Will novel oral formulations change the management of inflammatory bowel disease?

ABSTRACT

Introduction: The traditional management of inflammatory bowel disease (IBD) with sulphasalazine/5-aminosalicylic acid, glucocorticoids and immunomodulators (i.e., thiopurines and methotrexate) was nearly two decades ago extended with intravenously or subcutaneously administered biologics (i.e., tumor necrosis factor inhibitors and later gut-selective integrin antagonists). However, recently, orally administered treatments with simple, well-characterized, and stable structures consisting of either small molecules or anti-sense therapy have been devised.

Areas covered: This review discusses the current approaches with promising new oral drugs with distinct modes of action, including: the Janus kinase inhibitors (i.e., tofacitinib, filgotinib and peficitinib); the immunomodulatory drug (laquinimod); a small α4 antagonist (AJM300); agonists for sphingosine-phosphate receptors (i.e., ozanimod, APD334, and amiselimod), as well as anti-sense therapy (mongersen) targeting SMAD7, drugs which directly target intracellular pathways of relevance for intestinal inflammation.

Expert opinion: A new avenue using easily administered oral therapies for the management of IBD is being introduced. While their place in the clinical armamentarium remains to be proven, it is likely that many of these drugs will find their place in the treatment algorithm of IBD in the next few years. Thus, we will face times in which IBD therapy will be based on significantly more tablets than prescribed today.

KEYWORDS:

• Anti-sense therapy
• Crohn’s disease
• inflammatory bowel disease
• oral therapy
• small molecules
• ulcerative colitis

Article highlights

• Novel orally developed therapeutics are under clinical investigation for inflammatory bowel disease.

• These drugs are small molecules or anti-sense therapies.

• These drugs have the advantage compared with biologics that they are easily administered (oral), have stable structures, are non-immunogenic, have shorter half-life, are not associated with hidden costs for intravenous management, and have lower manufacturing costs.

• The group of drugs consists of JAK inhibitors, α4 antagonists, sphingosine-1-phosphate receptor modulators as well as SMAD7 anti-sense oligonucleotides.

• Based on the pathophysiological role of TGF-β1 in IBD concerns exist that influencing TGF-β1 with SMAD7 anti-sense therapy may accelerate fistula formation, fibrosis and possibly stenosis when used as maintenance therapy.

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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.