by Dr Jacqueline Gosink
Tumour necrosis factor (TNF) inhibitors are increasingly used to treat chronic inflammatory bowel diseases, rheumatic diseases and psoriasis. Continuous drug level monitoring and administration interval adjustment accompanying the treatment with TNF inhibitors is the key to successful, individualized and targeted patient care. Concentrations of the TNF inhibitors adalimumab or infliximab can be specifically measured by serological assays. One possible cause of a decrease in drug efficacy is the generation of antibodies against adalimumab or infliximab and sensitive detection of these anti-drug antibodies is also possible. Monitoring drug levels may contribute to effective and successful therapeutic treatment strategy.
In autoimmune diseases, such as chronic inflammatory bowel diseases (Crohn’s disease, ulcerative colitis), rheumatic diseases (rheumatoid arthritis, spondyloarthrosis) and psoriasis, the individual’s immune response is directed against its own healthy cells and tissues. During the misdirected inflammatory response, macrophages produce and release the pro-inflammatory cytokines such as TNF, which induces fever, apoptotic cell death and inflammation. Treatment with TNF inhibitors interrupts the inflammatory response by neutralization of TNF activity. TNF inhibitors are biologics in form of monoclonal antibodies that bind mono specifically to TNF. Prominent representatives of monoclonal antibodies against TNF are infliximab (IFX) and adalimumab (ADL). IFX is a chimeric monoclonal antibody and acts as the active ingredient of Remicade®, which was the first drug from the group of TNF inhibitors to be approved for therapeutic use in 1998. ADL is an entirely human monoclonal antibody and is the active ingredient of Humira®. It was first approved in 2002 and can be administered subcutaneously by the patients themselves. As an economic alternative to the original prepar-ations, biosimilars are available for both drugs.
Therapeutic drug monitoring
Autoimmune diseases such as rheumatic diseases, chronic inflammatory bowel diseases and psoriasis cannot be cured. Instead, patients are treated symptomatically with antiinflammatory drugs, such as TNF inhibitors. However, the clinical reality shows that patients exhibit deviant responses to these biologics, as pharmacokinetics and pharmacodynamics differ from patient to patient and fluctuations occur in time. Pharmacokinetics includes the absorption, distribution, metabolism and excretion of the drug, whereas pharmacodynamics describes biochemical and physiological mechanisms of action and effects of a drug within the human body.
Therapeutic drug monitoring (TDM) can be used to manage and optimize drug administration based on measurement of drug concentration . TDM is beneficial if dosage of a drug shows high pharmacokinetic variability and has an optimal therapeutic dose which may show clear reduction of symptoms with some delay after start of treatment.