Efficacy and Safety of Extended Induction With Tofacitinib for the Treatment of Ulcerative Colitis

Clin Gastroenterol Hepatol. 2020 Oct 27;S1542-3565(20)31496-8. doi: 10.1016/j.cgh.2020.10.038. Online ahead of print.

Abstract

Background & aims: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in a dose-ranging phase 2 induction trial, 3 phase 3 randomized, placebo-controlled trials (OCTAVE Induction 1 and 2; and OCTAVE Sustain), and an ongoing, open-label, long-term extension trial (OCTAVE Open) in patients with moderately to severely active UC. Here, we assessed short- and long-term efficacy and safety of extended induction (16 weeks) with tofacitinib 10 mg twice daily (BID) in patients who failed to respond to initial induction (8 weeks) treatment.

Methods: In patients who achieved a clinical response following extended induction (delayed responders), the efficacy and safety of tofacitinib were evaluated up to Month 36 of OCTAVE Open.

Results: 52.2% of patients who did not achieve clinical response to 8 weeks' treatment with tofacitinib 10 mg BID in the induction studies achieved a clinical response following extended induction (delayed responders). At Month 12 of OCTAVE Open, 70.3%, 56.8%, and 44.6% of delayed responders maintained clinical response and achieved endoscopic improvement and remission, respectively. Corresponding values at Month 36 were 56.1%, 52.0%, and 44.6%. The safety profile of the subsequent 8 weeks was similar to the initial 8 weeks.

Conclusions: Overall, the majority of patients achieved a clinical response after 8 or 16 weeks' induction therapy with tofacitinib 10 mg BID. Tofacitinib 10 mg BID, administered as induction therapy for up to 16 weeks, had a comparable safety profile to 8 weeks' induction therapy. Most delayed responders at Month 36 were in remission. ClinicalTrials.gov: NCT00787202; NCT01465763; NCT01458951; and NCT01470612.

Keywords: Induction Therapy; Inflammatory Bowel Disease; Janus Kinase Inhibitor; OCTAVE.

Associated data

  • ClinicalTrials.gov/NCT01465763
  • ClinicalTrials.gov/NCT01470612
  • ClinicalTrials.gov/NCT01458951
  • ClinicalTrials.gov/NCT00787202