Ulcerative Colitis: Misunderstandings in Management
Ulcerative Colitis: Misunderstandings in Management
Past and ongoing therapeutic concepts for ulcerative colitis have only been moderately successful. A significant proportion of patients with ulcerative colitis will still have to undergo colectomy and overall half of the patients do not achieve sustained remission, leading to impairment of physical and mental health, social life, employment issues and sexual activity. Reluctance to treat patients early on with sufficiently potent drug regimens is obvious. Several popular misconceptions might have led to this situation. First, ulcerative colitis is still considered a more 'benign' disease than Crohn's disease. Furthermore, the general assumption is often that colectomy can 'cure' the disease. Mucosal healing as a therapeutic target has not been widely accepted. Finally, the use of antitumour necrosis factor antibodies in ulcerative colitis has been low because this treatment is considered to be less effective than in Crohn's disease. In the current review we try to disprove these misunderstandings by discussing relevant studies showing how harmful this disease can be and explaining why future studies targeting sustained suppression of inflammation could have an enormous impact on the natural course of the disease. Until these studies are available, we encourage physicians to intensify and maintain treatment until sustained remission and mucosal healing has been reached.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease of uncertain aetiology, with an incidence of 0.5–24.5 per 100 000 individuals per year and the highest estimates observed in the age group 20–35. The site of inflammation is the mucosal layer of the colon, but occasionally deeper layers can become inflamed. The disease almost always involves the rectum and from there continuously more proximal parts of the large bowel. At diagnosis, one-third of all patients with UC have distal colitis or proctosigmoiditis, one-third have left-sided colitis and one-third more proximal or pan-colitis. Between 15% and 30% of all patients with left-sided disease suffer from extension to more proximal colonic segments. The prevailing symptoms depend on the anatomic extent and the severity of inflammation. Most patients experience recurrent episodes of rectal bleeding, passage of mucus, increased stool frequency, abdominal cramps and pain. More severe cases may develop fever, anaemia and weight loss. The combination of symptoms, endoscopic appearance and radiography determine the severity of the disease. In many patients longstanding chronic inflammation leads to structural damage of the large bowel with impaired function and an enhanced risk of colorectal cancer. Aminosalicylates, corticosteroids, purine analogues and infliximab are the cornerstones of medical treatment for UC. The efficacy of adalimumab is currently under investigation. Between 5% and 50% of patients undergo colectomy during the course of the disease, mostly with an ileal pouch–anal anastomosis (IPAA). The wide variation in surgical rates can be explained by the availability of biological treatments, local and national guidelines and cultural differences.
The management of UC is undergoing significant changes. One aspect that has received more attention lately is the importance of mucosal healing. Already in 1923, however, Sir Arthur F Hurst, one of the first authors to describe UC, concluded in an article that 'no case of UC can be regarded as cured until the sigmoidoscope shows that the mucous membrane is perfectly healthy'. This treatment goal got lost or seems to have been ignored in the meantime by several generations of physicians. A century later, the role of mucosal integrity has again moved into the centre of interest.
Another paradigm shift has brought more attention to maintenance treatment. While it was generally accepted for decades that patients with UC only need treatment when symptoms occur, the idea of continued treatment that minimises or eliminates inflammation and reduces the risk of relapse now finds increasing support. The idea that the destructive effect of chronic inflammation in the gut is ongoing, even if patients do not have major symptoms is, however, well founded.
National guidelines that have been developed in Europe and elsewhere have mainly focused on when and how to use steroids, aminosalicylates and surgery. Only late in the course of the disease, immunosuppressants and tumour necrosis factor (TNF) blockers have been introduced rather hesitantly, even long after their advent on the market. The main concerns relate to the potential toxicity of the newer agents without paying attention to the harm caused by prolonged corticosteroid use or undertreatment. In a number of European countries there is the assumption among gastroenterologists and surgeons that TNF blockers should be offered only as an alternative to colectomy.
As the medical professionals taking care of patients with UC, we have to admit that our treatment concepts have not been very successful. Ongoing disease activity is present in ~50% of all patients with UC, colectomy rates remain high, and absence from social activities, unemployment, impaired quality of life, sick leave and disability pensions are higher in patients with UC than in the general population.
Could it be that misunderstandings and misconceptions have led to this rather unsuccessful outcome? The current paper is an attempt to list and critically review our potential misunderstandings and strategic views and to offer guidelines for more optimal care in the future.
