More than seventy years after their initial characterisation, the aetiology of
inflammatory bowel diseases remains elusive. A recent review evaluating the incidence trends of the last 25 years concluded that an increasing incidence has been observed almost worldwide. A north-south gradient is still found in Europe. Genetic associations are variably reproduced worldwide and indicate a strong impact of environmental factors. Tumour
necrosis factor alpha (
TNF-alpha) has been shown to play a critical role in the pathogenesis of
inflammatory bowel disease (IBD).
TNF-alpha blockers are
biological agents that specifically target this key
cytokine in the inflammatory process and have become a mainstay in the
therapy of
inflammatory bowel diseases. This paper reviews the necessary investigations before using such agents, the use of such agents in pregnancy and lactation, the role of co-immunosuppression, how to monitor efficacy and safety, dose-adaptation, and the decision as to when to switch to another
TNF-alpha blocker. Finally it gives recommendations for special situations. Currently there are three
TNF-alpha blockers available for clinical use in IBD in Switzerland:
infliximab (
Remicade),
adalimumab (
Humira) and
certolizumab pegol (
Cimzia).
Infliximab is a chimeric
monoclonal antibody composed of a human
IgG1 constant region and a murine variable region and is administered intravenously.
Adalimumab is a humanised
monoclonal antibody, with both human
IgG1 constant and variable regions.
Certolizumab pegol is a pegylated, humanised monoclonal anti-TNF fragment
antigen binding fragment. Both
adalimumab and
certolizumab pegol are administered by
subcutaneous injection. The efficacy and safety of
TNF-alpha blockers in
Crohn's disease has been reviewed. The authors conclude that the three above-mentioned agents are effective in
luminal Crohn's disease. In fistulizing
Crohn's disease,
TNF-alpha blockers other than
infliximab require additional investigation.