TIME TO LOSS OF EFFICACY AMONG PATIENTS IN REMISSION FOLLOWING INDUCTION TREATMENT WITH TOFACITINIB 10 MG BID WHO REDUCED TOFACITINIB DOSE OR DISCONTINUED TOFACITINIB IN OCTAVE SUSTAIN

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. Safety and efficacy of tofacitinib were evaluated in two Phase 3 induction studies (OCTAVE Induction 1&2; NCT01465763, NCT01458951), a 52-week, Phase 3 maintenance study (OCTAVE Sustain, NCT01458574), and an ongoing, open-label, long-term extension study (NCT01470612).1,2 Here, we assess time to treatment failure among patients in remission at the end of OCTAVE Induction 1&2 who enrolled in OCTAVE Sustain. Methods: In OCTAVE Induction 1&2, patients received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks; clinical responders were re-randomized to placebo, tofacitinib 5 or 10 mg BID in OCTAVE Sustain for 52 weeks. Kaplan-Meier method was used to estimate median time to treatment failure (withdrawal due to insufficient clinical response) in patients who received 10 mg BID in induction studies and entered OCTAVE Sustain in remission (a total Mayo score of ≤2 with no individual subscore?>1, and a rectal bleeding subscore of 0). Treatment failure: a ≥3-point increase from baseline total Mayo score, plus a ≥1-point increase in rectal bleeding subscore and endoscopic subscore (centrally read), and an absolute endoscopic subscore of ≥2 after ≥8 weeks of maintenance therapy. Results: Following induction, 156 patients in remission entered OCTAVE Sustain and received tofacitinib 5 mg BID (N=57) or 10 mg BID (N=50), or placebo (N=49). Estimated treatment failure rates are reported in the table. At Week 52, Kaplan-Meier rates of treatment failure were higher in patients who switched to placebo (81.8% [95% confidence interval 67.0, 90.4]) vs those who continued to receive tofacitinib 10 mg BID (25.6% [14.2, 38.6]) or reduced their dose to 5 mg BID (34.4% [21.8, 47.3]). Median time to treatment failure was 169 days for placebo and?>52 weeks for tofacitinib 5 and 10 mg BID (due to the low number of treatment failure events, exact median time to treatment failure was not available for tofacitinib 5 or 10 mg BID). Conclusion: For patients in remission following 8 weeks of induction treatment with tofacitinib 10 mg BID, median time to treatment failure for those who continued tofacitinib treatment (5 or 10 mg BID) was?>52 weeks. After treatment interruption (remission patients who were re-randomized to placebo), median time to treatment failure was 169 days; this was similar to previously published time-to-treatment-failure data for patients with clinical response (including remission) following 8 weeks of induction treatment with tofacitinib who were re-randomized to placebo.3 References: 1. Sandborn WJ et al. N Engl J Med 2017;376:1723-36 2. Lichtenstein GR et al. Am J Gastroenterol 2019;114:Abstract 704 3. Dubinsky MC et al. Am J Gastroenterol 2018;113:Abstract 725