Critical Appraisal of Filgotinib in the Treatment of Ulcerative Colitis: Current Evidence and Place in Therapy

Figures & data

Figure 1 JAK-STAT pathway in the signaling of inflammatory cytokines. JAK proteins are intracellular cytoplasmic tyrosine kinases constitutively associated with intracellular domains of type I and/or type II cytokine receptors; every JAK isoform exhibits binding preferences for different cytokines receptors. Once the extracellular ligand binds the receptor, JAKs activate in pairs via phosphorylation and downstream activate STAT transcription factors. This pathway regulates cellular growth, differentiation, migration, and survival, especially of the T lymphocytes. Created by Biorender.com.

Table 1 Pharmacokinetic and Pharmacodynamic Features of Filgotinib

Feature	Details	Note
Selectivity	Selective blockade of JAK1; JAK1 > JAK2 > JAK3	Filgotinib inhibits JAK1 with a greater potency as compared with JAK3 and TYK2^Citation19
Administration	Oral, as single dose of 100* or 200* mg	Can be administered with or without food without affecting concentrations
Median peak plasma concentration	2 to 3 hours	Rapid absorption
Half-life	Parental molecule = 6 to 7 hours Active metabolite= 21 to 27 hours	Allows both single and repeated dose
Metabolism	Carboxylesterase 2 and carboxylesterase 1	CYP450-independent, relevant for drug-drug interactions
Excretion	Urinary = 85% Fecal = 15%
Dose adjustment	No dose adjustment for CrCl > 60 mL/min	Filgotinib 100 mg per day if CrCl < 60 mL/min
Immunogenicity	None	Further advantage over biologics

Note: *The two currently approved dosages.

Abbreviations: JAK, Janus kinases; CYP450, cytochromes P450; CrCl, creatinine clearance.

Danese S, Argollo M, Le Berre C, Peyrin-Biroulet L. JAK selectivity for inflammatory bowel disease treatment: does it clinically matter? Gut. 2019;68(10):1893–1899. doi:10.1136/gutjnl-2019-318448

 PubMed Web of Science ®Google Scholar