Managing Chronic Unremitting Ulcerative Colitis
Background Chronic active ulcerative colitis (UC) is associated with significant morbidity, loss of productivity, increased colorectal cancer risk and cost. Up to 18% of patients suffer chronic active disease, with 30% requiring colectomy at 10 years. The management remains challenging given the relatively few clinical trials in this area.
Aim To summarise the evidence regarding optimal management strategies for patients with chronic active UC of differing disease extents and degrees of treatment refractoriness.
Method A literature search using the PubMed and Medline databases was performed. No time limit was set on article publication for inclusion.
Results The principles of management should focus on confirming disease activity, exclusion of alternative diagnoses, adherence and treatment escalation. Infliximab and topical tacrolimus are options in refractory proctitis, although the evidence for these therapies is limited. Both infliximab and adalimumab are effective in corticosteroid-refractory disease, although the proportions of patients achieving corticosteroid-free remission remain modest (24% at 30 weeks and 16.9% at 8 weeks respectively). Alternatives include ciclosporin and tacrolimus, and possibly methotrexate. Colectomy often leads to an improved quality of life; medical strategies unlikely to provide durable corticosteroid-free remission should not be pursued.
Conclusions No current pharmacological treatment delivers mucosal healing in the majority of patients. Newer treatments such as vedolizumab and tofacitinib may represent valuable future therapies. Available medical options should be discussed with patients at every step of their management, with an honest appraisal of the evidence. Surgery should always be considered in patients with chronic refractory disease of any extent.
Ulcerative colitis (UC) is a chronic relapsing and remitting inflammatory disease of the colon, mostly affecting the young and middle-aged, which generally requires lifelong treatment. The prevalence in the UK is approximately 243 per 100 000 of the population, with an increasing global incidence since the mid-twentieth century across many ethnic and racial groups in the developed world.
Chronic active disease has a significant impact on patient's lives. Health-related quality of life scores are reduced significantly in patients with active UC compared with those with quiescent disease and the background population. Patients with chronic active UC report a significantly greater negative impact of the disease on their lives compared with patients with other chronic conditions such as rheumatoid arthritis, asthma and migraine. In addition, work productivity is adversely affected: pan-European patient surveys have found that 65% of patients with UC felt that the condition impaired their ability to undertake their job, with symptoms causing a change in job or altered job responsibilities in 28%. The majority of respondents to the European Federation of Crohn's and Ulcerative Colitis Associations IMPACT survey had taken time off work during the previous year, with 26% of these having been away from work for 25 days or more. Thus, the total annual economic burden of UC has been estimated to be as high as $14.9 billion in the US and €29.1 billion in Europe in a recent systematic review.
Furthermore, although the magnitude of relative risk has been debated, patients with UC have a higher risk of developing colorectal cancer than the general population. This risk is related to the duration and inflammatory burden of the disease. Longitudinal follow-up data have shown colectomy rates for patients with extensive colitis at 10 years to be in the order of 30%, with relapsing disease noted in 83% of patients at 10 years follow-up. Finally, patients are exposed to complications of treatment as well as those of the underlying condition. These include the well-known side effects of chronic glucocorticoid usage, and the increased risk of development of lymphoma and nonmelanoma skin cancers with immunosuppressive treatment.
The majority of the issues discussed above are related to chronic disease activity. Longitudinal studies have suggested that almost 10% of patients experience a chronic continuous phenotype of disease activity and up to 18% of patients suffer chronic disease activity every year up to 7 years after diagnosis. In addition, colectomy rates at 10 years for patients with chronic active disease appear to be up to three times higher than all UC patients overall. No therapy has delivered clinical remission or mucosal healing in all patients, although the achievement of mucosal healing has been associated with improved clinical symptoms and a reduced colectomy rate. In addition, national audits have demonstrated a wide variation in clinical practice with a striking underutilisation of available therapies. Therefore, the management of patients with unremitting UC remains a challenge. The aims of this review are to provide an overview of the management of chronic unremitting UC and discuss the evidence behind its medical management. Reference will be made to recent UK and European guidelines, as well as previous US guidelines, which have provided comprehensive reviews of the literature.
