Statistics from Altmetric.com
Biological therapy has been introduced in the late nineties and has significantly improved outcome of many chronic inflammatory conditions such as rheumatoid arthritis, spondylarthritis, Crohn's disease and ulcerative colitis (UC), psoriasis and psoriatic arthritis. The loss of efficacy of biological therapy over time, however, has proved to be the Achilles heel of this treatment. Loss of response is in most cases due to neutralising antibodies and low trough levels. Other reasons for lower response rates theoretically include other immune pathways driving the inflammation or absence of residual lesions although no studies have systematically investigated the reasons for loss of response in a consecutive cohort of patients. Mainly in patients with symptoms but no signs of inflammation in the blood, new imaging is recommended to rule out other reasons for loss of response such as symptoms due to irritable bowel syndrome, bile salt malabsorption and/or underlying strictures.1 ,2
Loss of response due to immunogenicity is usually managed clinically by decreasing the interval between infusions or injections, by increasing the dose, by adding immunomodulatory agents (methotrexate, azathioprine) or by switching within the same class to more humanised or human antibodies. However, these therapeutic interventions are often done in vain, only leading to higher costs and a potential increasing risk for side effects. Thus, despite interventions, a significant proportion of patients still drop-out per year.3
A drug can only exert its full effect when the lowest level (ie, level measured just before the next scheduled administration of medicine (=also called trough level (TL))) is sufficiently high. Thus optimal use of the drug implies the correct dosage which also means that peak levels and average levels should not exceed concentrations which are associated with increased toxicity. Therapeutic drug monitoring (TDM) with measurements of TL at regular intervals is routinely carried out …
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.