In a report published in Clinical Pharmacology & Therapeutics, researchers defined the exposure-response relationship of tofacitinib, a Janus kinase inhibitor, in the induction phase of patients with moderate-to-severe ulcerative colitis. Based on their findings, researchers recommended an induction dose of 10 mg twice a day, with the note that a 5 mg twice a day induction dose was effective in patients who had not previously failed tumor necrosis factor inhibitor (TNFi) therapy.

Additionally, the study reported tofacitinib 5 mg twice a day was effective as a maintenance dose; however, a 10 mg twice-a-day maintenance dose yielded additional clinical benefit, particularly in patients who had failed TNFi therapy.

The study used results from 1355 patients in the OCTAVE 1 and OCTAVE 2 induction studies and 592 patients in the OCTAVE Sustain maintenance study. The researchers’ models estimated week 8 remission rates of 6.4% for tofacitinib 5 mg twice a day and 12.7% for 10 mg twice a day. Respective rates in patients without TNFi failure were 12.8% and 20.4%. In the maintenance phase, estimates for achieving and maintaining remission at week 52 were 29% and 18%, respectively, for 5 mg twice a day and 41% and 26% for 10 mg twice a day.

The authors recommended tofacitinib 10 mg twice a day as an induction dose and 5 mg twice a day as maintenance, with consideration of 10 mg twice a day as maintenance for the shortest possible duration in patients who lose response.

Reference: Mukherjee A, Tsuchiwata S, Nicholas T, et al. Exposure-Response Characterization of Tofacitinib Efficacy in Moderate to Severe Ulcerative Colitis: Results From Phase II and Phase III Induction and Maintenance Studies. Clin Pharmacol Ther. 2022;112(1):90-100. doi:10.1002/cpt.2601