Abstract and Introduction
Abstract
Background Chronic active ulcerative colitis (UC) is associated with significant morbidity, loss of productivity, increased colorectal cancer risk and cost. Up to 18% of patients suffer chronic active disease, with 30% requiring colectomy at 10 years. The management remains challenging given the relatively few clinical trials in this area.
Aim To summarise the evidence regarding optimal management strategies for patients with chronic active UC of differing disease extents and degrees of treatment refractoriness.
Method A literature search using the PubMed and Medline databases was performed. No time limit was set on article publication for inclusion.
Results The principles of management should focus on confirming disease activity, exclusion of alternative diagnoses, adherence and treatment escalation. Infliximab and topical tacrolimus are options in refractory proctitis, although the evidence for these therapies is limited. Both infliximab and adalimumab are effective in corticosteroid-refractory disease, although the proportions of patients achieving corticosteroid-free remission remain modest (24% at 30 weeks and 16.9% at 8 weeks respectively). Alternatives include ciclosporin and tacrolimus, and possibly methotrexate. Colectomy often leads to an improved quality of life; medical strategies unlikely to provide durable corticosteroid-free remission should not be pursued.
Conclusions No current pharmacological treatment delivers mucosal healing in the majority of patients. Newer treatments such as vedolizumab and tofacitinib may represent valuable future therapies. Available medical options should be discussed with patients at every step of their management, with an honest appraisal of the evidence. Surgery should always be considered in patients with chronic refractory disease of any extent.
Introduction
Ulcerative colitis (UC) is a chronic relapsing and remitting inflammatory disease of the colon, mostly affecting the young and middle-aged, which generally requires lifelong treatment. The prevalence in the UK is approximately 243 per 100 000 of the population, with an increasing global incidence since the mid-twentieth century across many ethnic and racial groups in the developed world.
Chronic active disease has a significant impact on patient's lives. Health-related quality of life scores are reduced significantly in patients with active UC compared with those with quiescent disease and the background population. Patients with chronic active UC report a significantly greater negative impact of the disease on their lives compared with patients with other chronic conditions such as rheumatoid arthritis, asthma and migraine. In addition, work productivity is adversely affected: pan-European patient surveys have found that 65% of patients with UC felt that the condition impaired their ability to undertake their job, with symptoms causing a change in job or altered job responsibilities in 28%. The majority of respondents to the European Federation of Crohn's and Ulcerative Colitis Associations IMPACT survey had taken time off work during the previous year, with 26% of these having been away from work for 25 days or more. Thus, the total annual economic burden of UC has been estimated to be as high as $14.9 billion in the US and €29.1 billion in Europe in a recent systematic review.
Furthermore, although the magnitude of relative risk has been debated, patients with UC have a higher risk of developing colorectal cancer than the general population. This risk is related to the duration and inflammatory burden of the disease. Longitudinal follow-up data have shown colectomy rates for patients with extensive colitis at 10 years to be in the order of 30%, with relapsing disease noted in 83% of patients at 10 years follow-up. Finally, patients are exposed to complications of treatment as well as those of the underlying condition. These include the well-known side effects of chronic glucocorticoid usage, and the increased risk of development of lymphoma and nonmelanoma skin cancers with immunosuppressive treatment.
The majority of the issues discussed above are related to chronic disease activity. Longitudinal studies have suggested that almost 10% of patients experience a chronic continuous phenotype of disease activity and up to 18% of patients suffer chronic disease activity every year up to 7 years after diagnosis. In addition, colectomy rates at 10 years for patients with chronic active disease appear to be up to three times higher than all UC patients overall. No therapy has delivered clinical remission or mucosal healing in all patients, although the achievement of mucosal healing has been associated with improved clinical symptoms and a reduced colectomy rate. In addition, national audits have demonstrated a wide variation in clinical practice with a striking underutilisation of available therapies. Therefore, the management of patients with unremitting UC remains a challenge. The aims of this review are to provide an overview of the management of chronic unremitting UC and discuss the evidence behind its medical management. Reference will be made to recent UK and European guidelines, as well as previous US guidelines, which have provided comprehensive reviews of the literature.
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