© 2009 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY nature publishing group 1575 REVIEW CLINICAL REVIEWS INTRODUCTION In the past decade, infliximab (IFX), a chimeric monoclonal anti-tumor necrosis factor (anti-TNF)-  antibody, has been used worldwide to treat more than 1 million patients affected by inflammatory bowel disease (IBD), such as Crohn ’s dis- ease (CD) and ulcerative colitis (UC), as well as rheuma- tologic and dermatological diseases such as rheumatoid arthritis (RA), ankylosing spondilytis, psoriatic arthritis, and psoriasis. However, IFX has a number of well-known contraindications and some concerns about its safety have arisen, including the risk of developing malignancies and severe infections (see Tables 1 and 2). us, physicians who prescribe IFX should know the correct indications for its use and be aware of the most frequent undesirable events to prevent their occurrence or manage such events should they arise. Indeed, to minimize the occurrence of side effects, which may be severe or even life threatening, several recommendations and guidelines have been proposed and published by important scientific societies (1–5). However, some issues remain unresolved and their solutions are not clear. In this clinical review, we focused on the most fre- quent and potentially severe latent or chronic infections that may reactivate during IFX therapy. We also examined the use of IFX in pregnancy because IBD patients are mostly in the reproductive age; thus, physicians frequently face this issue. Finally, we considered the risk of the occurrence of malignancies in IFX-treated patients and the possibility of IFX use in patients with previous cancer or preneoplastic disease. en, the aims of this paper are (1) to review the most recent studies on the diagnosis and treatment of latent tuberculosis infection (LTBI) in IBD patients before start- ing IFX; (2) to define the risk of reactivation of hepatitis B and C infection during IFX therapy and present current strategies for reducing this occurrence; and (3) to assess the possibility and limits on the use of IFX in special patients (e.g., pregnant patients, or patients with malignancy or pre-neoplastic lesions) and to provide practical tips for managing such patients. METHODS To perform this review, published papers up to Septem- ber 2008, including electronic publications available ahead of print, were identified through searches in the MEDLINE and EMBASE electronic databases. To identify relevant pub- lications for this review, we used the search terms “inflixi- mab” OR “anti-TNF- ” AND “inflammatory bowel disease” OR “Crohn’s disease” OR “ulcerative colitis” in combination with the following words: “latent tuberculosis, ” “ Mycobacte- rium tuberculosis,” “tuberculin skin test,” “interferon-gamma Use of Infliximab in Particular Clinical Settings: Management Based on Current Evidence Alfredo Papa, MD 1 , Giammarco Mocci, MD 1 , Michele Bonizzi, MD 1 , Carla Felice, MD 1 , Gianluca Andrisani, MD 1 , Italo De Vitis, MD 1 , Luisa Guidi, MD 1 and Antonio Gasbarrini, MD 1 With the increasingly widespread use of the anti-tumor necrosis factor- a agent infliximab for the treatment of Crohn’ s disease and ulcerative colitis, there have been some concerns raised about the potential consequences of such therapy in particular clinical settings. In this review, we report the current strategies for optimizing treatment outcomes and minimizing the risks of some of the most serious events attributable to infliximab therapy. In particular, an up-to-date overview is provided on how to treat patients with inflammatory bowel disease using infliximab therapy, with regard to the diagnosis and management of latent tuberculosis infection and the risk of reactivation of hepatitis B and C infections. Furthermore, based on the available evidence, we evaluate the possibility of using infliximab during pregnancy. Finally, we evaluate whether patients with malignancies or pre-neoplastic lesions could be candidates for infliximab therapy. Overall, this review will provide physicians who use infliximab for the treatment of inflammatory bowel disease with several practical recommendations for the management of some complex situations that may occur in daily clinical practice. Am J Gastroenterol 2009; 104:1575–1586; doi:10.1038/ajg.2009.162; published online 28 April 2009 1 Gastroenterology Unit, Department of Internal Medicine, Catholic University of Rome, Rome, Italy. Correspondence: Alfredo Papa, MD, Istituto di Medicina Interna e Geriatria, Policlinico A. Gemelli, Università Cattolica del S. Cuore, L.go A. Gemelli, 8 00168 Rome, Italy. E-mail: apapa@rm.unicatt.it Received 29 October 2008; accepted 4 February 2009