215262

1116428

171114

652

Total

432560323068303156448748424034663030304030402830308020203030

1204

Events

126

108

17206

1118324910667

146

10117

1212179

184

1057

351

Total

442560283060302944418730302032643030302030302930308020203030

1093

Weight

3.0%2.5%4.5%2.9%3.0%5.9%2.6%3.2%5.0%1.9%7.4%3.8%3.0%2.6%3.0%5.3%2.7%3.1%3.1%2.9%3.3%3.6%0.6%2.8%3.1%6.3%1.9%1.7%2.5%2.9%

100.0%

M-H, random, 95% CI

16.44 [5.54, 48.82]2.49 [0.74, 8.35]

6.11 [2.62, 14.27]1.31 [0.44, 3.92]2.10 [0.71, 6.22]2.39 [1.16, 4.90]2.32 [0.72, 7.41]2.98 [1.04, 8.51]1.55 [0.70, 3.44]

3.84 [0.96, 15.37]1.40 [0.76, 2.58]1.56 [0.60, 4.02]3.30 [1.12, 9.74]1.12 [0.35, 3.59]2.50 [0.85, 7.37]4.56 [2.12, 9.81]

6.00 [1.89, 19.04]3.00 [1.05, 8.60]3.45 [1.19, 9.99]2.27 [0.75, 6.89]1.50 [0.54, 4.17]2.79 [1.05, 7.40]

2.15 [0.18, 25.19]1.90 [0.62, 5.86]2.67 [0.92, 7.70]3.81 [1.92, 7.55]

2.67 [0.65, 10.97]5.67 [1.25, 25.61]2.89 [0.86, 9.74]2.88 [0.95, 8.72]

2.71 [2.22, 3.32]

Acupuncture Western medicine Odds ratio Odds ratio

M-H, random, 95% CI

0.02 0.1 1 10 50Favours control Favours acupuncture

Heterogeneity: 𝜏2 = 0.05; 𝜒2 = 34.02, df = 29 (P = 0.24); I2 = 15%

Test for overall effect: Z = 9.72 (P < 0.00001)

Figure 4: Forest plot of acupuncture therapy versus western medicine: clinical effect.

patients with rheumatoid arthritis (RA) and more than 80%in those with osteoarthritis (OA) [49, 50].The goal of therapyin an acute gout attack is prompt and safe termination of painand inflammation [51]. Our results suggest that acupuncturetherapy could further improve pain when compared withwestern medicine, but, in terms of inflammation attenuation,the results remain debatable.

When treating gouty arthritis one needs to treat acuteattacks and lower excess stores of uric acid to achievedissolution of monosodium urate crystals through a long-term reduction of serum uric acid concentrations far beyond

the threshold for saturation of urate and provide prophylaxisto prevent acute flares [52]. In addition to the improvementin pain-relief and clinical effect, acupuncture therapy couldfurther decrease uric acid, compared with conventional west-ern pharmacological therapy. The underlying mechanismof this urate-lowering effect was still unclear, which needsto be further investigated. To analyze the possible sourceof heterogeneity within these studies, metaregression wasperformed.The type of acupuncture therapy was proved to besignificantly correlated with the heterogeneity; the evidencethus suggests that the urate-lowering effects of manual


Study or subgroup

Baiyin 2014Hu et al. 2010Jin et al. 2012Li et al. 2013Liu et al. 2008Liu et al. 2014Liu 2014Ma 2002Ma 2004Wang 2013Wu et al. 2012Xi et al. 2006Xie et al. 2007Xie et al. 2007Xie et al. 2009Yan 2009Yin et al. 2005Yin et al. 2005Zhao 2007Zhao et al. 2009Zhou et al. 2012Zong et al. 2011Zou et al. 2006Zou et al. 2007

Total (95% CI)

Mean275.2

244.8581.7217

162.86220.16189.56148.1

149.1169.51

184.08330.788.6688.66

223.08206

221.98189.06109.82109.82

88.3134.82128.25119.26

SD59.47

102.4673.0762.2

46.4746.1

77.9261.3359.9949.68

108.84166.0464.1864.18

6184.6661.4454.5884.1884.1863.4284.54

8395.08

Total436830315644874842403466303030404030303080203030

1009

Mean165.2

202.9736.6

185.68126.5

162.53193.5763.1437.2128.34

148.92100.56

57.881.03176204

224.03224.0377.1780.1766.9

87.17136.8876.76

SD57.8690.0770.2

66.5947.4743.9372.9186.0585.7322.03

104.67180.8267.3264.0377.5479.7765.9965.9975.3975.3996.1174.6994.0862.95

Total446030294441873030203264303030203030303080203030

901

Weight

4.6%4.2%4.1%4.3%4.8%4.8%4.7%4.2%4.1%4.8%3.4%3.1%4.2%4.3%4.2%3.8%4.4%4.4%3.9%3.9%4.6%3.5%3.7%3.9%

