Guidelines For Clinical Practice
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World J Gastroenterol. Sep 21, 2012; 18(35): 4823-4854
Published online Sep 21, 2012. doi: 10.3748/wjg.v18.i35.4823
Use of the tumor necrosis factor-blockers for Crohn's disease
Alan BR Thomson, Milli Gupta, Hugh J Freeman
Alan BR Thomson, Division of Gastroenterology, Department of Medicine, University of Western Ontario, London N6A 5A5, Canada
Milli Gupta, Department of Medicine, University of Alberta, Edmonton T6G 2X8, Canada
Hugh J Freeman, Department of Medicine, University of British Columbia, Vancouver V6T 2B5, Canada
Author contributions: Thomson ABR conceived of the need for a timely, balanced, evidence-based review, reviewed the relevant literature, provided a first draft, critiqued the clinical relevance and design of trial, revised the initial draft, and communicated with the editors; Gupta M and Freeman HJ reviewed the medical literature, critiqued the papers and meta-analyses, rewrote portions of the first draft, and approved the final document.
Correspondence to: Alan BR Thomson, Adjunct Professor, Division of Gastroenterology, Department of Medicine, University of Western Ontario, London N6A 5A5, Canada. abrthomson@gmail.com
Telephone: +1-519-6858300-35300 Fax: +1-519-6633232
Received: November 28, 2011
Revised: June 13, 2012
Accepted: August 14, 2012
Published online: September 21, 2012
Abstract

The use of anti-tumor necrosis factor-α therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn’s disease study thirty years ago. The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses. In general, it is suggested that tumor necrosis factor-α blockers (TNFBs) are indicated (1) for persons with moderately-severe Crohn’s disease or ulcerative colitis (UC) who have failed two or more causes of glucocorticosteroids and an acceptably long cause (8 wk to 12 wk) of an immune modulator such as azathioprine or methotrexate; (2) non-responsive perianal disease; and (3) severe UC not responding to a 3-d to 5-d course of steroids. Once TNFBs have been introduced and the patient is responsive, therapy given by the IV and SC rate must be continued. It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance therapy, and when or if TNFB may be weaned and discontinued. The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient’s illness needs to be confirmed. The risk/benefit profile of TNFB appears to be acceptable as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB, and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic. Because the rates of benefits to TNFB are modest from a population perspective and the cost of therapy is very high, the ultimate application of use of TNFBs will likely be established by cost/benefit studies.

Keywords: Adalimumab, Adverse effects, Certolizumab pegol, Crohn's disease, Economic evaluation, Infliximab, Secondary lack of response, Ulcerative colitis