Efficacious dosing regimens for anti-TNF therapies in inflammatory bowel disease: where do we stand?

ABSTRACT

Introduction

During the last decades, biologics have revolutionized the treatment of Crohn’s disease and ulcerative colitis. Even though the inflammatory bowel disease (IBD) armamentarium is rapidly expanding with novel biologics, anti-tumor necrosis factor (TNF) antibodies remain the first-line biologic therapy in most areas of the world. However, anti-TNF therapy is not effective in all patients (primary non-response) and patients can lose effect over time (secondary loss of response).

Areas covered

This review provides an overview of the current induction and maintenance dosing regimens of the available anti-TNF antibodies and associated challenges in adult patients with IBD. We outline different strategies to overcome these difficulties, including combination therapy, therapeutic drug monitoring (TDM), and dose escalation. Finally, we discuss expected future progress in anti-TNF management.

Expert opinion

Anti-TNF agents will remain a cornerstone of IBD treatment in the coming decade. Progress will be made in biomarkers for the prediction of response and individualized dosing regimens. The advent of subcutaneous infliximab challenges the need for concomitant immunosuppression.

KEYWORDS:

• Anti-drug antibody
• Anti-TNF
• dosing regimens
• immunogenicity
• inflammatory bowel disease
• personalized medicine
• therapeutic drug monitoring
• trough level

Article highlights

• Challenges of anti-TNF therapies include primary non-response, secondary loss of response, and drug toxicity.

• Higher anti-TNF serum concentrations have been associated with superior outcomes in IBD patients upon induction and maintenance therapy.

• Possible strategies in patients with non-response or loss of response to anti-TNF therapy are dose escalation, therapeutic drug monitoring, and optimization of combined immunomodulatory therapy.

• With increasing evidence of the effectiveness of therapeutic drug monitoring, proactive and reactive serum drug measurements are widely used in clinical practice as tools to optimize anti-TNF dosing.

• Clinical trials of subcutaneous infliximab and the use of therapeutic drug monitoring in the induction phase are ongoing and may guide physicians to optimize dosing regimens of anti-TNF therapies in patients with inflammatory bowel disease.

Declaration of interest

G D’Haens has received consultancy and/or speakers’ fees from AbbVie, Alimentiv BV, Boehringer Ingelheim, Celltrion, Galapagos, Gossamer Bio, GSK, Janssen, Eli Lilly, Pfizer, Progenity, Prometheus Biosciences, Takeda, Tillotts, Ventyx; research grants from Pfizer, Takeda, Eli Lilly. 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

A reviewer on this manuscript has disclosed that they are a consultant for Takeda, Pfizer, Arena, and Bristol Myers Squibb. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.