The risk of infections such as this is difficult to calculate based on current evidence, and management is discussed below. Malignancy.  A small but relevant increase in the AP24534 nmr risk of lymphoma is associated with anti-TNF therapy. The extent

to which this risk is attributable to anti-TNF therapy or to the use of other immunomodulators is unknown.76,77 A meta-analysis examining lymphoma risk associated with anti-TNF agents across 26 studies and over 21 000 patient-years of follow up identified a relative risk of 3.2 compared with standardized incidence rates, and 1.7 compared with other immunomodulator use alone.78 Similar results were not noted with the TREAT registry data,66 which demonstrated no increased risk of lymphoma among infliximab-treated patients. It should be acknowledged that these agents have only been in widespread use for 10 years and any long term risk may not yet be apparent. Hepatosplenic T-cell lymphoma is a rare but almost universally fatal malignancy. Talazoparib mouse Prior to anti-TNF therapy only around 150 reports of this rare lymphoma had been

published, predominantly in young males (several in IBD patients treated with thiopurines). Since the introduction of anti-TNF agents, 14 cases have occurred in patients receiving infliximab and three with adalimumab.79 This rare complication may be more strongly associated with the use of thiopurines rather than anti-TNF. Concerns over this has led to the use of anti-TNF monotherapy or replacing thiopurines with methotrexate particularly in young males. However, overemphasis on the unquantifiably rare risk of hepatosplenic SPTLC1 T-cell lymphoma should be avoided when considering the benefits of treatment especially in those with severe CD.80 Evidence is conflicting regarding the risk of non-lymphoma malignancies during anti-TNF therapy. There are no reports of increased risk of malignancy in some series,66,81 but one meta-analysis examining RA patients on anti-TNF therapy identified a threefold increase in malignancies, particularly including skin cancer and lymphoma.82 Autoimmune disease.  Anti-nuclear

antibody (ANA) and double-stranded (ds)-DNA can become positive following anti-TNF therapy. After 24 months of infliximab therapy,83 50% of patients showed ANA positivity; this phenomenon also occurs in adalimumab therapy. The clinical significance of an isolated positive ANA is minimal. Lupus-like syndromes involving rash, arthritis or glomerulonephritis occur rarely.83–85 Infusion reactions/injection site reactions.  Injection site reactions (with adalimumab and certolizumab pegol) and infusion reactions (to infliximab) affect 10% of patients. Typically they are mild and can be managed by slowing the infusion and administering corticosteroids, antihistamines and paracetamol. Premedication with these agents, and co-administration of immunosuppressive agents is used for secondary prophylaxis. Anaphylactic reactions occur in less than 1% of infusions.