III. Contraindications

IV. Mechanism

  1. Janus Kinase (JAK) and the JAK/STAT Pathway
    1. Janus Kinase (JAK) is a family of intracellular Tyrosine Kinases that trigger a signaling cascade of Cytokines
    2. JAK acts on STAT transcription factors, triggering gene transcription related to inflammation
    3. Janus Kinase (JAK) is named for its Protein's 2 phosphate-Transferring domains
  2. Janus Kinase Inhibitor
    1. JAK Inhibitors are small molecule agents that interfere with Cytokine signalling by blocking their receptor binding

V. Medications

  1. Ruxolitinib or Jakafi (JAK1 and JAK2 Inhibitor)
    1. Indicated in Rheumatoid Arthritis and Myelofibrosis (including Polycythemia Vera)
  2. Baricitinib or Olumiant (JAK1 and JAK2 inhibitor)
    1. Indicated in Rheumatoid Arthritis and Alopecia Areata
  3. Upadacitinib or Rinvoq (JAK1 inhibitor)
    1. Indicated in Rheumatoid Arthritis
  4. Tofacitinib or Xeljanz (JAK3 Inhibitor)
    1. Indicated in Rheumatoid Arthritis and Psoriatic Arthritis

VI. Adverse Effects

  1. Venous Thromboembolism
  2. Sudden cardiovascular death (associated with Tofacitinib)
    1. FDA black box warning for major cardiovascular event risk
  3. Immunosuppression
    1. Tuberculosis reactivation risk (test for Latent Tb before starting)
    2. Increased risk of opportunistic infection (e.g. invasive fungal infections, Pneumonia, Shingles)
    3. Malignancy risk (e.g. Lymphoma)

VII. Drug Interactions

  1. Live Vaccines
    1. Hold JAK Inhibitors for 1 week before and 4 weeks after Live Vaccines

VIII. References

  1. (2019) Presc Lett 26(10): 58

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Ontology: ruxolitinib (C2931926)

Definition (NCI) An orally bioavailable Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities. Ruxolitinib pecifically binds to and inhibits protein tyrosine kinases JAK 1 and 2, which may lead to a reduction in inflammation and an inhibition of cellular proliferation. The JAK-STAT (signal transducer and activator of transcription) pathway plays a key role in the signaling of many cytokines and growth factors and is involved in cellular proliferation, growth, hematopoiesis, and the immune response; JAK kinases may be upregulated in inflammatory diseases, myeloproliferative disorders, and various malignancies.
Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C540383
SnomedCT 702806008, 703779004
English INCB18424, ruxolitinib, RUXOLITINIB, (3R)-3-cyclopentyl-3-(4-(7h-pyrrolo(2,3-d)pyrimidin-4-yl)pyrazol-1-yl)propanenitrile, INCB-18424, Oral JAK Inhibitor INCB18424, chemotherapeutics growth-signaling inhibitors ruxolitinib, chemotherapeutics growth-signaling inhibitors ruxolitinib (medication), Ruxolitinib (substance), Ruxolitinib, Ruxolitinib (product)