Inflammatory bowel diseases (IBD) encompass a group of chronic nonspecific inflammatory diseases of the bowel with unknown aetiology. The main forms of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). UC and CD are similar with regard to their clinical manifestations, diagnosis, and treatment. Clinically, both UC and CD involve the primary symptoms of abdominal pain and diarrhoea. These conditions are refractory and recurrent, causing high levels of patient suffering.
The aetiology and pathogenesis of IBD are not fully understood and, moreover, there is currently no specific treatment. The primary therapeutic approaches in clinical practice are derived from western medicine including traditional treatment with sulphasalazine (SASP; also known as 5-aminosalicyclic acid (5-ASA)) or the administration of steroids, immunosuppressive agents, or new biological agents. However, long-term treatment with steroids and immunosuppressants can cause serious adverse reactions, whereas new types of biological agents not only are expensive and economically burdensome to patients but also have unsatisfactory long-term efficacy.
Since the 1990s, there have been an increasing number of clinical studies of acupuncture and moxibustion treatment for IBD, and the existing investigations have demonstrated that acupuncture and moxibustion can effectively control bowel inflammation by providing multitargeted regulation of the body’s physiological balance [
Foreign-language and Chinese databases were searched. The Medline, Embase, and Cochrane Library databases were searched for English-language reports regarding RCTs. The Medline database was searched from 1966 to December 31, 2012, and Embase from 1974 to December 31, 2012. The Chinese literature databases that were searched include the China National Knowledge Infrastructure Database (CNKI), the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), and the Chinese Biomedical Literature Database (CBM). The CNKI and CBM were searched to retrieve relevant studies from January 1, 1949, to December 31, 2012, whereas the VIP was searched to retrieve relevant studies from January 1, 1989, to December 31, 2012. The keywords used to for the Chinese-language literature include “inflammatory bowel diseases,” “ulcerative colitis”, “Crohn’s disease”, “acupuncture”, “moxibustion”, “acupoint”, and “acupuncture treatment”; the keywords used for English-language literature included “acupuncture”, “moxibustion”, “inflammatory bowel diseases,” “ulcerative colitis”, and “Crohn’s disease” Based on the specific circumstances of the different databases, comprehensive searches for combinations of keywords and for wildcards were conducted to ensure the completeness of the search results.
(1) Research subjects: included studies were required to have enrolled patients with an unequivocal diagnosis of IBD (including UC and CD); no restrictions on race, age, or sex were imposed. (2) Study design: included studies were required to be RCTs in Chinese or English that evaluated the efficacy of acupuncture and/or moxibustion treatment for IBD. (3) Experimental group interventions: included studies were required to feature an experimental group that mainly received acupuncture and/or moxibustion treatment (including filiform needles, electroacupuncture, moxibustion, or cupping, among other techniques), either alone or in conjunction with other therapies (such as drug therapy), without differentiating among different acupuncture and moxibustion techniques, the selection of acupoints, or needle material. For studies in which the treatment group received acupuncture and/or moxibustion treatment combined with medication, the same drug had to be administered to both the treatment group and the control group. (4) Control group interventions: included studies were required to feature a control group that received medication, placebo, or sham acupuncture controlled treatment(s). (5) Outcome measurements: the outcome measurements of included studies had to include overall clinical efficacy, general conditions, changes in symptoms, serum inflammatory markers, and/or colonoscopic findings. (6) Availability: the full text or sufficiently informative abstracts of included studies had to be accessible.
The following types of studies were excluded from this analysis: (1) RCTs that lacked clear diagnostic criteria or basic information of the subjects or interventions; (2) serial observations, case reports, expert experiences, or descriptive analyses without control groups; (3) studies that compared different acupuncture and moxibustion techniques or selection of different acupoints to control groups; (4) studies that compared acupoint injections to drug therapy; (6) studies that were duplicate for retrieving or publishing.
The methodological quality of the included trials was evaluated using a modified Jadad quality scale (Table
Modified Jadad quality scale.
