title: A pharmacokinetic and clinical assessment of tofacitinib for the treatment of rheumatoid arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is a chronic painful and debilitating autoimmune disease. Although the outcome for patients with RA has improved markedly in the past decades, driven largely by the advent of biological disease-modifying antirheumatic drugs (DMARDs) and updated management strategies, adequate disease control cannot be achieved in a substantial proportion of patients. Since RA is a syndrome with different biological subsets, DMARDs, with a novel mechanism of action, may represent a valuable addition to the current armamentarium. Tofacitinib is a novel synthetic DMARD that selectively inhibits Janus kinases (JAKs), particularly JAK1 and JAK3.
  
  
  METHODS
  This review describes the pharmacokinetics of tofacitinib. Furthermore, the article summarizes and comments the drug's efficacy and safety profile in RA patients. The authors furthermore assess data derived from the FDA's RA development program.
  
  
  CONCLUSIONS
  Tofacitinib is an oral synthetic DMARD displaying linear pharmacokinetics. Metabolism, primarily mediated by CYP3A4, accounts for 70% of the total clearance of the drug; the remaining 30% are renally excreted. Tofacitinib monotherapy, or in combination with traditional DMARDs, has demonstrated its efficacy while having an acceptable safety profile in RA patients who have responded inadequately to current DMARDs, including TNF antagonists. In view of its undetermined benefit to risk ratio, in the real-world population, tofacitinib should, for now, only be prescribed to selected patients.
authors.affiliation: University Hospital of Bordeaux, Hopital Pellegrin, Rheumatology, Place Amelie Raba-Leon, Bordeaux 33076, France. bernard.bannwarth@u-bordeaux2.fr
authors.forename: Bernard
authors.initials: B
authors.lastname: Bannwarth
authors.forename: Marie
authors.initials: M
authors.lastname: Kostine
authors.forename: Nicolas
authors.initials: N
authors.lastname: Poursac
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D053613:Janus Kinase 1; D053616:Janus Kinase 3