Is there a role for therapeutic sphingolipids in inflammatory bowel disease?

ABSTRACT

Introduction

Inflammatory bowel diseases (IBD), which include Crohn’s disease and ulcerative colitis, are lifetime chronic inflammatory disorders. Over the past few decades, new therapeutic approaches, including early and more effective intervention with immunomodulators and biological agents, increased the possibility of a favorable modification of the natural history of IBD. Despite this progress, there is still a need to explore new therapeutic options.

Area covered

Here, we review the literature about the role of therapeutic sphingolipids in inflammatory bowel disease patients.

Expert opinion

Despite the great increase of treatment options in the last 20 years, many patients still do not respond to the induction therapy (primary non-responders) or lose response over time (secondary responders). Small-molecule drugs are a promising group of drugs with low molecular weight, an oral route of administration, and low immunogenicity offering several advantages when compared to biologics such as anti-TNFs and anti-integrins. Sphingosine-1-phosphate (S1P) receptor modulators are some among the new small molecules currently under clinical investigation for the treatment of IBD.

KEYWORDS:

• Ulcerative colitis
• Crohn’s disease
• inflammatory bowel disease
• leukocytes
• sphingosine-1-phosphate
• small molecules
• inflammation
• trafficking

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Correction

Article highlights

• Blockade of lymphocyte recirculation in lymph nodes can be targeted through modulation of sphingosine 1-phosphate (S1P) receptors

• Sphingolipids are orally administered, stable, and non-immunogenic drugs with a shorter half-life.

• Ozanimod could be a promising new therapeutic option for both UC and CD

• Etrasimod showed encouraging results in UC

• In CD, amiselimod did not show any benefit compared to placebo

• Clinical data on S1P modulators is promising although still insufficient to draw conclusions on real efficacy

• In the coming months, a wealth of new data is expected to be published

Declaration of interest

M Argollo has served as speaker, consultant, and member of the advisory board for Abbvie, Janssen, Takeda, and Pfizer.

D Gilardi has served as speaker, consultant, and member of the advisory board for Nikkiso GmBH, Sofar Spa, Biofer Spa, J&J, Pfizer, Takeda, and Roche.

S Danese has served as speaker, consultant, and advisory board member for Schering-Plough, AbbVie, MSD, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Aphawasserman, Genetech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, J&J, Nikkiso Europe GmBH, Theravance.

L Peyrin-Biroulet received consulting fees from Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Pharmacosmos, BMS, UCB- pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, Pfizer, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, and lecture fees from Merck, Abbvie, Takeda, Janssen, Ferring, Norgine, Tillots, Vifor, Mitsubishi, and HAC- 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.

Reviewer Disclosures

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

Additional information

Funding

This paper was not funded.