Janus Kinase Inhibitor

Aka: Janus Kinase Inhibitor, JAK Inhibitor, Ruxolitinib, Jakafi

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II. Indications

  1. Rheumatoid Arthritis
  2. Psoriatic Arthritis
  3. Ulcerative Colitis
  4. Polycythemia Vera

III. Contraindications

  1. Live Vaccines (see Drug Interactions below)

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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