Anti-TNF-α therapies for the treatment of Crohn’s disease: the past, present and future

ABSTRACT

Introduction: Anti-TNF-α therapy is a novel approach that has transformed the way moderate-to-severe Crohn’s disease (CD) is treated and has significantly improved clinical outcomes of patients with enhanced remission induction and maintenance efficacies. As a result, anti-TNF-α agents have become the primary cost driver in the treatment of CD, as the frequency of hospitalizations and surgical interventions have been drastically reduced.

Areas Covered: In the review, the authors cover current anti-TNF-α treatments for CD including efficacy, mechanisms of action, pharmacokinetics and safety. In addition, the authors discuss future anti-TNF-α agents currently in the development pipeline including biosimilars, golimumab, oral AVX-470, TNF-α-kinoid vaccine, and non-biologic HMPL-004.

Expert opinion: While new therapeutics are in the pipeline like anti-integrin and anti-interleukin therapeutics, anti-TNF-α therapy remains at the forefront of CD treatment due to its long-term efficacy and safety profiles. The next horizon for new anti-TNF-α agents is biosimilars, which offer comparable safety and effectiveness to the originator molecules. Biosimilars promise to expand accessibility to anti-TNF-α therapy while significantly reducing the cost burden to patients and healthcare systems.

KEYWORDS:

• Anti-TNF
• golimumab
• AVX-470
• TNF-kinoid
• HMPL-004
• biologic
• Crohn’s disease
• Crohns
• biosimilar

Declaration of interest

The authors are supported by the UCLA Division of Digestive Diseases Center for Inflammatory Bowel Diseases. DW Hommes declares associations with AbbVie, AstraZeneca, Bristol-Myers Squibb, Cellerix, Centocor, Chemocentryx, ELAN, Falk, Ferring Pharmaceuticals, Genentech, Giuliani Pharma, Janssen Pharmaceuticals, Johnson & Johnson, Leo Pharma, Merck Serono, Merck Sharp and Doehme, NovImmune, Otsuka Pharmaceutical Co., Ltd, PDL BioPharma, Philips, Proctor & Gamble, Roche, Schering-Plough and UCB Pharma.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.

Article Highlights

• Infliximab, adalimumab, and certolizumab pegol are the most widely used anti-TNF-α monoclonal antibodies to treat Crohn’s disease and have demonstrated robust clinical efficacies.

• Over the past decade, multiple mechanisms of action of anti-TNF-α agents have been elucidated including neutralization, reverse signaling, apoptosis, and cytotoxicity with the exception of certolizumab pegol which neither induces apoptosis nor cytotoxicity due to the absence of a Fc antibody fragment in its structure.

• The most common safety concerns include injection site/infusion reactions, immunogenicity, and loss of response. While the most serious safety concerns are opportunistic infections, melanoma, and increased malignancy rates with concomitant immunomodulator use.

• Biologic use is the primary cost driver in the treatment of Crohn’s disease.

• CT-P13 is an infliximab biosimilar (generic biologic) approved in Europe with a similar efficacy and safety profile to the originator molecule and has a significantly lower cost than brand name infliximab.

• In addition to biosimilars, future anti-TNF-α treatments include golimumab, oral AVX-470, TNF-α-kinoid vaccine, and nonbiologic HMPL-004 extract.

This box summarizes key points contained in the article.