Therapy for treatment and prevention of pouchitis

What is pouchitis?

Some people with ulcerative colitis have their colon and rectum removed with construction of a pouch (made from a loop of small intestine) in place of the rectum - known as ileal pouch-anal anastomosis (IPAA) surgery. Pouchitis is inflammation of the surgically-constructed pouch. Symptoms of active pouchitis include diarrhea, increased stool frequency, abdominal cramping, fecal urgency, tenesmus (feeling of constantly needing to pass stools), and incontinence. Acute refers to symptoms that last less than four weeks while chronic refers to symptoms that last more than four weeks. Periods when symptoms stop are called 'remission'.

What therapies are used for pouchitis?

Therapies used for pouchitis include antibiotics (drugs for bacteria infections), budesonide enemas (a steroid drug), probiotics (helpful bacteria), biologic agents that target tumor necrosis factor, glutamine suppositories (an amino acid), butyrate suppositories (short chain fatty acid), bismuth enemas (diarrhea medication), allopurinol (a purine analogue drug), and tinidazole (an anti-parasitic drug).

What did the researchers investigate?

The researchers investigated whether these medications produce remission in people with active pouchitis, maintain remission in people with inactive pouchitis or prevent pouchitis in people who've had IPAA surgery. Side effects were also assessed. The medical literature was searched up to 25 July 2018.

What did the researchers find?

We found 15 studies with a total of 547 participants. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis.

Acute pouchitis: It is uncertain whether ciprofloxacin is more effective than metronidazole for treatment of acute pouchitis (1 study, 16 participants). Side effects included vomiting, metallic taste and temporary damage to nerves. It is unclear whether there are any differences between metronidazole and budesonide enemas in terms of clinical remission, symptom improvement or side effects (1 study, 26 participants). Side effects included anorexia, nausea, headache, lack of energy and strength, metallic taste, vomiting, pins and needles, and depression. It is uncertain whether there are any differences between rifaximin and placebo in terms of clinical remission, symptom improvement, or side effects (1 study, 18 participants). Side effects included diarrhea, flatulence, nausea, rectal pain, vomiting, thirst, yeast infection, common cold, increased liver enzymes, and cluster headache. It is uncertain whether there is any difference between Lactobacillus GG and placebo in symptom improvement (1 study, 20 participants. The results of these studies are uncertain due to low event numbers caused by the small numbers of people who participated in the studies.

Chronic pouchitis: It is uncertain whether De Simone Formulation (a probiotic formulation) is more effective than placebo for maintaining remission in people with inactive disease (2 studies, 76 participants). Side effects included abdominal cramps, vomiting and diarrhea. It is unclear whether there is any difference in effectiveness between adalimumab and placebo for treating chronic pouchitis(1 study, 13 participants). It is unclear whether there is any difference between glutamine and butyrate suppositories for maintenance of remission (1 study, 19 participants). It is unclear whether there are any differences in symptom improvement or side effects between bismuth carbomer foam enemas and placebo (1 study, 40 participants). Side effects included diarrhea, worsening symptoms, cramping, sinus infection, and abdominal pain. The results of these studies are uncertain due to the small number of people who participated in the studies.

Prevention of pouchitis: It is uncertain whether De Simone Formulation is more effective than placebo for prevention of pouchitis (1 study, 40 participants). However, it is unclear whether there is any difference in prevention of pouchitis between De Simone Formulation and a no treatment control group (1 study, 28 participants). It is unclear whether there are any differences in prevention of pouchitis between Clostridium butyricum MIYAIRI and placebo (1 study, 17 participants), Bifidobacterium longum and placebo (1 study, 12 participants), allopurinol and placebo (1 study, 184 participants) and tinidazole and placebo (1 study, 38 participants). The results of these studies are uncertain due to the small number of people who participated in the studies.

The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. More research is needed to determine which of these different medications are best for treatment of pouchitis.

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.

Read the full 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 strategy: 

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 (a probiotic 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).

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