Cancer in Crohn's Disease Patients Treated with Infliximab: A Long-term Multicenter Matched Pair Study

GI Unit, University, Tor Vergata, Roma.
Inflammatory Bowel Diseases (Impact Factor: 4.46). 03/2011; 17(3):758-66. DOI: 10.1002/ibd.21416
Source: PubMed


The long-term risk of neoplasia in Crohn's disease (CD) patients treated with infliximab is undefined. The aim was to assess, in a multicenter, matched-pair study, whether infliximab use in CD is associated with an increased frequency of neoplasia in the long term.
A multicenter, long-term, matched-pair study was conducted in 12 referral inflammatory bowel disease (IBD) centers. An initial cohort of 808 CD patients, including 404 infliximab-treated (CD-IFX) and 404 matched CD controls never treated with infliximab (CD-C) studied from 1999 to 2004, was followed up for an additional 4 years (2004-2008). Cases and controls were matched for: sex, age (±5 years), CD site, follow-up (±5 years), immunosuppressant use, and CD duration (±5 years). From 1999 to 2008 the frequency and characteristics of neoplasia were compared between CD-IFX and CD-C.
In 2008, 591 patients (304 CD-IFX, 287 CD-C) were in follow-up. Matched couples included 442 patients: 221 CD-IFX and 221 CD-C (median follow-up, months: 72, range 48-114 versus 75, range 44-114). From 1999 to 2008 the frequency of neoplasia among the 591 patients did not differ between CD-IFX (12/304; 3.94%) and CD-C (12/287; 4.19%; P = 0.95). A comparable frequency of neoplasia was also observed between the 221 matched couples (CD-IFX: 8/221; 3.61% versus CD-C: 9/221; 4.07%; P = 1). No specific histotype of cancer appeared associated with infliximab use.
The frequency of neoplasia was comparable in an adult population of CD patients treated or not with infliximab, matched for clinical variables and followed up for a median of 6 years.

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Available from: Claudio Papi, Dec 30, 2013
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    • "Over the past 10 years, anti-TNF agents including infliximab have been emerging as an alternative treatment to overcome the shortcomings of conventional drugs and provide most of IBD patients the improved life quality. However, several side effects associated with infliximab have been recently reported (Table 2), including acute or delayed infusion reactions, leucopenia, serious infection, antichimeric antibody formation, and increased risk of malignancy [42–47, 89]. Steenholdt et al. showed that acute severe infusion reactions were strongly associated with development of anti-infliximab IgG antibody, and the risk was particularly high at the 2nd infusion in retreatment series [42]. "
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    ABSTRACT: The pathogenesis and treatment of inflammatory bowel disease (IBD) have been recently advanced, while it is still challenged with high morbidity and poor prognosis. Infliximab, a monoclonal antibody of tumor necrosis factor (TNF), has emerged as an efficient treatment with many clinical benefits such as quick disease activity reduction and IBD patient life quality improvement. However, the biological effects of infliximab on IBD need to be elucidated. This paper reviewed the clinical use and recently advanced biological action of infliximab on IBD. By forming the stable complex with the soluble or the membrane form of TNF in fluid environment or on cell surface of immune cell, fibroblast, endothelium, and epithelium, infliximab quenches TNF activity and performs the important biological actions which lead to amelioration and remission of immune responses. The mechanisms of infliximab treatment for IBD were intensively discussed. The recent advances on two topics including predictors and side effects of infliximab treatment were also reviewed.
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    • "A recent multicenter, matched-pair study assessed whether IFX use in CD for a median of 6 years is associated with an increased frequency of neoplasia in the long term. The authors concluded that the frequency of neoplasia was comparable in an adult population of CD patients treated or not with IFX.52 Toxicity can be significantly reduced by routine tuberculosis screening, and by avoiding anti-TNF agents in patients with heart failure, chronic infections, or previous neoplastic disease. Prospective, observational studies with longer follow-up, such as the TREAT registry,53 will continue to provide more useful information on this issue, and clinicians need to remain aware of the potential for serious adverse events during longer-term exposure beyond the confines of clinical trials. "
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