As these reactions may herald the immunological development of neutralizing antibodies to the anti-TNF agent, some patients may develop loss of response and require modification of anti-TNF dose, dose-interval or switch to a different agent altogether. Neurological complications.  Anti-TNF therapy has been associated with development and exacerbation of both central and peripheral demyelination. However, a definite causal link has not been established.87,88 Overall, the incidence of de-novo

demyelinating disease is low.89 The α4-integrin inhibitor, natalizumab, has been associated with PML.5 Other.  Anti-TNF therapy is contraindicated in patients with NYHA class III or IV heart failure due to an increased risk of death observed in trials of these Paclitaxel agents to treat heart failure.90 Hepatic dysfunction and rarely fulminant hepatic failure have been reported with anti-TNF therapy. Psoriatic eczema is the most common dermatological side effect; however, it rarely necessitates cessation of anti-TNF therapy.58 Immunomodulator co-therapy.  The SONIC trial demonstrated that co-immunosuppression with a thiopurine and anti-TNF agent is superior selleck compound library to either agent alone for achieving and maintaining remission in

CD.91 Similar results were not shown in the COMMIT trial for co-immunosupression with anti-TNF agents and methotrexate.92 There is speculation that the addition of azathioprine, 6-mercaptopurine or perhaps methotrexate to anti-TNF reduces anti-drug antibody formation, hence boosting trough levels of the biological agent and rendering Farnesyltransferase the anti-TNF response more durable.91 This effect is not reflected in the earlier anti-TNF literature. The benefits of immunomodulator plus anti-TNF treatment must be balanced against increases in the risks of infection and lymphoma. Co-therapy of thiopurine and anti-TNF should be recommended in those with severe disease where maximal efficacy is desired. This is particularly important if few alternative medical options are available including prior loss of response or non-response to an alternative

anti-TNF agent. In UC patients receiving infliximab, co-immunosuppression with azathioprine was superior to azathioprine or infliximab monotherapy.35 Screening and prophylaxis.  History, chest X-ray and IFN-γ release assay screening for TB as well as careful historical and serological screening for potential bacterial and viral pathogens can be recommended,58,75 with subsequent immunization where appropriate. These will likely be related to local practices. Hepatitis B virus, human papilloma virus, influenza (including H1N1), and pneumococcal vaccines are all safe in those on immunosuppressive therapy.93 Live vaccines (VZV, yellow fever, measles-mumps-rubella and oral polio) should be avoided 3 weeks before and 12 weeks after anti-TNF therapy94,95 and where possible given prior to the initiation of immunosuppression.