Topical Agents for Idiopathic Distal Colitis and Proctitis
Topical Agents for Idiopathic Distal Colitis and Proctitis
Rectally administered topical agents have demonstrated efficacy in the maintenance of distal colitis (DC) and proctitis and as they are rarely associated with significant blood drug levels, side effects are infrequent. The topical 5-aminosalicylic acid (5-ASA) suppositories and enemas target different regions of the distal colon and are effective for proctitis and DC, respectively. They demonstrate clinical results that are better than oral 5-ASAs and are preferred to topical steroids with better clinical, endoscopic and histological outcomes, without the risk of adrenal suppression. Disease resistant to topical agents, however, can be extremely difficult to manage. The addition of oral 5ASAs, steroids, immunosuppressants and the anti-tumor necrosis factor-α agents may be effective, but can result in significant side effects and not all patients will respond to the therapies. It is for these patients that new and novel therapies are required. Novel topical agents have been proposed for the management of resistant DC. These agents included butyrate, cyclosporine, and nicotine enemas, as well as tacrolimus suppositories, and tacrolimus, ecabet sodium, arsenic, lidocaine, bismuth, rebamipide and thromboxane enemas. While some of these agents appear to demonstrate impressive outcomes, the majority have only been examined in small open-labeled studies. There is thus a desperate need for more randomized double-blinded placebo controlled studies to investigate the clinical utility of these topical therapies. This review summarizes the efficacy of the established topical therapies, and explores the available data on the new and novel topical agents for the management of DC and proctitis.
Ulcerative colitis (UC) is a chronic inflammatory condition characterized by a life-long course of clinical remissions and exacerbations. Distal ulcerative colitis (DC), which is also known as left-sided colitis or E2 under the Montreal classification, is disease confined to the colon distal to the splenic flexure. Proctitis, or E1 by the Montreal classification, is disease localized to the rectum. DC or proctitis occurs in over 50% of UC patients and although this results in distressing symptoms, including stool frequency, tenesmus, urgency and bleeding, it can often be managed within the community. Resistant DC and proctitis, however, can be extremely challenging to manage. When topical rectal 5-aminosalicylic acid (5ASA) and steroid medications fail, oral agents including the 5ASAs, azathioprine (AZA)/6-mercaptopurine (6MP) and steroids may be employed, but they do not always help. Infliximab, a medication that binds the proinflammatory cytokine tumor necrosis factor-α (TNF-α) can also be effective in these patients with a clinical response in 68% and remission in about a third. There are still, however, a significant proportion of UC patients who do not achieve clinical improvement, let alone remission, with these agents. It is for these patients that new and novel therapies require investigation. This review explores the topical therapies currently available for proctitis and DC as well as those novel topical therapies with potential benefit to the patient with resistant distal disease.
Abstract and Introduction
Abstract
Rectally administered topical agents have demonstrated efficacy in the maintenance of distal colitis (DC) and proctitis and as they are rarely associated with significant blood drug levels, side effects are infrequent. The topical 5-aminosalicylic acid (5-ASA) suppositories and enemas target different regions of the distal colon and are effective for proctitis and DC, respectively. They demonstrate clinical results that are better than oral 5-ASAs and are preferred to topical steroids with better clinical, endoscopic and histological outcomes, without the risk of adrenal suppression. Disease resistant to topical agents, however, can be extremely difficult to manage. The addition of oral 5ASAs, steroids, immunosuppressants and the anti-tumor necrosis factor-α agents may be effective, but can result in significant side effects and not all patients will respond to the therapies. It is for these patients that new and novel therapies are required. Novel topical agents have been proposed for the management of resistant DC. These agents included butyrate, cyclosporine, and nicotine enemas, as well as tacrolimus suppositories, and tacrolimus, ecabet sodium, arsenic, lidocaine, bismuth, rebamipide and thromboxane enemas. While some of these agents appear to demonstrate impressive outcomes, the majority have only been examined in small open-labeled studies. There is thus a desperate need for more randomized double-blinded placebo controlled studies to investigate the clinical utility of these topical therapies. This review summarizes the efficacy of the established topical therapies, and explores the available data on the new and novel topical agents for the management of DC and proctitis.
Introduction
Ulcerative colitis (UC) is a chronic inflammatory condition characterized by a life-long course of clinical remissions and exacerbations. Distal ulcerative colitis (DC), which is also known as left-sided colitis or E2 under the Montreal classification, is disease confined to the colon distal to the splenic flexure. Proctitis, or E1 by the Montreal classification, is disease localized to the rectum. DC or proctitis occurs in over 50% of UC patients and although this results in distressing symptoms, including stool frequency, tenesmus, urgency and bleeding, it can often be managed within the community. Resistant DC and proctitis, however, can be extremely challenging to manage. When topical rectal 5-aminosalicylic acid (5ASA) and steroid medications fail, oral agents including the 5ASAs, azathioprine (AZA)/6-mercaptopurine (6MP) and steroids may be employed, but they do not always help. Infliximab, a medication that binds the proinflammatory cytokine tumor necrosis factor-α (TNF-α) can also be effective in these patients with a clinical response in 68% and remission in about a third. There are still, however, a significant proportion of UC patients who do not achieve clinical improvement, let alone remission, with these agents. It is for these patients that new and novel therapies require investigation. This review explores the topical therapies currently available for proctitis and DC as well as those novel topical therapies with potential benefit to the patient with resistant distal disease.
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