Aspects | Details | Score |
---|---|---|
Randomization | Appropriate if random sequence is generated by computer or similar methods | 2 |
Unclear if a trial does not describe its method of randomization | 1 | |
Inappropriate if a study uses an alternate assignment method, such as the allocation of odd and even numbers | 0 | |
| ||
Randomization concealment | Appropriate if either the distribution scheme is controlled by a center or pharmacy, containers with consistent serial numbers being used, on-site computer control, sealed opaque envelopes, or any other allocation method that clinicians and subjects are unable to predict | 2 |
Unclear if only a random number table or other random allocation scheme is employed | 1 | |
Inappropriate if either of alternate allocation, case numbers, days of the week, an open-label random number table, serial coded envelopes, or any other method with predictable assignments is used | 0 | |
Absent if randomization is not used | 0 | |
| ||
Blinding method | Appropriate if a completely identical placebo form or a similar method is used | 2 |
Unclear if the trial was described as blinded, but no methodological information regarding the blinding was provided | 1 | |
Inappropriate if the double-blind method is not adopted or if the blinding method is improper, such as a comparison between tablets and injections | 0 | |
| ||
Withdrawal and exit | The number and reasons of patients who withdraw or exit are described | 1 |
The number and reasons of patients who withdraw or exit are not described | 0 |
In accordance with the predetermined inclusion criteria, two researchers independently performed a rigorous screening to identify qualified trials, and they extracted data from these trials using a predesigned data extraction form independently. The extracted data included methodological features of the studies, demographic characteristics, treatment and control measurements, and primary outcome indicators. A third evaluator verified the consistency of the data, and any inconsistencies were addressed through discussion.
The RevMan software package from the Cochrane Collaboration (Oxford, UK), version 5.1, was used for meta-analysis of the data. In the analysis of clinical efficacy, count data were assessed in terms of risk ratios (RRs), and continuous variables were assessed in terms of mean difference (MD). Both count data and continuous variables are expressed as efficacy values with 95% confidence intervals (CIs). If the meta-analysis results exhibited heterogeneity (defined as results of tests of heterogeneity that indicated that
Using the search and retrieval strategy, a total of 746 studies were initially retrieved from the six aforementioned medical databases, including 152 English studies and 594 Chinese studies. The bibliographic information for these studies was imported into Microsoft Excel, and 348 duplicated titles were deleted. The titles and abstracts of the remaining studies were read to exclude irrelevant studies; after this process, 195 studies remained. These 195 studies were downloaded and full texts were read; using the pre-determined exclusion criteria, 152 irrelevant studies were excluded. Finally, 43 studies were selected for inclusion [
Flowchart of trial selection process. CNKI: China National Knowledge Infrastructure Database; VIP: Chongqing VIP Chinese Science and Technology Periodical Database; CBM: Chinese Biomedical Literature Database; RCT: randomized controlled trial.
Among the 43 included studies, there was one CD study [
Acupuncture and moxibustion therapy was the main intervention in the treatment groups of the examined RCTs. These treatments primarily involved acupuncture and/or moxibustion, although certain studies examined acupoint catgut embedding therapy, acupoint application, and auricular acupressure. In particular, among the 43 included studies, acupuncture and moxibustion therapy was used as the intervention method for the treatment group in 17 studies [
