Update on the Management of Ulcerative Colitis (original) (raw)
Related papers
Biological therapy for ulcerative colitis
Gastroenterology report, 2014
Ulcerative colitis (UC) is a major form of inflammatory bowel disease (IBD) worldwide. Better understanding of the pathogenesis of UC has led to the development of novel therapeutic agents that target specific mediators of the inflammatory cascade. A number of biological agents have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of UC and several more are currently in various phases of drug development. The commonly used agents include TNFα antagonists (e.g. infliximab, adalimumab, and golimumab) and anti-integrin agents (vedolizumab). These biological agents have profoundly influenced the management of UC patients, especially those with refractory disease. This paper reviews the currently available knowledge and evidence for the use of various biological agents in the treatment of UC.
REVIEW ARTICLE Update on the Management of Ulcerative Colitis
2012
The present treatment goals for inflammatory bowel diseases (IBD) especially ulcerative colitis (UC) include rapid induction of clinical remission, steroid-free maintenance of clinical remission, mucosal healing and improvement of quality of life in UC patients. Immunomodulators have been reserved for steroid-dependent or steroid-refractory UC patients. Among these agents, azathioprine/6-mercaptopurine should be used for maintenance of remission in quiescent UC. Calcineurin inhibitors can be prescribed as a short-term rescue therapy in steroid-refractory UC patients, but the long term efficacy of these agents remains unclear. According to retrospective studies, methotraxate is not recommended for inducing and maintaining remission in UC. Novel biological therapies targeting different specific immunological pathways continue to be developed and introduced for a variety of clinical scenarios in IBD. Infliximab is currently used for induction and maintenance therapy in patients who hav...
Promising effect of infliximab on the extent of involvement in ulcerative colitis
Journal of Research in Medical Sciences the Official Journal of Isfahan University of Medical Sciences, 2011
BACKGROUND:Ulcerative colitis (UC) is a disabling disease with increasing incidence in Iran. In spite of combined medical therapy, some patients eventually undergo total colectomy. Infliximab has proved itself as a rescue therapy and even as an early aggressive therapy for severe extensive UC. Meantime, there are concerns about its complications. The aim of this study was to evaluate the efficacy of infliximab in Iranian refractory UC patients.METHODS:This multi centric case-series study included 29 UC patients receiving two to three of the drugs prednisolone, AZT/6MP and 5ASA but yet having flare-ups. At first, the extent of colon involvement was determined by colonoscopy; then the drug was administered at baseline, 2nd week and 6th week and colonoscopy repeated afterwards. Clinical and laboratory data were also recorded.RESULTS:In first endoscopy 18 patients (62%) out of 29 suffered from pancolitis and none had normal results. In second examination (done on 19 patients), one was normal and only 8 of 18 (27.6%) had pancolitis. Considering missing cases, at least in 33.3% of patients the drug has reduced the extreme extent of colon involvement. Also a wilcoxon signed ranks test revealed significant reduction of the disease extension after this treatment (p = 0.008). There were only one leucopenic and one hypotensive reactions in short term. The drug showed effectiveness in the term of disease modifying, too.CONCLUSIONS:These data show the usefulness of the drug in refractory UC. Longer follow ups and controlled trials are needed.
Biologic therapy in inflammatory bowel disease
PubMed, 2013
In luminal Crohn's disease with moderate to severe inflammatory activity, infliximab and adalimumab can be used in the case of treatment failure with conventional therapies, such as systemic steroids and immunosuppressive therapy or if this treatment is not tolerated. Further treatment strategy depends on the primary response to induction therapy. Effect of maintenance therapy should be evaluated clinically and paraclinically at least every 26-52 weeks, and maybe supplemented by endoscopy or MRI scan. Decision of treatment discontinuation is based on disease manifestation, treatment response and paraclinical parameters. In fistulising Crohn's disease, treatment with infliximab or adalimumab can be initiated in simple fistula with rectal inflammation or complex fistula when the initial treatment has insufficient effect. Further treatment strategy depends on the primary response to induction therapy. Maintenance therapy is often necessary in complex fistulas. Treatment efficacy and possible discontinuation of treatment is evaluated at least every 26-52 weeks - if possibly with diagnostic imaging. In acute severe ulcerative colitis, treatment with infliximab can be used in patients with partial response after 3-5 days of treatment with a high-dose systemic steroid and when surgical treatment is not preferred or required. Further treatment strategy depends on the response to the first drug administration and colectomy should always be considered as an option. Effect of subsequent initiated maintenance therapy should be evaluated at least every 26-52 weeks on the basis of symptoms, clinical markers, paraclinical parameters and possibly by endoscopy. In chronic active ulcerative colitis, infliximab and adalimumab can be used in the case of treatment with immunosuppressive therapy fails and if surgery is not preferred. Further treatment strategy depends on the response to induction therapy. Treatment efficacy is assessed by symptoms, clinical markers, paraclinical parameters and possibly by endoscopy. Effect of maintenance therapy should be evaluated at least every 26-52 weeks. During treatment with biologic drugs focus should be on possible complications, such as infections, infusion or injection reactions and dermatological side effects. An overview of levels of evidence and recommendations is presented.
