Tofacitinib is a small-molecule JAK inhibitor administered orally. Its pharmacologic effect results from inhibition of JAK-mediated cytokine signaling.
Pharmacologic targets
Tofacitinib has functional selectivity for JAK1 and JAK3 over JAK2 at therapeutic concentrations. JAK signaling is involved in the activity of multiple cytokines and immune pathways.
Pharmacokinetics
Current prescribing information describes rapid oral absorption, extensive plasma protein binding and metabolism involving CYP3A4, with CYP2C19 contributing to a lesser degree. The drug is eliminated through both metabolism and renal excretion.
The terminal half-life of immediate-release tofacitinib is approximately 3 hours, while the extended-release formulation provides a different exposure profile suitable for once-daily administration.
Clinical evidence
Tofacitinib’s clinical development included large randomized trials in rheumatoid arthritis. In the ORAL Solo phase 3 trial, 611 patients with active rheumatoid arthritis were randomized to tofacitinib or placebo-based regimens.
The ORAL Start study evaluated tofacitinib against methotrexate in patients with rheumatoid arthritis who had not previously received methotrexate at therapeutic doses.
Ulcerative colitis evidence
The OCTAVE program evaluated induction and maintenance therapy in adults with moderately to severely active ulcerative colitis. In the induction studies, remission at eight weeks was higher with tofacitinib than placebo, while the maintenance study showed higher remission rates with both 5 mg and 10 mg twice-daily regimens than placebo.
Evidence limitations
Clinical-trial results describe groups of participants and cannot predict the response or safety outcome of a particular patient.