Efficacy of biologic therapy in patients with chronic pouchitis

Abstract

Dear Editor: Pouchitis is one of the most common and debilitating complications after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). One common theory of pathogenesis is bacterial overgrowth in the pouch due to faecal stasis. Antibiotics are the mainstay of therapy in a patient with a first episode of acute pouchitis, although optimal treatment regimens remain to be defined. In several patients, pouchitis becomes chronic and refractory to conventional therapies including antibiotics, corticosteroids, immunomodulators and probiotics. In our research, we measured mucosal cytokine levels in the pouch after IPAA for UC. At 6 and 12 months after ileostomy closure, the mucosal cytokine levels were significantly higher compared with those at ileostomy closure. Furthermore, the mucosal cytokine levels were higher in patients with pouchitis than in those without pouchitis. In other studies, we found that infliximab (IFX) suppresses endoscopic disease activity and the mucosal cytokine production in patients with inflammatory bowel diseases. Based on these observations, biologic agents including IFX may be effective for pouchitis in which mucosal cytokine production is elevated. Recently, biologic agents have been used as rescue therapy in the management of refractory pouchitis. In a Spanish multicentre study, 31 UC patients with chronic refractory pouchitis were treated with IFX. At week 8, 21 % patients achieved complete response and 63 % showed partial clinical response. At weeks 26 and 52, 33 and 27 % achieved complete response and 33 and 18 % showed partial clinical response, respectively. Similar results have been reported in other studies. The same Spanish group evaluated the efficacy of adalimumab (ADA) in patients with refractory pouchitis previously treated with IFX. Eight patients with chronic refractory pouchitis were treated with ADA. At week 8, 13 % of the patients achieved remission and 62 % showed a clinical response. At week 26, 13 % achieved remission and 38 % showed a clinical response. At week 52, 50 % of the patients avoided a permanent ileostomy. This study suggests that ADA treatment is an alternative for patients with chronic refractory pouchitis previously treated with IFX. Based on the data from the previous studies, biologic agents are effective in the short and mid terms in patients with chronic refractory pouchitis. However, the efficacy of biologic agents for refractory pouchitis should be further assessed. The previous studies are retrospective with the absence of a control group. Endoscopic findings were not available in all patients. Furthermore, the number of patients investigated was small. Randomized controlled trials with a large number of patients are needed in order to evaluate a definite efficacy of biologics in patients with refractory pouchitis. Endoscopic evaluation should be conducted before and after treatment. We hope that biologic therapy can avoid a permanent ileostomy in patients with severe intractable pouchitis after IPAA. It should be further assessed whether biologic agents can significantly reduce the necessity of permanent ileostomy in this group of patients.