Profile of Tofacitinib in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Recent Data

Drug Des Devel Ther. 2019 Dec 2:13:4091-4105. doi: 10.2147/DDDT.S182891. eCollection 2019.

Abstract

Recent advances in the understanding of the pathophysiology of ulcerative colitis (UC) have led to the expansion of our therapeutic arsenal. Conventional treatment options, including aminosalicylates, corticosteroids, thiopurines, and calcineurin inhibitors, fail to control the disease in a significant proportion of patients. Approximately 25-50% of the patients treated with tumor necrosis factor antibodies (anti-TNFα) are primary and secondary non-responders to therapy. Tofacitinib is a novel orally administered small synthetic molecule that inhibits a homologous family of enzymes, termed Janus kinases that modulate multiple key cytokines involved in the pathogenesis of UC. Phase II and III trials showed promising results in UC, leading the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to approve its administration for the induction and maintenance of remission in moderate-to-severe UC. Herein, we review tofacitinib for the management of UC, its mechanism of action pharmacokinetic properties, efficacy, and safety.

Keywords: Jakinibs; Janus kinase inhibitors; tofacitinib; ulcerative colitis.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Colitis, Ulcerative / drug therapy*
  • Humans
  • Piperidines / administration & dosage
  • Piperidines / pharmacokinetics
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / therapeutic use*
  • Pyrroles / administration & dosage
  • Pyrroles / pharmacokinetics
  • Pyrroles / therapeutic use*

Substances

  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • tofacitinib