The main outcome indicators reported in the included studies were overall efficacy, colonic activity indices, clinical symptom scores, fibre colonoscopy results, laboratory test findings (including evaluations of T lymphocyte subpopulations and immunoglobulin), and adverse reactions to treatments. The general data and methodological quality of the included studies are presented in Table
Characteristics and methodological quality of included studies.
Study | Sample size ( |
Sex (male/female) | Age (mean or range) | Type of IBD | Followup | Methodology quality score |
---|---|---|---|---|---|---|
Ma and Zhang, 1997 [ |
90 (60/30) | 56/34 |
|
UC | No | 1 |
Gao, 1997 [ |
66 (46/20) | 27/39 |
|
UC | No | 1 |
Wu et al., 1999 [ |
151 (65/56/30) | ND |
|
UC | No | 1 |
Li et al., 2008 [ |
67 (34/33) | 42/25 | 35.5 | UC | No | 1 |
Mo et al., 2010 [ |
62 (31/31) | 35/27 | 35.5 | UC | No | 1 |
X. Guo and F. Guo, 2010 [ |
55 (28/27) | 38/17 | 38.77 | UC | No | 1 |
Yang et al., 2011 [ |
100 (50/50) | 61/39 |
|
UC | No | 1 |
Zhou and Jin, 2008 [ |
220 (110/110) | 131/89 |
|
UC | Yes | 4 |
Han et al., 2012 [ |
81 (41/40) | 47/34 |
|
UC | No | 1 |
Jiang, 2012 [ |
80 (40/40) | 39/41 |
|
UC | No | 3 |
Zhou, 2003 [ |
66 (34/32) | 31/35 | 40.8 | UC | No | 1 |
Din et al., 2009 [ |
61 (30/31) | 32/29 |
|
UC | No | 1 |
Wu et al., 2000 [ |
46 (30/16) | 25/21 |
|
UC | No | 1 |
Wen, 2003 [ |
69 (39/30) | 35/34 |
|
UC | No | 1 |
Wang et al., 2006 [ |
60 (30/30) | 28/32 | 38.5 | UC | No | 1 |
Xu et al., 2010 [ |
60 (28/32) | 35/25 |
|
UC | No | 2 |
Zhang, 2012 [ |
60 (30/30) | 32/28 |
|
UC | No | 1 |
Chi and Yu, 2011 [ |
84 (44/40) | 36/48 |
|
UC | No | 1 |
Luo, 2009 [ |
76 (40/36) | 42/34 |
|
UC | No | 1 |
Li et al., 2006 [ |
68 (40/28) | 40/28 |
|
UC | Yes | 1 |
Tian et al., 2012 [ |
106 (53/53) | 46/60 |
|
UC | No | 1 |
Chen, 2004 [ |
130 (100/30) | 80/50 |
|
UC | No | 1 |
Li et al., 2006 [ |
116 (56/60) | 52/64 |
|
UC | No | 2 |
Duan et al., 2012 [ |
640 (320/320) | 406/234 |
|
UC | No | 1 |
Sun and Wang, 1998 [ |
88 (45/43) | 43/45 |
|
UC | No | 1 |
Wang, 2008 [ |
108 (54/54) | 78/30 |
|
UC | No | 1 |
Ma and Xu, 2005 [ |
92 (47/45) | 51/41 |
|
UC | No | 2 |
Cui, 2010 [ |
48 (24/24) | 27/21 |
|
UC | No | 2 |
Guo et al., 2007 [ |
33 (22/11) | ND | ND | UC | No | 1 |
Wang et al., 2009 [ |
78 (39/39) | 44/34 |
|
UC | No | 1 |
Long and Yang, 2010 [ |
46 (23/23) | 20/26 |
|
UC | No | 1 |
Chen, 2010 [ |
168 (84/84) | 91/77 | 38.4 | UC | No | 1 |
Sun and Wang, 2001 [ |
55 (35/20) | 32/23 |
|
UC | No | 1 |
Wang et al., 2006 [ |
45 (27/18) | 23/22 | 40.5 | UC | No | 1 |
Shi et al., 2006 [ |
60 (30/30) | 34/26 |
|
UC | No | 2 |
Qun et al., 2012 [ |
63 (33/30) | 32/31 |
|
UC | No | 1 |
Xu, 2006 [ |
110 (56/54) | 59/51 |
|
UC | No | 1 |
Zhang et al., 2011 [ |
60 (30/30) | 38/22 |
|
UC | No | 2 |
Joos et al., 2006 [ |
29 (15/14) | 10/19 |
|
UC | Yes | 7 |
Yang and Yan, 1999 [ |
62 (32/30) | 30/32 |
|
UC | No | 1 |
Joos et al., 2004 [ |
51 (27/24) | 15/36 | ND | CD | Yes | 5 |
Ma, 1999 [ |
90 (60/30) | 56/34 |
|
UC | No | 1 |
Ma, 2005 [ |
121 (76/45) | 67/54 |
|
UC | No | 1 |
Interventions and outcomes of included studies.
Study | Intervention | Control | Outcome measurement |
---|---|---|---|
Ma and Zhang, 1997 [ |
Acupuncture + sparrow-pecking moxibustion | SASP + metronidazole | Efficacy |
Gao, 1997 [ |
Acupoint application + moxibustion + decoction of traditional Chinese medicine | Traditional Chinese medicine | Efficacy |
Wu et al., 1999 [ |
Drug-separated moxibustion | SASP | Efficacy, T lymphocyte subpopulations, HLA-DR antigen |
Li et al., 2008 [ |
Moxa-box moxibustion + SASP | SASP | Efficacy, haemorheology, immunoglobulin, T lymphocyte subpopulations |
Mo et al., 2010 [ |
Moxa-box moxibustion + traditional Chinese medicine enema | Traditional Chinese medicine enema | Efficacy |
X. Guo and F. Guo, 2010 [ |
Warm moxibustion of acupoints | SASP + PAT | Efficacy, T lymphocyte subpopulations |
Yang et al., 2011 [ |
Ginger moxibustion | Diphenoxylate | Efficacy |
Zhou and Jin, 2008 [ |
Electroacupuncture + ginger moxibustion + SASP | SASP | Medical condition, efficacy, intestinal mucosa pathology, adverse reactions |
Han et al., 2012 [ |
