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Acupuncture is effective in inducing and maintaining remission of active Crohn's disease


Introduction


Crohn's disease (CD) is a chronic, recurrent inflammatory disease that can affect any part of the digestive tract. The main symptoms include abdominal pain, diarrhea, and weight loss. While the highest prevalence of CD is in North America and Europe (range: 319/105–322/105), a rapid increase in the incidence of CD occurs in newly industrialized countries such as China, owing to the impact of westernized diets and environmental changes on individual intestinal microbiota. The pathogenetic mechanism of CD involves dysfunctional intestinal microbiota, which may impair the integrity of the intestinal barrier through the activation of inflammatory pathways in genetically susceptible individuals.


The efficacy of currently available drugs for CD (such as aminosalicylic acid, glucocorticoids, immunomodulators, and biological agents) is rather unsatisfactory and some of these drugs are also costly and have several side effects. About 1/3–2/3 of patients fail to respond to TNF-α antagonists or have decreased response over time. Therefore, developing effective therapies for CD is imperative. Acupuncture is an alternative therapy that has been used for the treatment of inflammatory bowel diseases around the world. Acupuncture and moxibustion are often used together to achieve synergistic effect.


Research in context


Evidence before this study


Although four randomized controlled trials (three in English and one in Chinese) as well as two observational trials report acupuncture treatment for Crohn's disease (CD), the quality of this evidence is not optimal and needs to be improved. As described in a meta-analysis, there are very few robust clinical trials of acupuncture for CD. Further, conventional drugs and biologic are effective for only a fraction of patients, but no study has been made on testing the effect of acupuncture and moxibustion on CD patients who are unresponsive, intolerant or dependent on these medications.


Added value of this study

This is the first randomized, sham controlled, parallel-group, 48-week follow-up clinical trial that evaluated the efficacy and safety of acupuncture for mildly and moderately active patients with CD who had poor drug response. The study provides stronger evidence that 12 weeks of acupuncture was safe and effective in inducing and maintaining disease remission, and that this effect maintained for at least 48 weeks. Its therapeutic effects may be related to increased relative abundance of anti-inflammatory bacteria as well as short chain fatty acids-producing bacteria, increased intestinal epithelial barrier function, and inhibition of Th1/Th17-related pro-inflammatory cytokines.


Implications of all the available evidence

CD is poorly controlled by currently available medications and the effects are often short-lasting. The conclusions of this study will encourage the clinical use of acupuncture as a safe and effective alternative treatment for mild to moderately active CD patients, especially those who are poorly responsive or intolerant to medications. Future research may include refining and improving the effect of acupuncture by using differentiated acupuncture protocols based on patient disease subtypes such as disease location or disease behavior, and further exploring inflammatory mechanism.


Methods

This 48-week, randomized, sham controlled, parallel-group clinical trial was performed at a tertiary outpatient clinic in China. From April 2015 to November 2019, 66 patients (mean age 40·4, 62·1% were male, all were Han Chinese) with mild to moderate active CD and unresponsive to drug treatment were enrolled and randomly assigned equally to an acupuncture group or a sham group. The treatment group received 3 sessions of acupuncture plus moxibustion per week for 12 weeks and a follow-up of 36 weeks.


Intervention

Acupuncture group: We selected acupoints including Zhongwan (CV12) and bilateral Shangjuxu (ST37), Sanyinjiao (SP6), Gongsun (SP4), Taichong (LR3), Taixi (KI3), Hegu (LI4), and Quchi (LI11) according to the World Health Organization standard. Single-use 0·30 × 40 mm or 0·30 × 25 mm acupuncture needles (Hwato, Suzhou, China) were vertically inserted into each acupoint to 20–30 mm depth to obtain a deqi sensation (a soreness, distention, numbness or heaviness sensation). Bilateral Zusanli (ST36) and Tianshu (ST25) were selected for moxibustion. Pure moxa sticks (diameter: 2·8 cm; Hanyi, Nanyang, China) were ignited and fixed on a moxibustion stand at a distance of 3–5 cm to the surface of acupoints. The temperature of skin surface at the acupoints was maintained at 43 ± 1 °C and monitored with a miniature infrared thermometer (Fluke 62, Fluke Corporation, Everett, WA, USA). Acupuncture and moxibustion were concomitantly performed for 30 min。


Findings

At week 12, the clinical remission rate (the primary outcome) and clinical response rate of acupuncture group were significantly higher than that of sham group, with a difference of 42·4% (95% CI: 20·1%-64·0%) and 45·5% (95% CI: 24·0%-66·9%), respectively, both of which maintained at week 48. The acupuncture group had significantly lower CD activity index and C-reactive protein level at week 12, which maintained at 36-week follow-up. The CD endoscopic index of severity, histopathological score, and recurrence rate at week 48 were significantly lower in acupuncture group. The number of operational taxonomic unit of intestinal microbiota and relative abundance of Faecalibacterium prausnitzii and Roseburia faecis were increased. Plasma diamine oxidase, lipopolysaccharide, and Th1/Th17 related cytokines were decreased in 12-week after acupuncture.


Acupuncture treatment had a better effect on clinical remission and clinical response to CD, as well as on decreasing the CDAI score and CRP level at week 12 and 36-week follow-up .


Interpretation

Acupuncture was effective in inducing and maintaining remission in patients with active CD, which was associated with increased abundance of intestinal anti-inflammatory bacteria, enhanced intestinal barrier, and regulation of circulating Th1/Th17-related cytokines.


My comments:

The result is published in a Lancet Journal.


Reference:

Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: A randomized controlled trial. EClinicalMedicine. 2022 Feb 12;45:101300. doi: 10.1016/j.eclinm.2022.101300.

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