Abstract and Introduction
Abstract
Past and ongoing therapeutic concepts for ulcerative colitis have only been moderately successful. A significant proportion of patients with ulcerative colitis will still have to undergo colectomy and overall half of the patients do not achieve sustained remission, leading to impairment of physical and mental health, social life, employment issues and sexual activity. Reluctance to treat patients early on with sufficiently potent drug regimens is obvious. Several popular misconceptions might have led to this situation. First, ulcerative colitis is still considered a more 'benign' disease than Crohn's disease. Furthermore, the general assumption is often that colectomy can 'cure' the disease. Mucosal healing as a therapeutic target has not been widely accepted. Finally, the use of antitumour necrosis factor antibodies in ulcerative colitis has been low because this treatment is considered to be less effective than in Crohn's disease. In the current review we try to disprove these misunderstandings by discussing relevant studies showing how harmful this disease can be and explaining why future studies targeting sustained suppression of inflammation could have an enormous impact on the natural course of the disease. Until these studies are available, we encourage physicians to intensify and maintain treatment until sustained remission and mucosal healing has been reached.
Introduction
Ulcerative colitis (UC) is a chronic inflammatory bowel disease of uncertain aetiology, with an incidence of 0.5–24.5 per 100 000 individuals per year and the highest estimates observed in the age group 20–35. The site of inflammation is the mucosal layer of the colon, but occasionally deeper layers can become inflamed. The disease almost always involves the rectum and from there continuously more proximal parts of the large bowel. At diagnosis, one-third of all patients with UC have distal colitis or proctosigmoiditis, one-third have left-sided colitis and one-third more proximal or pan-colitis. Between 15% and 30% of all patients with left-sided disease suffer from extension to more proximal colonic segments. The prevailing symptoms depend on the anatomic extent and the severity of inflammation. Most patients experience recurrent episodes of rectal bleeding, passage of mucus, increased stool frequency, abdominal cramps and pain. More severe cases may develop fever, anaemia and weight loss. The combination of symptoms, endoscopic appearance and radiography determine the severity of the disease. In many patients longstanding chronic inflammation leads to structural damage of the large bowel with impaired function and an enhanced risk of colorectal cancer. Aminosalicylates, corticosteroids, purine analogues and infliximab are the cornerstones of medical treatment for UC. The efficacy of adalimumab is currently under investigation. Between 5% and 50% of patients undergo colectomy during the course of the disease, mostly with an ileal pouch–anal anastomosis (IPAA). The wide variation in surgical rates can be explained by the availability of biological treatments, local and national guidelines and cultural differences.
The management of UC is undergoing significant changes. One aspect that has received more attention lately is the importance of mucosal healing. Already in 1923, however, Sir Arthur F Hurst, one of the first authors to describe UC, concluded in an article that 'no case of UC can be regarded as cured until the sigmoidoscope shows that the mucous membrane is perfectly healthy'. This treatment goal got lost or seems to have been ignored in the meantime by several generations of physicians. A century later, the role of mucosal integrity has again moved into the centre of interest.
Another paradigm shift has brought more attention to maintenance treatment. While it was generally accepted for decades that patients with UC only need treatment when symptoms occur, the idea of continued treatment that minimises or eliminates inflammation and reduces the risk of relapse now finds increasing support. The idea that the destructive effect of chronic inflammation in the gut is ongoing, even if patients do not have major symptoms is, however, well founded.
National guidelines that have been developed in Europe and elsewhere have mainly focused on when and how to use steroids, aminosalicylates and surgery. Only late in the course of the disease, immunosuppressants and tumour necrosis factor (TNF) blockers have been introduced rather hesitantly, even long after their advent on the market. The main concerns relate to the potential toxicity of the newer agents without paying attention to the harm caused by prolonged corticosteroid use or undertreatment. In a number of European countries there is the assumption among gastroenterologists and surgeons that TNF blockers should be offered only as an alternative to colectomy.
As the medical professionals taking care of patients with UC, we have to admit that our treatment concepts have not been very successful. Ongoing disease activity is present in ~50% of all patients with UC, colectomy rates remain high, and absence from social activities, unemployment, impaired quality of life, sick leave and disability pensions are higher in patients with UC than in the general population.
Could it be that misunderstandings and misconceptions have led to this rather unsuccessful outcome? The current paper is an attempt to list and critically review our potential misunderstandings and strategic views and to offer guidelines for more optimal care in the future.
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