Treatment of Pouchitis
It has been observed that the usual anti-inflammatory therapies are not as effective for pouchitis as for other forms of inflammatory bowel disease, whereas antibiotics seem to be more effective and have therefore become the mainstay of treatment for pouchitis. Many patients with IPAA can experience rapid and significant clinical improvement following the commencement of antibiotic treatment for acute onset of symptoms, even before endoscopy has been performed. For a first attack of typical pouchitis a course of empiric antibiotic therapy without endoscopy and biopsy is reasonable, but if there is easy access to endoscopic evaluation and biopsy, it is still preferable to visualise and biopsy the pouch mucosa before starting therapy.
Recurrent episodes, with similar features to the initial presentation, may be treated in the same manner as initially and the likelihood of diagnosing them accurately without endoscopy is high.
Antibiotics
Metronidazole has been evaluated in several randomised controlled trials, and an overall response rate of 73% has been demonstrated compared with a 10% response rate in patients receiving placebo.
Ciprofloxacin at a dose of 1000 mg/day was compared with metronidazole 20 mg/kg per day, given for 2 weeks, and both agents significantly reduced the PDAI, with all subscores showing improvement. However, patients who were given ciprofloxacin had greater reductions in mean total PDAI than those in the metronidazole group.
These findings, together with the frequent intolerance and potential occurrence of peripheral neuropathy caused by metronidazole, have placed ciprofloxacin as a first-line treatment for pouchitis, notwithstanding the rare occurrence of tendon rupture reported in patients receiving ciprofloxacin.
Rifaximin has been used as an alternative treatment for active pouchitis and has also been studied for its ability to maintain remission. In one study rifaximin was shown to maintain remission up to 3 months in 65% of patients who had remission induced with other antibiotics given for 2 weeks.
Combination antibiotic therapy has also been studied and has been found to be effective for treating pouchitis. In one study of combination therapy with ciprofloxacin and tinidazole, the antibiotic therapy was shown to be superior, in terms of PDAI reduction, over the administration of oral, enema or suppository of mesalamine.
Response to antibiotics has been used to classify patients with pouchits. Patients are considered to be antibiotic responsive when they have an episode of pouchitis that responds to a 2-week course of antibiotics, and are considered to be antibiotic dependent when the disease requires long-term, continuous antibiotic therapy to maintain remission. Those with antibiotic-resistant pouchitis fail to respond to antibiotics and may require oral or topical 5-aminosalicylates, corticosteroid therapy, or oral immunomodulator therapy, as outlined below.
'Second-line' Approach and Treatment of Chronic Pouchitis
As 10–20% of patients with pouchitis may progress to chronic pouchitis, which may be antibiotic dependent or antibiotic resistant, other therapeutic options are necessary in order to prevent pouch failure and the need for pouch excision or diversion.
Mesalamine-Containing Preparations
Several uncontrolled reports have suggested that mesalamine, given either in an oral delayed release formulation or in an enema formulation, may be of benefit in treating pouchitis. Given the small size of these reports or series, further properly controlled studies are needed. In cuffitis, when the residual cuff of rectal mucosa is inflamed, mesalamine suppositories appear to relieve symptoms (as well as improving endoscopic and histological findings) of cuffitis.
Corticosteroids
There are anecdotal reports regarding the usage of budesonide enemas in the treatment of pouchitis. However, there are not sufficient high quality data to recommend corticosteroids as a standard therapy for pouchitis routinely. These agents are currently reserved as second-line therapy, when antibiotics fail.
Combination of Antibiotics
For patients who are antibiotic resistant, the following combinations have been tried in different studies:
Rifaximin 2 g/day plus ciprofloxacin 1 g/day, for 15 days, with 89% of the patients achieving either improvement or remission.
Metronidazole 1 g/day plus ciprofloxacin 1 g/day, for 28 days, with 82% of the patients achieving remission.
Ciprofloxacin 1 g/day plus tinidazole 15 mg/kg per day, for 4 weeks, with 88% of the patients achieving remission.
'Dependent' Patients
After achieving remission, many patients become dependent on either antibiotics or, in some cases, on budesonide enemas. This brings up the therapeutic concept of treatment dependence, which may be managed with treatment with either azathioprine or 6-mercaptopurine.
Biological Agents
Infliximab has been shown to be effective in a small group of patients with chronic active pouchitis who do not respond to either antibiotics or oral budesonide.
In a difficult-to-treat subset of patients with pelvic pouches and Crohn's-like complications (namely, pouch fistulae and small bowel stricturing disease, unrelated to surgery), Haveran et al have shown encouraging results with treating pouch fistulising disease with infliximab and stricturing disease or antibiotic-resistant pouchitis with only an immunomodulator (either azathioprine or 6-mercaptopurine).
Probiotics
Response to antibiotic therapy supports the hypothesis that bacterial flora are, in some way, contributing to mucosal inflammation. This may be related to the fact that the pouch flora are distinct from normal small intestinal flora, and that the functional nature of the pouch predisposes to altered motility and stasis with resulting bacterial overgrowth .However, the importance of bacterial flora has also led researchers to test probiotics as a 'forced' means of altering the pouch bacterial flora. Using VSL #3, a probiotic preparation containing eight different probiotic bacteria strains, has been shown to prevent initial episodes of pouchitis, with only 10% of the patients receiving VSL #3 experiencing pouchitis compared with 40% of patients in the placebo group. This treatment was also shown to be effective in maintaining remission that was achieved with antibiotic therapy, with 15% of patients in the probiotic group relapsing compared with 100% of patients relapsing in the placebo group, up to 9 months.
Other Treatments
Several other approaches have been tried, including butyrate suppositories (based on its nature as being a major colonic mucosal nutrient and contributing to its mucosal barrier) as well as bismuth carbomer enemas, but these have yielded insufficient evidence on which to base therapeutic decisions.
Removal of white blood cells from circulation by means of leucocytapheresis has been reported as a potential therapy for patients with active pouchitis. Eight patients were treated in an open-label treatment protocol, six of whom achieved remission with no adverse reactions observed.
All of the above-mentioned treatment modalities were tried in small series and, as a result, drawing conclusions about their potential efficacy is difficult. However, the therapeutic approach should initially involve antibiotics, and should this fail or should the patient become antibiotic dependent, other options may be tried with clearly defined treatment endpoints and careful evaluation of these endpoints in the individual patient.