Primary non-response in inflammatory bowel disease, definition, potential causes, therapeutic drug monitoring and microbiota – a review

Tumor necrosis factors (TNF-α) are pro-inflammatory cytokines centrally involved in autoimmunity. Monoclonal antibodies against TNF-α are used to treat several autoimmune diseases including inflammatory bowel disease (IBD). The proportion of patients who experience primary non-response (PNR) to anti-TNF treatment is approximately 13–40%. Secondary loss of response (LOR) to anti-TNF agents happens in 23–46% of IBD patients leading to a drug discontinuation rate of 5–13%. A combination of factors including disease characteristics (e.g., phenotype, location, and severity), drug response (e.g., pharmacokinetics, pharmacodynamics, or immunogenicity), and treatment strategy (e.g., dosing regimen) has been associated with PNR and LOR. Therapeutic drug monitoring (TDM) relies on the measurement of serum concentrations of anti-TNF agents and anti-drug antibodies. TDM can be utilized to identify PNR and LOR and to assist clinicians in their decision-making. Additionally, TDM is used to optimize drug therapy (e.g., dose escalation) for patients who exhibit LOR. Recently, gut microbiota was believed to play a central role in immune regulation, and influence response to TNF-α antagonists. Microbial diversity for certain taxa can become a prognosis factor to monitor the response to treatment. In this article, we aim to review PNR and LOR, and discuss microbiota profiles associated with their occurrence.