NICE guidance - Tofacitinib for moderately to severely active ulcerative colitis

NICE guidance states (1):

• Tofacitinib is recommended, within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults when conventional therapy or a biological agent cannot be tolerated or the disease has responded inadequately or lost response to treatment

Tofacitinib (1,2,3):

• Janus kinases (JAKs) are a group of four intracellular tyrosine kinases mediating the signal transduction of multiple cytokines implicated in several functions including the activation of inflammation
  • JAKS have pivotal role in sustaining chronic inflammation, by stimulating the activity of T and B cells, and the production of mucus and antibodies
  • tofacitinib
    • is an oral small molecule pan-Janus kinase (JAK) inhibitor (molecular weight 312.4 Da; 504.5 for the citrate salt)
    • is the first oral formulation for the treatment of UC (ulcerative colitis)
    • acts on a multitude of cytokines at the same time by inhibiting the JAK/ctivator of transcription (STAT) pathway, resulting in a wider effect on the gastrointestinal inflammation
    • blocks the JAK-1 and JAK-3, and, at high concentrations, tyrosine kinase 2 (TYK2) and JAK-2 pathways
    • the JAKs are the downstream signaling molecules of a large number of the cytokine pathways involved in IBD
      • when a cytokine binds its cell surface receptors, it dimerizes the ligand receptors and this results in phosphorylation of the JAK molecules
      • JAK then activates signal transducer and activator of transcription molecules (STATs), the phosphorylation of which results in STAT migration to the nucleus and activation of gene transcription
      • by targeting JAK signaling, it is possible to affect multiple cytokine pathways thought to be involved in colitis.
    • is rapidly absorbed after oral intake with a time to peak concentration of 1/2 h, thus allowing a more comfortable route of administration for the patient and a quicker effect than the majority of other drugs used in inflammatory bowel disease
    • the short half-life of about 3 h requires twice-a-day intake
    • because it is not a monoclonal antibody, it is not antigenic (2)

Reference:

• NICE (28 Nov 2018).Tofacitinib for moderately to severely active ulcerative colitis
• D'Amico F, Parigi TL, Fiorino G, Peyrin-Biroulet L, Danese S. Tofacitinib in the treatment of ulcerative colitis: efficacy and safety from clinical trials to real-world experience. Therap Adv Gastroenterol. 2019;12:1756284819848631. Published 2019 May 16. doi:10.1177/1756284819848631
• Varyani F, Argyriou K, Phillips F, Tsakiridou E, Moran GW. Profile of Tofacitinib in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Recent Data. Drug Des Devel Ther. 2019;13:4091-4105. Published 2019 Dec 2. doi:10.2147/DDDT.S182891