Therapeutic drug monitoring with biologic agents in immune mediated inflammatory diseases

ABSTRACT

Introduction: Biologic therapy has revolutionized the treatment of immune mediated inflammatory diseases (IMID), such as inflammatory bowel disease (IBD), rheumatoid and psoriatic arthritis, ankylosing spondylitis and psoriasis. Nevertheless, some patients exhibit primary nonresponse (PNR) or secondary loss of response (SLR) to biologics.

Areas covered: This collaborative review provides data on the role of therapeutic drug monitoring (TDM) in IMID for optimizing biologic therapy including infliximab, adalimumab, certolizumab pegol etanercept and golimumab vedolizumab, secukinumab and ustekinumab.

Expert opinion: Most exposure-response relationship studies show a positive correlation between biologic drug concentrations and favorable therapeutic outcomes in IMID with higher drug concentrations typically associated with more objective outcomes. Clinically, reactive TDM rationalizes the management of PNR and SLR to anti-tumor necrosis factor therapy and is emerging as the new standard of care in IBD as it is also more cost-effective than empiric dose escalation. Preliminary data suggest that proactive TDM with the goal to achieve a threshold drug concentration is associated with better therapeutic outcomes when compared to empiric drug optimization and/or reactive TDM of infliximab and adalimumab in IBD. However, more data from well-designed prospective studies are needed to prove the benefit of TDM-based algorithms in real life clinical practice in IMID.

KEYWORDS:

• Inflammatory bowel disease
• rheumatoid arthritis
• psoriasis
• biologic therapy
• immunogenicity
• therapeutic drug monitoring
• anti-TNF therapy
• secukinumab
• ustekinumab
• vedolizumab

Article highlights

• There is generally a positive correlation between drug concentrations and favorable therapeutic outcomes in immune mediated inflammatory diseases.

• Reactive therapeutic drug monitoring (TDM) has rationalized the management of patients with loss of response to biologics in in inflammatory bowel disease (IBD)and has been proven more cost-effective compared to empiric infliximab dose optimization.

• Preliminary data suggest that proactive TDM of anti-TNF therapy is associated with better therapeutic outcomes when compared to empiric dose optimization and/or reactive TDM in IBD.

• Proactive TDM of anti-TNF provides a more rational approach to determine in which patients de-escalation of therapy is possible.

• More studies are needed to clarify the role of proactive TDM for non-anti-TNF biologics in immune mediated inflammatory diseases.

• Despite the evidence between serum drug concentrations and clinical outcome, more studies, including cost-effectiveness analyses, are necessary to establish the usefulness of TDM as an intervention in rheumatology and dermatology.

Declaration of interest

AS Cheifetz has received consultancy fees from Janssen, Abbvie, Takeda, Pfizer, Samsung, Arena, Bacainn, EMD Serono, Arsanis, Grifols, Prometheus; and research support from Inform Diagnostics. J. Lambert has been an advisor/speaker for and received educational grants from AbbVie, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis, Pfizer, and UCB. G. Wolbing has received a research grant from Pfizer, and honoraria for lectures from Pfizer, UCB, AbbVie, Biogen and BMS. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

K Papamichail is supported by Ruth L. Kirschstein NRSA Institutional Research Training Grant T32 DK007760. The content of this project is solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health (NIH).