0938 Tumour necrosis factor (TNFα) blockers and serious fungal infections

The risk vs benefits arguments mentioned in the previous summary in relation to HPV vaccines also apply to adverse events recorded for drugs such as TNF blockers. However there is perhaps an important difference: in the case of the vaccine one is considering the risk of an adverse event vs the possibility of a significant disease or condition i.e. two unknowns. On the other hand, when considering a TNF blocker one is almost certainly dealing with patients with an advanced or refractory stage of conditions such as rheumatoid arthritis or inflammatory bowel disease, and one might guess that such patients would fairly willingly trade the relief offered by the drug for the relatively low risk of a serious adverse effect. However, even if that argument succeeds, there is an obligation on patients, manufacturers, healthcare providers and drug monitoring agencies to report adverse events, and for those on the supply side to make appropriate recommendations. Along these lines, healthcare professionals have received communications from the manufacturers of etanercept and infliximab, warning of the risk of invasive and potentially-fatal fungal infections, and advising of the need for vigilance, recognition of clinical signs and active intervention. Package inserts are being modified accordingly. Nevertheless one might question why it has taken this long to react. The existing etanercept side effects list includes a warning of serious infections, but the same cannot be said for infliximab. This is surprising given that a 2005 article discusses the putative role of the pro-inflammatory cytokine in host defence and expresses concern around consequences of blocking this action. The article mentions the numerous reports of adverse events, stating that most were related to infliximab, but etanercept and adalimumab may also be associated with an increased risk of TB, histoplasmosis, listeriosis, aspergillosis, coccidioidomycosis and candidiasis. More-recent articles address the subject, commenting on the possible role of steroids in rendering patients susceptible to the infections. Review of reports between 1996 and 2007 revealed 281 cases: 80% were associated with infliximab, 16% with etanercept and 4% with adalimumab. Those associated with infliximab occurred at a median of 55 days after initiation of therapy, whereas with etanercept the time interval was around 144 days. Use of at least one other immunosuppressive , typically a systemic steroid, was reported during the course of the fungal infection in 98% of the 104 for whom data were available. Histoplasmosis, candidiasis and aspergillosis occurred with similar frequency (23-30%).

Read more:
Wyeth and Schering Plough medicine safety alerts: September 2009-10-10
Pharmacotherapy 2005; 25: 1181-92
Mayo Clin Proc 2008; 83: 181-94
Topic: TNF suppression & consequences