100.0%

IV, random, 95% CI110.00 [85.34, 134.66]

41.88 [8.53, 75.23]45.10 [8.84, 81.36]

31.32 [−1.34, 63.98]36.36 [17.79, 54.93]57.63 [38.49, 76.77]−4.01 [−26.43, 18.41]84.96 [49.62, 120.30]

111.90 [76.26, 147.54]41.17 [23.00, 59.34]

35.16 [−16.35, 86.67]230.14 [170.41, 289.87]

30.86 [−2.42, 64.14]7.63 [−24.81, 40.07]47.08 [11.78, 82.38]2.00 [−41.71, 45.71]−2.05 [−32.38, 28.28]−34.97 [−65.61, −4.33]

32.65 [−7.79, 73.09]29.65 [−10.79, 70.09]21.40 [−3.83, 46.63]47.65 [−1.79, 97.09]−8.63 [−53.52, 36.26]

42.50 [1.70, 83.30]

41.30 [24.86, 57.74]

Acupuncture Western medicine Mean difference Mean difference

IV, random, 95% CI

−500 −250 0 250 500Favours control Favours acupuncture

Heterogeneity: 𝜏2 = 1367.30; 𝜒2 = 154.86, df = 23 (P < 0.00001); I2 = 85%


Figure 5: Forest plot of acupuncture therapy versus western medicine: uric acid.

acupuncture and electroacupuncture are somewhat different.No conclusions can be drawn as to which acupuncture typeis superior for patients with gouty arthritis.

A previous systematic review [13] consisting of tenRCTs reported that acupuncture alone was more effectivein the improvement of pain and uric acid when comparedwith standard western medicine. However, only ten studieswere identified to be eligible; only VAS score and uricacid were analyzed as outcome. No data about the safetyof acupuncture therapy was provided. In addition, tworecords listed in Figure 1A of the previous systematic reviewwere miscalculated, although this would not influence thefinal conclusion drawn by their work [13]. Based on fiverequired domains (study limitations, consistency, directness,precision, and publication bias), Shekelle and colleaguesassessed the strength of evidence for the conclusions drawnby the aforementioned systematic review [53]. The strengthof evidence for conclusions was judged to be insufficientto support or refute the effectiveness of acupuncture onsymptomatic outcomes, partially due to the unreportedpublication bias. Our meta-analysis managed to summarizeall published RCTs to compare the clinical effect and safety of

acupuncture with those of western medicine. 28 RCTs wereidentified; clinical effect, VAS score, uric acid, ESR, CRP, andadverse events were combined; risk of bias was independentlyassessed by two experienced reviewers using Cochrane’s tool.The results ofmetaregression showed a significant correlationbetween acupuncture type and heterogeneity in uric acid;publication bias assessment indicates no obvious publicationbias. Regarding the safety of acupuncture, which is an obviousadvantage of CAM therapies, the overall incidence of adverseevents in acupuncture groups was significantly lower thanthat in western medicine group.

There are several limitations in our study. First, themethodological qualities of included studies were judgedto be poor; details about allocation concealment were notdescribed by any study, which might limit the value ofconclusion about the clinical efficacy and safety of acupunc-ture. Second, all included studies utilized western medicineas control treatment, making the blinding of participantsimpossible. A sham acupuncture control is preferable, asopposed tomedication or no intervention. Also, the majorityof selected studies were written in Chinese, which limits thedissemination of scientific researches on acupuncture. Future


Study or subgroup

Liu et al. 2014Wang 2013Wu et al. 2012Zhao 2007Zhou et al. 2012Zou et al. 2006Zou et al. 2007

Total (95% CI)

Mean4.434.826.646.696.466.576.56

SD1.420.581.371.511.6

1.511.55

Total44403430803030

288

Mean4.664.294.183.8

4.273.7

3.71

SD1.610.791.381.611.7

1.461.52

Total41203230803030

263

Weight

14.3%14.9%14.3%13.9%14.7%14.0%13.9%

100.0%

IV, random, 95% CI−0.23 [−0.88, 0.42]

0.53 [0.14, 0.92]2.46 [1.80, 3.12]2.89 [2.10, 3.68]2.19 [1.68, 2.70]2.87 [2.12, 3.62]2.85 [2.07, 3.63]

1.92 [0.96, 2.87]


IV, random, 95% CI


Heterogeneity: 𝜏2 = 1.54; 𝜒2 = 102.20, df = 6 (P < 0.00001); I2 = 94%


Figure 6: Forest plot of acupuncture therapy versus western medicine: pain intensity (VAS score).

