Title: Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

Sandborn, W.J. et al.


What You Need to Know:

Tofacitinib, an oral Janus kinase inhibitor, was found to be more effective than placebo as induction and maintenance therapy in the treatment of moderate-to-severe active ulcerative colitis.

Trial Design:

  • Three, double-blind, randomized, placebo-controlled, phase 3 studies (OCTAVE Induction 1 and 2 trials, OCTAVE Sustain trial) assessed the efficacy of tofacitinib as both induction as well as maintenance therapy in patients with ulcerative colitis
  • Induction trials: patients with active, moderate-to-severe ulcerative colitis, despite previous treatment with conventional therapy or a tumor necrosis factor antagonist, were randomized to receive 10mg tofacitinib twice daily or placebo over 8 weeks
  • Maintenance trial: patients with a clinical response to induction therapy were randomized to receive 5mg or 10mg of tofacitinib twice daily or placebo over 52 weeks
  • Primary endpoints: remission at 8 weeks (OCTAVE Induction trials); remission at 52 weeks (OCTAVE Sustain trial)

Key Outcomes:

  • OCTAVE Induction 1 trial (n=598): 18.5% of tofacitinib patients achieved remission at 8 weeks vs 8.2% of placebo patients (P=0.007)
  • OCTAVE Induction 2 trial (n=541): 16.6% of tofacitinib patients achieved remission at 8 weeks vs 3.6% of placebo patients (P<0.001)
  • OCTAVE Sustain trial (n=593): 34.3% of the 5-mg tofacitinib group and 40.6% of the 10-mg tofacitinib group achieved remission at 52 weeks vs 11.1% of the placebo group (P<0.001 for both comparisons)
  • Induction trials: higher rates of overall infection and serious infection seen in tofacitinib patients vs placebo patients
  • Maintenance trial: similar rate of serious infection seen in all treatment groups, however tofacitinib patients had higher rates of overall infection and herpes zoster infection vs placebo patients
  • All trials: adjudicated nonmelanoma skin cancer occurred in 5 patients treated with tofacitinib and 1 placebo patient; adjudicated cardiovascular events occurred in 5 tofacitinib-treated patients and zero placebo patients; tofacitinib was associated with elevated lipid levels