JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis

Rheumatology (Oxford). 2019 Feb 1;58(Suppl 1):i43-i54. doi: 10.1093/rheumatology/key276.


Janus kinase (JAK)/signal transducers and activators of transcription (STATs) are a group of molecules associated with one of the major pathways through which many cytokines exert and integrate their function, and as such they are increasingly recognized as playing critical role in the pathogenesis subserving various immune-mediated diseases, including RA, PsA, SpAs, IBD, skin disorders (e.g. alopecia areata, atopic dermatitis), single-gene disorders like interferonopathies, and others. JAKs are the key initiating players of the JAK/STAT pathway. Upon binding of their respective effector molecules (cytokines, IFNs, growth factors and others) to type I and type II receptors, JAKs are activated, and through phosphorylation of themselves and of other molecules (including STATs), they mediate signal transduction to the nucleus. A class of drugs-called JAK inhibitors or JAKinibs-that block one or more JAKs has been developed in the last decade, and now numbers >20 members. Although, so far, JAK inhibitors have been marketed only for RA and PsA, these drugs have been tested in phase 2 and phase 3 clinical trials for other inflammatory conditions and beyond. In this review, we summarize the clinical data, including efficacy and safety, available for JAK inhibitors used in some immune-mediated conditions other than RA.

Keywords: JAK inhibitors; JAK/STAT pathway; immune-mediated diseases.

Publication types

  • Review

MeSH terms

  • Alopecia Areata / drug therapy
  • Aortic Diseases / drug therapy
  • Arthritis, Psoriatic / drug therapy*
  • Arthritis, Rheumatoid / drug therapy
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases of the Nervous System / drug therapy
  • Chilblains / drug therapy
  • Cytokines
  • Dental Enamel Hypoplasia / drug therapy
  • Dermatitis, Atopic / drug therapy
  • Giant Cell Arteritis / drug therapy
  • Humans
  • Immunologic Deficiency Syndromes
  • Inflammatory Bowel Diseases / drug therapy*
  • Janus Kinase Inhibitors / therapeutic use*
  • Lupus Erythematosus, Cutaneous / drug therapy
  • Metacarpus / abnormalities
  • Muscular Diseases / drug therapy
  • Nervous System Malformations / drug therapy
  • Odontodysplasia / drug therapy
  • Osteoporosis / drug therapy
  • Psoriasis / drug therapy
  • Spondylarthropathies / drug therapy*
  • Uveitis / drug therapy
  • Vascular Calcification / drug therapy


  • Cytokines
  • Janus Kinase Inhibitors

Supplementary concepts

  • Aicardi-Goutieres syndrome
  • Chilblain lupus 1
  • Singleton Merten syndrome
  • chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature