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DOP024 Tofacitinib achieves symptomatic improvement within 3 days in moderately to severely active ulcerative colitis, regardless of prior tumour necrosis factor inhibitor treatment status: results from OCTAVE induction 1 and 2

S. Hanauer1, R. Panaccione2, S. Danese3, A. Cheifetz4, W. Reinisch5*, P.D.R. Higgins6, D.A. Woodworth7, H. