Ustekinumab is a human therapeutic Monoclonal Antibody that targets Interleukin-12 and Interleukin-23.
In Inflammatory Bowel Disease (IBD) and other immunological disorders such as Rheumatoid Arthritis (RA) and Psoriasis, the use of MAb therapy requires a personalised approach. The long term effectiveness of Interleukin-12 and Interleukin-23 agents such as Ustekinumab may be strongly influenced by its bioavailability, pharmacokinetics and immunogenicity.
Clinical trials have shown that over time a high proportion of patients may lose response to biological treatments. In recognition of this phenomenon and in an attempt to better understand the course of disease there has been an increase in the use of therapeutic drug monitoring. Measuring serum trough drug levels to ensure an adequate drug concentration is maintained within a defined 'therapeutic window' is important for achieving clinical remission.
Failure to respond to biological treatments during the induction phase, or losing response during the maintenance phase, can be attributed to immunogenicity. Anti-Interleukin-12 and anti-Interleukin-23 blockers (e.g. Ustekinumab) may trigger immunogenic responses in individuals which can reduce the serum concentration of available drug thus altering its effectiveness.
Anti-Drug-Antibodies (ADA), impede drug activity and may cause severe allergic reactions too and so concomitant use of immunosuppressants to reduce antibody formation is common, but it is not always indicated.
Anti-drug antibodies can also be measured in serum to help provide a more complete clinical picture as to why a patient may have lost control of their disease. A combination of therapeutic drug and anti-drug antibody monitoring provides a potential to preempt the course of disease, predict disease outcome, and to personalise a treatment strategy.
In IBD management, studies have shown that therapeutic drug monitoring strategies for infliximab and adalimumab are cost effective and significantly change the clinical decision-making when managing the disease. Similar strategies for Ustekinumab may deliver similar beneficial results.