title: JAK inhibition for the treatment of rheumatoid arthritis: a new era in oral DMARD therapy.
abstract: BACKGROUND
  In rheumatoid arthritis (RA) there is a significant medical need for safe and effective oral disease-modifying anti-rheumatic drugs (DMARDs) for patients who respond inadequately to methotrexate, the first-line therapy in RA. Oral agents targeting Janus-associated kinases (JAKs) are the most promising new agents in clinical development. This review describes the preclinical and clinical activities of the most advanced JAK inhibitors with different JAK selectivity profiles.
  
  
  METHODS
  This review first describes the current treatment landscape and the pathophysiology of RA. Role for cytokines in the disease pathogenesis followed by significance of JAK/STAT pathway in cytokine signaling are discussed. Available chemical description and enzymatic data on the most advanced JAK inhibitors in clinical development are provided. Preclinical and clinical results that are publicly available are summarized. Review of literature was conducted using National Library of Medicine (NLM) database, 'PubMed'. In addition, all publicly disclosed data from companies that are developing the JAK inhibitors was researched to obtain the most up-to-date information of the compounds discussed in this report.
  
  
  CONCLUSIONS
  Emerging clinical results demonstrate that JAK inhibition is a validated new mechanism for the development of oral DMARD agents that is likely to join the armamentarium against RA in the near future.
authors.affiliation: Incyte Corp., Pharmacology & Toxicology, Experimental Station, Wilmignton, DE 19880, USA. kvaddi@incyte.com
authors.forename: Kris
authors.initials: K
authors.lastname: Vaddi
authors.forename: Monica
authors.initials: M
authors.lastname: Luchi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D004791:Enzyme Inhibitors; D050791:STAT Transcription Factors; D053612:Janus Kinases