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Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 021205, USA.
Alimentary Pharmacology & Therapeutics (Impact Factor: 4.55). 06/2009; 30(3):253-64. DOI: 10.1111/j.1365-2036.2009.04037.x
Source: PubMed

ABSTRACT There remain concerns about the safety of infliximab therapy in patients with inflammatory bowel disease (IBD).
To assess the association between the initiation of infliximab and other immunomodulating drugs and the risk of serious bacterial infection in the treatment of IBD.
We assembled a cohort study of patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC). All patients initiating an immunomodulating drug between January 2001 and April 2006 were identified in British Columbia from linked health care utilization databases. Exposure of interest was initiation of infliximab or corticosteroids compared with initiation of other immunosuppressive agents, including azathioprine, mercaptopurine (MP) and methotrexate (MTX). Outcome of interest was serious bacterial infections requiring hospitalization, including Clostridium difficile.
Among 10 662 IBD patients, the incidence rate of bacteriaemia ranged from 3.8 per 1000 person-years (95% confidence interval 2.1-6.2) for other immunosuppressive agents to 7.4 (3.3-19.3) for infliximab with slightly higher rate for serious bacterial infections resulting in an adjusted relative risk 1.4 (0.47-4.24). Clostridium difficile infections occurred in 0/1000 (0-5.4) among 521 infliximab initiations and 14/1000 (10.6-18.2) for corticosteroids. Corticosteroid initiation tripled the risk of C. difficile infections (RR = 3.4; 1.9-6.1) compared with other immunosuppressant agents. This corticosteroid effect was neither dose-dependent nor duration-dependent. Bacteriaemia and other serious bacterial infections were not increased by corticosteroids or infliximab (5 events).
In a population-based cohort of patients with IBD, we found no meaningful association between infliximab and serious bacterial infections, although some subgroups had few events. Corticosteroid initiation increased the risk for C. difficile infections in these patients.

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