Auricular acupressure + salicylic acid preparations + traditional Chinese medicine + traditional Chinese medicine enema | Salicylic acid preparations + traditional Chinese medicine + traditional Chinese medicine enema | Enema retention time, efficacy |
Jiang, 2012 [ |
Abdominal acupuncture + acupoint catgut embedding | Bupi Yichang pills | Symptom scores, efficacy, fibre colonoscopy |
Zhou, 2003 [ |
Ginger moxibustion | SASP + prednisone tablets | Efficacy |
Din et al., 2009 [ |
Ginger moxibustion | SASP | Efficacy |
Wu et al., 2000 [ |
Moxibustion with herbal medicine underneath | SASP | Efficacy, colonic mucosal histopathology, mucin |
Wen, 2003 [ |
Drug-separated moxibustion | SASP | Efficacy, immunoglobulin |
Wang et al., 2006 [ |
Drug-separated moxibustion | SASP + metronidazole tablets | Efficacy, immunoglobulin, T lymphocyte subpopulations, NK content |
Xu et al., 2010 [ |
Herb-partitioned moxibustion | SASP | Efficacy, adverse reactions |
Zhang, 2012 [ |
Drug-separated moxibustion | SASP | Efficacy |
Chi and Yu, 2011 [ |
Umbilical compression with traditional Chinese medicine + SASP | SASP | Efficacy |
Luo, 2009 [ |
Balance cupping | Enteritidis tablet | Efficacy, symptom scores, immunoglobulin |
Li et al., 2006 [ |
Application of musky warm umbilical cream + use of a specific electromagnetic spectrum therapeutic apparatus | SASP | Efficacy |
Tian et al., 2012 [ |
Acupoint application | SASP | Efficacy, symptom scores |
Chen, 2004 [ |
Acupoint catgut embedding | SASP | Efficacy |
Li et al., 2006 [ |
Acupoint catgut embedding | SASP | Efficacy, stool characteristics, abdominal pain |
Duan et al., 2012 [ |
Acupoint catgut embedding + traditional Chinese medicine enema | Traditional Chinese medicine enema | Efficacy, routine stool tests |
Sun and Wang, 1998 [ |
Warm acupuncture + traditional Chinese medicine enema | Traditional Chinese medicine enema | Efficacy |
Wang, 2008 [ |
Warm acupuncture | SASP + western medicine enema | Efficacy |
Ma and Xu, 2005 [ |
Acupuncture + TDP | SASP | Efficacy |
Cui, 2010 [ |
Acupuncture + moxibustion + SASP | SASP | Efficacy, serum levels of TNF- |
Guo et al., 2007 [ |
Acupuncture + traditional Chinese medicine enema | Traditional Chinese medicine enema | Efficacy, intestinal microscopy |
Wang et al., 2009 [ |
Electroacupuncture + ginger moxibustion + traditional Chinese and western medicine enema | Traditional Chinese and western medicine enema | Efficacy |
Long and Yang, 2010 [ |
Acupuncture + traditional Chinese medicine enema | Traditional Chinese medicine enema | Efficacy, colonoscopy |
Chen, 2010 [ |
Acupuncture + ginger moxibustion + traditional Chinese medicine enema | Traditional Chinese medicine enema | Efficacy |
Sun and Wang, 2001 [ |
Acupuncture + ginger moxibustion | Shuanghuanglian compound + norfloxacin + gentamicin | Efficacy |
Wang et al., 2006 [ |
Warm acupuncture | SASP | Efficacy |
Shi et al., 2006 [ |
Electroacupuncture + moxibustion | SASP | Efficacy, serum levels of TNF- |
Qun et al., 2012 [ |
Acupuncture + moxibustion + TDP | SASP | Efficacy, intestinal mucosa pathology, immunoglobulin |
Xu, 2006 [ |
Ginger moxibustion + SASP | SASP | Efficacy |
Zhang et al., 2011 [ |
Traditional acupuncture + Chinese medicine decoction | SASP | Efficacy, symptom scores, serum levels of IL-8 and IL-10 |
Joos et al., 2006 [ |
Traditional acupuncture + moxibustion | Sham acupuncture | CAI, QLO, general well-being, C-reactive protein, serum |
Yang and Yan, 1999 [ |
Acupuncture + moxibustion | SASP | Efficacy, routine examination of faeces, electrogastrograms, sigmoidoscopy |
Joos et al., 2004 [ |
Traditional acupuncture + moxibustion | Sham acupuncture | CDAI, QLO, general condition, C-reactive protein, serum |
Ma, 1999 [ |
Acupuncture + sparrow-pecking moxibustion | SASP | Efficacy |
Ma, 2005 [ |
Acupuncture | SASP | Efficacy |
SASP: sulphasalazine; IBDQ: Inflammatory Bowel Disease Questionnaire; CAI: Colitis Activity Index; QOL: quality of life; CDAI: Crohn's Disease Activity Index; PAT: pipemidic acid tablet; sham acupuncture: superficial needling at nonacupoints.
