Filgotinib for treating moderately to severely active ulcerative colitis

Filgotinib for treating moderately to severely active ulcerative colitis

NICE state that:

• Filgotinib is recommended, within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults:
  • when conventional or biological treatment cannot be tolerated, or
  • if the disease has not responded well enough or has stopped responding to these treatments, and
  • if the company provides filgotinib according to the commercial arrangement

Notes:

• the Janus kinase (JAK)-signal transducer of activation (STAT) signalling pathway has been implicated in the pathogenesis of inflammatory and autoimmune diseases, such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and inflammatory bowel disease (IBD)
  • JAKs are cytoplasmic tyrosine kinases that associate with cytokine receptors and transduce cytokine signalling via phosphorylation of STATs
    • four different types of JAKs (JAK1, JAK2, JAK3 and TYK2)
    • seven mammalian STAT family members have been identified (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6)
  • JAK1
    • is important in mediating inflammatory cytokine signals
  • JAK2
    • is important in mediating myelopoiesis and erythropoiesis
  • JAK3
    • plays critical roles in immune homeostasis and lymphopoiesis
  • filgotinib is an oral, ATP-competitive, reversible JAK1 preferential inhibitor:
    • modulates the JAK-STAT signalling pathway by preventing the phosphorylation and activation of STATs

Reference:

• NICE (June 2022). Filgotinib for treating moderately to severely active ulcerative colitis
• Dhillon S, Keam SJ. Filgotinib: First Approval [published correction appears in Drugs. 2021 Feb;81(2):297]. Drugs. 2020;80(18):1987-1997. doi:10.1007/s40265-020-01439-0