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jakinhibitors

JAK inhibitors

Introduction

  • the JAK-family of cytokine receptors consists of four members: JAK1, JAK2, JAK3 and TYK2 that have different association patterns to receptors and are part of the Signal Transducer and Activation of Transcription (JAK-STAT) pathway
  • some JAK inhibitors are selective for specific JAK enzymes, which may influence their efficacy and safety profiles
    • JAK3 inhibitors necessarily cause a loss or total absence of T cells and natural killer cells while leaving a normal amount of B cells

Potential use cases

  • Rheumatoid arthritis
  • Psoriatic arthritis
  • Juvenile idiopathic arthritis
  • Axial spondyloarthritis
  • Ulcerative colitis
  • Atopic dermatitis
  • Alopecia areata

Potential side effects

  • increased risk of infections (like shingles) - hence live vaccinations soon before starting Rx or concurrently are NOT recommended
  • increased risk of major cardiovascular problems, such as heart attack and stroke, cancer, blood clots, serious infections and death, as compared with tumour necrosis factor (TNF) inhibitors1)
  • elevated cholesterol
  • blood clots
  • hypertension
  • anaemia
  • headache
  • diarrhoea
  • increased blood creatine phosphokinase
  • in some cases, increased risk of certain cancers, particularly in older adults with rheumatoid arthritis
  • increases risk of acne 2.5-fold more than when atopic dermatitis patients are Rx with Th2 cytokine inhibitors
  • others

General contra-indications include

  • active tuberculosis and other severe infections
  • recent live vaccination
  • severe liver impairment (Child–Pugh score C)
  • pregnancy
  • most are not approved for children aged under 12 yrs
  • should generally be avoided in:
    • age 65 or over
    • those at increased risk of cardiovascular problems such as heart attacks or stroke (eg. including current or past long-time smokers)
    • those at increased risk of cancer
    • those with risk factors for DVT / PE
    • those who have not yet had zoster vaccination (should be done well before starting Rx)

JAK-STAT system inhibitors

pan-JAK inhibitors

  • baricitinib (Olumiant)
    • oral agent mainly used to Rx rheumatoid arthritis and is a disease-modifying antirheumatic drug (DMARD)
  • delgocitinib (Corectim)
    • treatment of atopic dermatitis
    • FDA in 2025 approved topical treatment of adults with moderate to severe chronic hand eczema

JAK 1 selective inhibitors

  • ivarmacitinib
  • upadacitinib (Rinvoq)
    • used for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis
  • tofacitinib (Xeljanz)
jakinhibitors.txt · Last modified: 2026/01/28 09:46 by gary1

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