65 High drug trough levels in the setting of treatment failure ma

65 High drug trough levels in the setting of treatment failure may be explained by alternative pathways of inflammation being responsible for the active disease (Fig. 1). Alternatively, non-inflammatory causes, such as fibrotic strictures or concurrent irritable bowel syndrome, may account for continuing symptoms. Large multicentre registries such as the TREAT registry,66 prospective cohorts67 and post marketing surveillance have provided clinicians with a combined anti-TNF experience of hundreds of thousands of patient-years. Despite the heterogeneity of these sources, they provide invaluable information regarding

safety and adverse see more events. In discussions with the patient, these risks must be weighed against the potential benefits of anti-TNF therapy. Infections.  There is increased risk of incidental infections associated with the NVP-AUY922 mouse diagnosis of IBD, associated malnutrition and the use of other immunosuppressive agents. The risk of infection is likely to be higher in patients using anti-TNF in IBD compared with other inflammatory diseases because poorly controlled intestinal ulceration provides a ready source of intra-abdominal

sepsis. Anti-TNF agents also convey a risk of opportunistic infections, among which tuberculosis (TB) is the most clearly associated. TNF is a key cytokine involved in maintenance of granulomatous compartmentalization of Mycobacterium tuberculosis.68 The risk of infection increases with the use of corticosteroids, narcotic analgesics, disease severity, thiopurines, and anti-TNF agents. The odds ratio for opportunistic

infections when using anti-TNF agents is approximately fourfold (Table 2).69 The risk increases strikingly to 14.5 when combination therapy with two or three agents is given. These figures, however, can be contrasted to other studies quoting minimal increased risk of opportunistic MCE infection for those on infliximab monotherapy.67 Combination therapies that include corticosteroids appear to be those that result in the highest risk of opportunistic infections.69 Activation of latent TB and acquisition of primary TB are both more likely in patients treated with anti-TNF agents.70 Post-marketing reports suggest a fourfold increase in the risk of TB illness.68 Screening for TB prior to commencing anti-TNF therapy provides a 74% reduction in TB rates.71 In addition to a meticulous history and a chest X-ray, an interferon-γ (IFN-γ) release assay (such as QuantiFERON-TB Gold assay) or tuberculin skin test (> 1 cm Mantoux wheal) isused for TB screening.72 IFN-γ release assays are not reactive against Bacillus Calmette-Guérin (BCG) vaccines and hence are more specific.73 Specific management of established or suspected latent TB infection is covered elsewhere.

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