Medication Class Introduction

Janus kinase (JAK) inhibitors were first introduced in the 2010s.1,2 They are a class of targeted synthetic small molecules that target Janus kinases (JAKs) and inhibit their interaction with Signal Transducer and Activator of Transcription (STAT) proteins, thereby interrupting the JAK-STAT signaling pathway.2–5 This pathway is involved in the inflammatory processes associated with inflammatory bowel disease (IBD).2,3,5,6

Targeted synthetic small molecule therapies are low-molecular-weight compounds that diffuse through cell membranes.3,4 Unlike biological therapies such as monoclonal antibodies, which are large proteins usually administered by injection, targeted synthetic small molecules are typically administered orally and have a low risk of provoking immunogenicity.3

IBD Treatment Landscape3,7–16

IBD treatment landscape

JAK=Janus kinase; S1P=sphingosine-1-phosphate; TNF=tumor necrosis factor.

Role in IBD Pathogenesis

In IBD, binding of a proinflammatory cytokine to its receptor promotes receptor pairing and activation of JAKs through addition of a phosphate group, known as phosphorylation.2,3,5,6,17 JAKs are enzymatic proteins that, once activated, phosphorylate and activate STATs. Activated STATs form dimers, or pairs, and translocate to the cell nucleus, where they regulate transcription of immune and inflammatory genes, leading to the production of inflammatory mediators.

JAK role in IBD pathogenesis

DNA=deoxyribonucleic acid; JAK=Janus kinase; P=phosphate group; STAT=Signal Transducer and Activator of Transcription.

Mechanism of Action in IBD

JAK inhibitors are targeted synthetic small molecules that can diffuse through the cell membranes of immune cells and bind to sites located on JAKs.2,3,6 This binding blocks the phosphorylation and activation of JAKs and subsequently STATs, thereby disrupting intracellular signaling and downstream transcription of genes involved in the production of inflammatory mediators.2,3,5,6

JAK inhibitors mechanism of Action in IBD

DNA=deoxyribonucleic acid; JAK=Janus kinase; P=phosphate group; STAT=Signal Transducer and Activator of Transcription.

Resources

Current IBD Treatment Guidelines

Guidelines for managing IBD are available from the American College of Gastroenterology (ACG) and the American Gastroenterological Association (AGA). You can access them through the following links:

Resources to Help Explain Medication Options for IBD to Patients

The Crohn’s & Colitis Foundation resources below may help you explain medication options, including the mechanism of action of IBD medication classes and how they are designed to work in the body, to your patients with IBD.

Resources to Help Understand Medical Management of IBD From UpToDate®

The UpToDate® resources below may help you understand medical management of IBD in adults including but not limited to disease activity, severity, and risk, as well as medication options for induction and maintenance.

For More Information on IBD Medications

To learn more about the medications commonly used to treat IBD—including potential side effects and safety considerations—please refer to the following resource:

Links to third-party websites are provided as resources and not intended to be an endorsement. Takeda is not responsible for their content.

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