Study or subgroup

Hu et al. 2010Liu 2014Wang 2013Wu et al. 2012Zhou et al. 2012

Total (95% CI)

Mean28.3

51.9711.0915.4527.7

SD14.0516.933.42

10.547.28

Total6887403480

309

Mean29

49.249.84

16.1623.8

SD16.0321.692.559.188.29

Total6087203280

279

Weight

8.6%7.2%

45.4%10.2%28.6%

100.0%

IV, random, 95% CI−0.70 [−5.95, 4.55]2.73 [−3.05, 8.51]1.25 [−0.29, 2.79]−0.71 [−5.47, 4.05]

3.90 [1.48, 6.32]

1.75 [0.11, 3.38]


IV, random, 95% CI



Test for overall effect: Z = 2.09 (P = 0.04)

Figure 7: Forest plot of acupuncture therapy versus western medicine: ESR.

Study or subgroup

Hu et al. 2010Liu 2014Wang 2013Wu et al. 2012

Total (95% CI)

Mean15.4817.3822.943.63

SD13.086.646.21.2

Total68874034

229

Mean12.5118.0321.824.41

SD11.837.935.021.45

Total60872032

199

Weight

6.6%20.5%13.0%60.0%

100.0%

IV, random, 95% CI2.97 [−1.35, 7.29]−0.65 [−2.82, 1.52]1.12 [−1.80, 4.04]

−0.78 [−1.42, −0.14]

−0.26 [−1.42, 0.90]


IV, random, 95% CI



Test for overall effect: Z = 0.44 (P = 0.66)

Figure 8: Forest plot of acupuncture therapy versus western medicine: CRP.

studies within western context are required. Third, financialconsiderations are important for consumers choosing CAMoptions as expensive treatments are generally avoided andcost is a frequent reason to stop treatment [54]. In Chineseculture, the safety and cost-effectiveness of acupuncturetherapy could assure the compliance of patients. Consideringparticipants’ opinions, cost-effectiveness of acupuncture alsomeant its efficacy. However, only ten studies recorded adverse

events associated with acupuncture and routine care; nostudy included cost-effectiveness assessment. Last, accordingto the ACR guideline, choice of pharmacologic agents shouldbe based upon number of joints involved and pain intensity;the established pharmacologic ULT should be continuedwithout interruption. However, some of our included stud-ies only administered first-line therapy options (NSAIDs,corticosteroids, and colchicine); ULT therapy during acute


Study or subgroup

Gui and Chen 2014He et al. 2008Hu et al. 2010Jin et al. 2012Li et al. 2013Liu et al. 2014Liu 2014Wang 2013Xie et al. 2009Yan 2009

Total (95% CI)

Total events

Events1000001004

6

Total32306830314487403040

432

Events1513406268

142

70

Total28306030294187203020

375

Weight

14.0%9.4%9.2%

9.3%8.6%

13.9%9.3%9.5%

16.8%

100.0%

M-H, random, 95% CI0.03 [0.00, 0.23]0.02 [0.00, 0.38]0.09 [0.00, 1.74]Not estimable

0.06 [0.00, 1.07]0.18 [0.01, 3.81]0.16 [0.02, 1.33]0.02 [0.00, 0.34]0.02 [0.00, 0.33]1.00 [0.17, 5.98]

0.08 [0.03, 0.23]

Acupuncture Western medicine Odds ratio Odds ratio

M-H, random, 95% CI

0.001 0.1 1 10 1000Favours acupuncture Favours control



Figure 9: Forest plot of acupuncture therapy versus western medicine: adverse events.

Table 3: Metaregression of basic characteristics of trials and improvement of uric acid and VAS score.

Outcome Number of RCTs Factor tested 𝑡 𝑃 Adjusted 𝑅2

Uric acid 22Acupuncture type 2.21 0.038 20.20%Combined therapy 0.35 0.730 −6.31%

Duration of treatment 1.58 0.127 7.67%

VAS score 7Acupuncture type −1.62 0.165 23.55%Combined therapy 1.32 0.243 12.20%

Duration of treatment −1.27 0.259 10.11%Note. RCT: randomized controlled trial; VAS: visual analogue scale.

0.02 0.1 1 10 50

0

0.5

1

1.5

2

OR

SE(lo

g[O

R])

Figure 10: Funnel plot of acupuncture therapy versus westernmedicine: clinical effect.

attack was stopped; some studies only used ULT, withoutusing first-line pharmacologic options. This would lead to anexaggeration of conclusions; thus, the effect of interventionshould be interpreted cautiously.

−500 −250 0 250 500

0

10

20

30

40

50

MD

SE(M

D)

Figure 11: Funnel plot of acupuncture therapy versus westernmedicine: uric acid.

In summary, the findings of our current study suggestthat acupuncture is better in improving clinical effectiverate, decreasing uric acid, and VAS score compared withwestern medicine. The overall incidence of adverse events in


acupuncture group was lower than that in western medicinegroup. Due to the methodological deficiency of included tri-als, acupuncture therapy could not be guaranteed as standardCAM treatment. Additional RCTs with rigorous design andlarger sample size are encouraged.

Competing Interests

The authors have declared no conflict of interests.

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