There is an ongoing, unmet need for effective therapies for Crohn’s disease. Treatments for Crohn’s disease continue to evolve from the traditional biologics to novel small molecules, with targeted mechanisms directed toward pathways that are dysregulated in Crohn’s disease. There are multiple emerging mechanisms of action, including Janus kinase inhibition, Smad7 inhibition, and sphingosine-1-phosphate receptor modulators, that are administered as oral medications, and small molecules represent the next generation of therapies for Crohn’s disease.
Key points
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Small molecule therapies for Crohn’s disease offer potential benefits over biologics, including shorter half-lives, lack of immunogenicity, and oral route of administration.
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Janus kinase inhibitors block multiple cytokine pathways simultaneously and will likely be an effective oral therapy for Crohn’s disease and ulcerative colitis.
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Filgotinib, a Janus kinase 1-specific inhibitor, was recently shown to be effective in inducing clinical remission in Crohn’s disease.
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Mongersen inhibits Smad7 and thereby restores transforming growth factor-β signaling and may be an effective oral targeted therapy.
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Sphingosine-1 phosphate receptor modulators impair B-cell and T-cell lymphocyte trafficking by downregulating receptors that facilitate egress from lymph nodes.
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