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. 2019 May 28;5(5):CD001176.
doi: 10.1002/14651858.CD001176.pub4.

Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis

Nghia Nguyen  1 , Bing Zhang, Stefan D Holubar, Darrell S Pardi, Siddharth Singh
Affiliations

Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis

Nghia Nguyen et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC).

Objectives: The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis.

Search methods: We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings.

Selection criteria: Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion.

Data collection and analysis: Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome.

Main results: Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear.Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty-three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty-seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty-five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty-eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy-five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence).Chronic pouchitis: Eighty-five per cent (34/40) of De Simone Formulation participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty-five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty-five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain.

Prevention: At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty-six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty-six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty-one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence).

Authors' conclusions: The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.

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Conflict of interest statement

Nghia Nguyen: None known

Bing Zhang: None known

Stefan D Holubar: None known

Darrell S Pardi: has received consulting fees from Assembly Bioscience, C3 Jian, Ferring, Janssen, Nestle, Merck, Otsuka, Salix, Seres, Gilead; research grants from Atlantic, Finch, Janssen, Merck, Pfizer, Salix, Seres, Takeda, Vedanta

Siddharth Singh ‐ has received consulting fees from AbbVie, Takeda, AMAG Pharmaceuticals; research grants from Pfizer and AbbVie; and honorarium for grant review from Pfizer.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Analysis 1.1
Analysis 1.1
Comparison 1 Ciprofloxacin versus metronidazole, Outcome 1 Clinical remission at 2 weeks.
Analysis 1.2
Analysis 1.2
Comparison 1 Ciprofloxacin versus metronidazole, Outcome 2 Adverse events.
Analysis 2.1
Analysis 2.1
Comparison 2 Metronidazole versus budesonide enema, Outcome 1 Clinical remission at 6 weeks.
Analysis 2.2
Analysis 2.2
Comparison 2 Metronidazole versus budesonide enema, Outcome 2 Clinical improvement at 6 weeks.
Analysis 2.3
Analysis 2.3
Comparison 2 Metronidazole versus budesonide enema, Outcome 3 Adverse events.
Analysis 3.1
Analysis 3.1
Comparison 3 Rifaximin versus placebo, Outcome 1 Clinical remission at 4 weeks.
Analysis 3.2
Analysis 3.2
Comparison 3 Rifaximin versus placebo, Outcome 2 Clinical improvement at 4 weeks.
Analysis 3.3
Analysis 3.3
Comparison 3 Rifaximin versus placebo, Outcome 3 Adverse events.
Analysis 4.1
Analysis 4.1
Comparison 4 Lactobacillus GG versus placebo, Outcome 1 Clinical improvement at 12 weeks.
Analysis 5.1
Analysis 5.1
Comparison 5 Glutamine versus butyrate, Outcome 1 Maintenance of clinical remission at 3 weeks.
Analysis 6.1
Analysis 6.1
Comparison 6 Bismuth enema versus placebo, Outcome 1 Clinical improvement at 3 weeks.
Analysis 6.2
Analysis 6.2
Comparison 6 Bismuth enema versus placebo, Outcome 2 Adverse events.
Analysis 7.1
Analysis 7.1
Comparison 7 De Simone Formulation versus placebo, Outcome 1 Maintenance of clinical remission at 9 to 12 months.
Analysis 7.2
Analysis 7.2
Comparison 7 De Simone Formulation versus placebo, Outcome 2 Adverse events.
Analysis 7.3
Analysis 7.3
Comparison 7 De Simone Formulation versus placebo, Outcome 3 No episodes of acute pouchitis.
Analysis 8.1
Analysis 8.1
Comparison 8 De Simone Formulation versus no treatment, Outcome 1 No episodes of acute pouchitis at 12 months.
Analysis 9.1
Analysis 9.1
Comparison 9 Bifidobacterium longum versus placebo, Outcome 1 No episodes of acute pouchitis at 6 months.
Analysis 10.1
Analysis 10.1
Comparison 10 Allopurinol versus placebo, Outcome 1 No episodes of acute pouchitis at 24 months.
Analysis 11.1
Analysis 11.1
Comparison 11 Tinidazole versus placebo, Outcome 1 No episodes of acute pouchitis at 12 months.
Analysis 12.1
Analysis 12.1
Comparison 12 Adalimumab versus placebo, Outcome 1 Clinical improvement at 4 weeks.
Analysis 13.1
Analysis 13.1
Comparison 13 Clostridium probiotic versus placebo, Outcome 1 No episodes of acute pouchitis at 24 months.
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References to other published versions of this review

    1. Holubar SD, Cima RR, Sandborn WJ, Pardi DS. Treatment and prevention of pouchitis after ileal pouch‐anal anastomosis for chronic ulcerative colitis. Cochrane Database of Systematic Reviews 2010, Issue 6. [DOI: 10.1002/14651858.CD001176.pub2] - DOI - PubMed
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