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Digital oral presentations: DOP Session 9 - Treatments for drug failing patients (2020)

DOP81 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

M.C. Dubinsky1, J.W. Chou2, C. Su3, W. Wang3, I. Modesto4, X. Guo3, S. Vermeire5

1Icahn School of Medicine at Mount Sinai, New York, NY, USA, 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan, Province of China, 3Pfizer Inc., Collegeville, PA, USA, 4Pfizer Inc., New York, NY, USA, 5Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium

Background

Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Safety and efficacy of tofacitinib were evaluated in two Phase 3 induction studies (OCTAVE Induction 1 and 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 and 2 who enrolled in OCTAVE Sustain.

Methods

In OCTAVE Induction 1 and 2, patients received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks; clinical responders were re-randomised 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 (total Mayo score ≤2 with no subscore >1, and rectal bleeding subscore [RB] 0). Treatment failure: ≥3-point increase from baseline total Mayo score, plus ≥1-point increase in RB and endoscopic subscore (ES; centrally read) and absolute ES ≥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-randomised 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-randomised to placebo.3.

References:

Sandborn WJ et al. N Engl J Med, 2017;376:1723–36

Lichtenstein GR et al. United European Gastroenterol J, 2019;7:Abstract OP213

Dubinsky MC et al. United European Gastroenterol J, 2018;6:Abstract A121