Biologic therapies in inflammatory bowel disease
Translational Research, 2014
Inflammatory bowel disease, including its 2 entities ulcerative colitis and Crohn's disease, is a chronic medical condition characterized by the destructive inflammation of the intestinal tract. Biologics represent a class of therapeutics with immune intervention potential. These agents block the proinflammatory cascade that triggers the activation and proliferation of T lymphocytes at the level of the intestine, therefore reestablishing the balance between the pro-and anti-inflammatory messages. All 7 biologics showing clinical benefits in inflammatory bowel disease are monoclonal antibodies. The following systematic review discusses the pharmacokinetics and efficacy of the tumor necrosis factor blockers infliximab, adalimumab, certolizumab pegol, and golimumab. In addition, we describe the a 4 integrin inhibitors natalizumab and vedolizumab, which are directed against cell adhesion molecules, as well as the interleukin 12/23 blocker ustekinumab. (Translational Research 2014;-:1-24) Abbreviations: ADA ¼ antidrug antibodies; ADM ¼ adalimumab; AUC ¼ area under the curve; CD ¼ Crohn's disease; CI ¼ confidence interval; C max ¼ maximum concentration; C trough ¼ trough concentration; CZP ¼ certolizumab pegol; GLM ¼ golimumab; HR ¼ hazard ratio; IBD ¼ inflammatory bowel disease; IFX ¼ infliximab; IP ¼ induction phase; MP ¼ maintenance phase; NTZ ¼ natalizumab; OR ¼ odds ratio; RR ¼ relative risk; t 1/2 ¼ half-life; T max ¼ time to maximum concentration; TNF ¼ tumor necrosis factor; UC ¼ ulcerative colitis; UTK ¼ ustekinumab; VDZ ¼ vedolizumab I nflammatory bowel disease (IBD) is a medical condition characterized by the intermittent destructive inflammation of the intestinal tract. Ulcerative colitis (UC) affects only the intestinal mucosa, whereas Crohn's disease (CD) affects all layers of the intestinal wall. CD is characterized histologically by transmural inflammation with asymmetrical and discontinuous granulomas, and focal lymphoid hyperplasia leading to fibrosis of the intestinal wall. On the contrary, the histologic picture of UC presents inflammation limited to the intestinal mucosa with proportioned continuous crypt abscesses and polymorphonuclear leukocyte
Cureus
Biologics have been emerging as promising therapies in ulcerative colitis (UC) patients who are refractory to conventional medical treatment. This literature review aims to appraise the existing evidence on the efficacy and safety of NICE approved biological therapies, of which there are currently five licensed drugs, available for the treatment of UC in adults. An initial search was performed using National Institute of Clinical Excellence (NICE) guidelines. A further literature search of EMBASE, MEDLINE, Science Direct and Cochrane Library databases was done, resulting in a total of 62 studies being included in this review. Recent and seminal papers were included. Inclusion criteria for this review were adult participants and English papers only. In most studies, anti-tumour necrosis factor ɑ (TNFɑ) naïve patients were found to have improved clinical outcomes. Infliximab was found to be highly effective in inducing short-term clinical response, clinical remission as well as mucosal healing. However, loss of response was common and dose escalation was often required for achievement of long-term efficacy. Adalimumab was found to have both short-term and longterm efficacy which was also supported by real-world data. Golimumab was shown to have comparable efficacy and safety profiles to other biologics, although lack of therapeutic dose monitoring and loss of response is a barrier to optimising golimumab treatment efficacy. Vedolizumab was shown to have higher clinical remission rates when compared to adalimumab in a head-to-head trial, and the most cost-effective biologic when calculating quality-adjusted life years. Ustekinumab was found to significantly improve clinical remission rates in UC patients who were previously unresponsive to other biological treatments. However, as this is a newly licensed drug, there is limited literature currently available. Further, head-to-head studies are required to help determine the optimal treatment for patients with UC. With patents expiring, the development of biosimilars will help to reduce costs and increase the availability of these drugs to patients.
Current Strategies for the Treatment of Ulcerative Colitis
Recent Patents on Inflammation & Allergy Drug Discovery, 2009
Ulcerative colitis (UC) is a chronic, relapsing and debilitating idiopathic inflammation of the gastrointestinal tract. Dysregulation of the mucosal immune response toward commensal bacterial flora together with genetic and environmental factors plays an important role in the pathogenesis. Refractory UC refers to disease that does not respond to or responds poorly to the many drugs used to treat the disease. The aim of medical treatment is to induce and maintain clinical remission. The most commonly used drugs, including mesalazine, azathioprine, 6-mercaptopurine, cyclosporine, and more recently anti-tumor necrosis factor (TNF) monoclonal antibody (e.g., infliximab), are chosen to suppress the immune system in intestinal mucosa. Additionally, colectomy may be required if medical treatments are unsuccessful or if complications develop. Some of the recent patent related to the field also discuss in this review article.