Clinical impact of immunomonitoring in the treatment of inflammatory bowel disease

Abstract

Despite improvement in outcomes, loss of response (LOR) to tumor necrosis factor-alpha (TNFα) therapies is a big concern in the management of inflammatory bowel disease. LOR is associated with flares of disease, increased hospitalisation rates, need for surgical interventions, and decline in quality of life. LOR may be multifactorial, but immunogenicity makes a significant contribution. Traditionally doses of anti-TNFα have been adjusted based on clinical response, using a standard approach. Immunomonitoring involves the measurement of anti-TNFα trough and antibody levels. It takes into account the underlying pharmacokinetics of anti-TNFα therapies. Expanding on this a treat to target approach may be used, where doses are intensified, or tailored to the individual based on the measurement of anti-TNFα trough and antibody levels. This review looks at the history, evolution, and clinical impact that immunomonitoring is having in the treatment of inflammatory bowel disease. It will focus on the role of immunomonitoring in helping to achieve long lasting deep remission and mucosal healing. It will explore the different options in terms of best measuring trough and antibody levels, explore possible advantages of immunomonitoring, and discuss its role in best optimising response, at induction, during the maintenance phase of treatment, as well as a role in withdrawing or switching therapy.

Clinical Relevance of Anti-TNF Antibody Trough Levels and Anti-Drug Antibodies in Treating Inflammatory Bowel Disease Patients

“…However, no official recommendation exists about the optimal range of TL to maintain clinical remission. In addition, the consequences of TL measurements, including dosing or time interval adaptation of the biological, change of the biological, and addition or alterations of immunomodulatory treatments, have only been described in a few studies [15-17].…”

A case of intestinal Behcet’s disease under Adalimumab

“…[11] Current evidence suggests that there may be clinical benefit to monitoring of drug troughs and antibody levels during treatment with TNFα inhibitors. [10] Whether infliximab at high-dose is more effective than adalimumab at regular dose, as suggested by our case, remains unclear. Increasing the dose of infliximab has previously shown to be efficacious in inducing remission of intestinal BD.…”

“…The mechanism of loss of response to TNFα inhibitors is thought to be secondary to the formation of antibodies to the medication, which leads to either blocking of the drug activity or faster drug clearance as evidenced by lower drug trough levels. [10] In patients treated with Infliximab for inflammatory bowel diseases, antibodies against the medication form in a significant proportion of patients with nearly 30% requiring adjustments to their treatment. [11] Current evidence suggests that there may be clinical benefit to monitoring of drug troughs and antibody levels during treatment with TNFα inhibitors.…”

New steps in infliximab therapeutic drug monitoring in patients with inflammatory bowel diseases

“…Despite improvement in clinical outcome, loss of response to anti‐TNF‐α Mabs remains a major concern in the management of IBD patients. Increasing evidences suggested that therapeutic drug monitoring (TDM) of anti‐TNF‐α Mabs could help to improve remission rate or mucosal healing achievement but the clinical interest of TDM of anti‐TNFα Mabs in IBD patients remains to be further demonstrated . One of the limitations lies in the absence of standardization of the analytical methods used to measure IFX plasma concentration.…”

“…One of the limitations lies in the absence of standardization of the analytical methods used to measure IFX plasma concentration. Indeed, up to now, all previous studies used enzyme‐linked immunosorbent assay (ELISA) or homogeneous mobility shift assay, but the systematic bias and lack of specificity of some ELISA methods could be of major concerns, and lead to the determination of different clinically relevant IFX thresholds or different therapeutic strategies .…”