Anti-tumor necrosis factor therapy in ulcerative colitis
- Yousif I A-Rahim, MD, PhD
Yousif I A-Rahim, MD, PhD
- Instructor of Medicine
- Harvard Medical School
- Richard J Farrell, MD
Richard J Farrell, MD
- Gastroenterology Consultant, Connolly Hospital
- Associate Clinical Professor, Royal College of Surgeons in Ireland
Tumor necrosis factor-alpha (TNF-a) has a central role in the pathogenesis of mucosal inflammation in Crohn disease. Therapy with the chimeric monoclonal antibody to TNF (infliximab) has profoundly changed the management of refractory luminal and fistulizing Crohn disease. Over two-thirds of patients with Crohn disease treated with infliximab show response to the drug whereas one-third achieve remission, and maintenance therapy has been approved on account of its glucocorticoid-sparing efficacy in refractory luminal and fistulizing Crohn disease. (See "Infliximab in Crohn disease".)
The efficacy in Crohn disease provided the rationale for clinical trials of infliximab (and other anti-TNF agents) in patients with ulcerative colitis (UC), a disorder in which TNF may also have an important role. TNF-a is expressed at high levels in the colonic mucosa of patients with UC . There is also an increased production of TNF-a by colonic lamina propria mononuclear cells and high concentrations of TNF-a in stools, rectal dialysates, and urine of patients with UC [2-5].
This topic review will focus on experience with infliximab (and other anti-TNF agents) in the management of UC . An approach to the management of UC is presented separately. (See "Management of severe ulcerative colitis in adults".)
CLINICAL TRIALS OF INFLIXIMAB
Several open-label clinical trials evaluated the efficacy of infliximab in ulcerative colitis (UC) and provided the rational for subsequent controlled trials [7-13]. At least five placebo-controlled trials of infliximab in active UC have been reported as abstracts or in final form [14-17]. A meta-analysis examined the role of infliximab in UC . Failure to achieve remission was less likely in patients treated with infliximab compared with placebo (43 versus 70 percent; RR 0.72). The meta-analysis estimated that in order to achieve one remission, four patients would need to be treated. In a network meta-analysis of seven randomized trials that compared the efficacy of biologic agents in moderate to severe UC, infliximab was more likely to induce a clinical response and mucosal healing as compared with adalimumab (OR 2.79 and 2.02, respectively) . However, this evidence needs to be interpreted with caution because it is based on indirect comparisons and there are no head-to-head trials comparing infliximab with adalimumab.
ACT 1 and ACT 2 trials — The two largest trials (ACT 1 and ACT 2, each with 364 patients) focused on patients with active ulcerative colitis treated with glucocorticoids and/or 6-mercaptopurine/azathioprine (ACT 1) or with ulcerative colitis refractory to at least one standard therapy including 5-aminosalicylic acid (5-ASA) medications, glucocorticoids, or immunosuppressants (ACT 2) .
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