Therapeutic drug monitoring to improve outcome of anti-TNF drugs in pediatric inflammatory bowel disease

ABSTRACT

Introduction: Medical treatment of pediatric inflammatory bowel diseases (IBD) has been greatly changed by the introduction of a number of biologic agents that are able to target various players of the immune response. In particular, monoclonal antibodies against the pro-inflammatory cytokine TNF-alpha (TNF) such as infliximab, adalimumab, and golimumab are now in the clinics both in induction and maintenance therapy, and several efforts are currently ongoing to optimize the use of these drugs in children.

Areas covered: This review focuses on therapeutic drug monitoring (TDM) of anti-TNF levels and antidrug antibodies (ADAs), in IBD children. A revision of the analytical assays used for assessing anti-TNF plasma levels is also provided.

Expert opinion: Although there is a consensus across studies that higher anti-TNF trough levels are associated with a better clinical outcome, and that early anti-TNF serum measurements could be predictive of long-term response, it is still not clear what the best predictive time of sampling is and what the ideal target drug plasma concentration to achieve. Indeed, there are a number of published studies, particularly in pediatric cohorts, limited by the population size analyzed and more prospective large studies are needed to examine the value of these predictive markers.

KEYWORDS:

• Anti-TNF drugs
• biologics
• children
• Crohn’s disease
• inflammatory bowel disease
• therapeutic drug monitoring
• ulcerative colitis

Article highlights

• IBD is common in the pediatric age. Clinical features are similar between children and adults but pediatric onset disease is often characterized by a particularly aggressive course and unique complications, such as growth failure and delayed puberty.

• Anti-TNF agents are now routinely used in pediatric IBD, both in induction and in maintenance therapy. However, their use is limited by primary and secondary failures, by the incidence of adverse effects and by elevated costs. TDM, meant as evaluation of anti-TNF trough levels and antidrug antibodies, could help physicians in overcoming these limits and optimizing drug management.

• Trough levels play the best role as predictors of clinical outcome. It is still an open question what are the ideal predictive sample timing and therapeutic range to achieve.

• Anti drug antibodies are generally investigated in case of loss of therapeutic response and are eventually used to guide patients to alternative anti-TNF agents.

• Several reliable analytical assays are now available. They present different advantages and disadvantages, and are chosen according to medical needs..

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was funded by Italian Ministry of Health; IRCCS Burlo Garofolo, RC 1/17