The assessments for bias risk revealed that among the 43 RCTs included in this systematic evaluation, nine RCTs reported their random allocation methods [
Three of the 43 included trials were of high quality [
The 43 included RCTs featured complex interventions and different reported outcomes, with no unified efficacy standard. To develop a general understanding of the therapeutic effect of acupuncture and moxibustion therapy for IBD, intervention measurements and therapies for control group were further refined. We limited the treatment group methods to acupuncture or moxibustion alone, or a combination of acupuncture and moxibustion; this limitation produced 10 studies that compared one of the these treatments with oral SASP for the treatment of UC [
The results of heterogeneity tests indicated that
Forest plot of acupuncture and/or moxibustion for ulcerative colitis Compared to SASP.
RevMan, version 5.1, was used to conduct a funnel plot analysis of the aforementioned 10 studies, and the resulting graph was symmetrical, suggesting that these studies demonstrated no obvious publication bias (Figure
Funnel plot of randomized controlled trials using acupuncture and/or moxibustion for ulcerative colitis.
Based on the RCTs examined in this study, the methodological quality of the clinical trials regarding the examined topic was generally low, and few studies provided robust evidence. Randomization and allocation concealment are among the ways in which bias can arise, and the vast majority of the examined trials only mentioned “randomization”, without describing the specific methods used or whether allocation concealment was implemented. Thus, nonstandard “randomization” was widespread. The selective reporting of research results or the loss of trial data can also lead to reporting bias. Among the 43 included trials, only two studies reported the numbers of withdrawals from the study and the reasons; because none of the other trials reported exit data or cases lost to followup, the efficacy conclusions of these trials might be exaggerated. Most of the studies did not utilize blinding, producing a high probability of bias. The overall quality of the studies was low, affecting the strength of the evidence that was examined in this systematic evaluation.
Adequate attention must be devoted to the important factor of sample size in RCTs that address the examined topic. At present, only two relevant RCTs have featured sample sizes of more than 200 individuals. Insufficient sample sizes can reduce the power of a test, resulting in limited reliability of the results and conclusions, that do not truly reflect the overall effects observed in a study. Low statistical power will reduce the magnitude of evidence that RCTs can provide.
In this study, the specific interventions described in the included studies, which included acupuncture, herb-partitioned moxibustion, ginger-partitioned moxibustion, moxibustion, electroacupuncture, abdominal acupuncture, acupuncture catgut embedding, acupoint application, cupping, and auricular pressure, were treated as one type of therapy, without considering the differences in acupoint selection or therapeutic techniques. Therefore, the results of this study might indicate overall efficacy trends, but they cannot be utilised to draw definitive conclusions, thus limiting the extent to which the conclusions of this investigation can be applied.
The majority of the included studies selected clinical efficacy as the outcome measurement. Thus, there may exist subjectivity in the evaluations of the results. With little use of objective indicators, such as clinical symptom scores, endoscopic scores, or pathologic scores, the tendency towards subjective judgements weakened the credibility of conclusions regarding the effectiveness of acupuncture and moxibustion. With regard to long-term efficacy, most of the included studies did not conduct long-term followup, or if someone did, either the data for withdraw or the follow-up methods were not described. As a result, the long-term efficacy of acupuncture and moxibustion treatment for IBD cannot be determined.
The objectivity and accuracy of systematic evaluations rely on high-quality RCTs. The findings of this systematic evaluation are somewhat limited due to the generally low quality of the existing studies. Thus, it is recommended that future research should be based on the Consolidated Standards of Reporting Trials (CONSORT) statement [
The results of this study suggest that acupuncture and moxibustion treatment demonstrated better overall efficacy than oral SASP in treating IBD. However, given the limitations of this systematic evaluation and the included studies, definitive conclusions cannot be drawn with regard to the specific efficacy of acupuncture and moxibustion treatment for IBD. Currently published RCTs have not provided sufficient evidence for the effectiveness of acupuncture and moxibustion for IBD; thus, multicentre, double-blind RCTs with large sample sizes are still required to provide higher levels of evidence.
The authors of this paper state that they have no conflict of interests associated with this investigation.
Jun Ji, Yuan Lu, and Huirong Liu contributed equally to this work.
This study was financially supported by grants from the 973 Program of China (no. 2009CB522900), National Natural Science Foundation of China (no. 81173331), and Shanghai Municipal Health Bureau (no. 20124028; no. 2010QL025B).