Advancing therapeutic frontiers: a pipeline of novel drugs for luminal and perianal Crohn's disease management

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Crohn's disease (CD) is a chronic, complex inflammatory disorder of the gastrointestinal tract that presents significant therapeutic challenges. Despite the availability of a wide range of treatments, many patients experience primary non-response, secondary loss of response, or adverse events, limiting the overall effectiveness of current therapies. Clinical trials often report response rates below 60%, partly due to stringent inclusion criteria. Emerging therapies that target novel pathways offer promise in overcoming these limitations. This review explores the latest investigational drugs in phases I, II, and III clinical trials for treating both luminal and perianal CD. We highlight promising therapies that target known mechanisms, including selective Janus kinase inhibitors, anti-adhesion molecules, tumor necrosis factor inhibitors, and IL-23 selective inhibitors. In addition, we delve into novel therapeutic strategies such as sphingosine-1-phosphate receptor modulators, miR-124 upregulators, anti-fractalkine (CX3CL1), anti-TL1A, peroxisome proliferator-activated receptor gamma agonists, TGFBRI/ALK5 inhibitors, anti-CCR9 agents, and other innovative small molecules, as well as combination therapies. These emerging approaches, by addressing new pathways and mechanisms of action, have the potential to surpass the limitations of existing treatments and significantly improve CD

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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