Infliximab Induces and Maintains Mucosal Healing in Ulcerative Colitis Patients

Mucosal healing (MH) has emerged as an important treatment goal for patients with IBD. Historically, the therapeutic goals of induction and maintenance of clinical remission seemed insufficient to change the natural history of IBD. Evidence has now accumulated to show that MH can alter the course of IBD, as it is associated with sustained clinical remission, and reduced rates of hospitalization and surgical resection. In patients with ulcerative colitis, MH may represent the ultimate therapeutic goal because inflammation is limited to the mucosa. In patients with Crohn's disease, which is a transmural disease, MH could be considered as a minimum therapeutic goal. This Review focuses on the definition of MH and discusses the ability of each available IBD medication to induce and maintain MH. The importance of achieving MH is also discussed and literature that demonstrates improvement of disease course with MH is reviewed. Finally, we discuss how best to integrate the treatment end point of MH into clinical practice for the management of patients with IBD.

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Clinical implications of mucosal healing for the management of IBD

Chambrun

Peyrin–Biroulet

Lémann

et al. 2009

Nat Rev Gastroenterol Hepatol

416

254

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How Rapidly Should Remission Be Achieved?

Isaacs

2010

Dig Dis

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The major goal of therapy in inflammatory bowel disease is to induce remission. Remission has multiple definitions – clinical remission, where the patient’s symptoms have remitted, and endoscopic remission, in which there has been complete mucosal healing. Mucosal healing is a harder endpoint of remission but may be more difficult to achieve. In clinical trials we are forced to use activity indices such as the Crohn’s disease activity index that may not completely reflect the endoscopic and histologic state of the bowel. Ideally we would like to see remission as quickly as possible to improve patient quality of life. The time to remission varies between different therapeutic approaches. Steroids tend to have a rapid clinical effect with remission seen in some patients as early as two weeks. In early anti-TNF trials, a single dose of infliximab lead to 27% remission at two weeks compared to 4% of placebo patients. Adalimumab and certolizumab have similar reports of early induction of remission. Mesalamine in Crohn’s disease has inconsistent and delayed remission rates, whereas in ulcerative colitis, response and remission rates are more consistent in the three-week time frame. Azathioprine and 6-mercaptopurine have delayed onset of action but may induce remission as early as six weeks if dosing is optimized. In this presentation induction of clinical remission and mucosal healing in Crohn’s disease and ulcerative colitis will be discussed. The impact of early remission on disease course will also be reviewed.

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Lessons to Learn from Crohn's Disease Clinical Trials: Implications for Ulcerative Colitis

Jauregui-Amezaga¹,

Ricart²,

Panés

2011

CDT

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The perception that Crohn's disease is a more severe process than ulcerative colitis, led to the initial development of a majority drugs, and testing of treatment strategies, in the former. In the absence of similar studies in ulcerative colitis, information of Crohn's disease studies may help the clinician in decision making in UC. Studies on aminosalicylates show that drugs with a topical effect which are not effective in Crohn's disease may still have efficacy in ulcerative colitis, and this should be considered in future drug development. The best efficacy of corticorteroids is achieved with high doses of 1 mg/kg/day, and reaching remission may be delayed by several weeks, although non-response in the initial days should lead to treatment escalation, in particular in severe patients. Thiopurines have a steroid-sparing effect, and the duration of treatment should be at least 4 years; caution should be exerted in using these drugs in EBV negative young patients and in the older population for the risk of lymphoma. Anti-TNF monoclonal antibody therapy is optimized by use of induction followed by scheduled maintenance as opposed to episodic treatment, resulting in higher sustained response rates and lower immunogenicity. Associations of non-biological immunosuppressants with anti-TNF antibodies can further increase therapeutic efficacy maintaining a safe profile. Patients under combined therapy with sustained clinical and biological remission and mucosal healing may be candidates to stop anti-TNF treatment. The majority of these recommendations need to be specifically studied in patients with ulcerative colitis before generalization in clinical practice.

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Infliximab Induces and Maintains Mucosal Healing in Ulcerative Colitis Patients

Cited by 3 publications

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Clinical implications of mucosal healing for the management of IBD

Clinical implications of mucosal healing for the management of IBD

How Rapidly Should Remission Be Achieved?

Lessons to Learn from Crohn's Disease Clinical Trials: Implications for Ulcerative Colitis

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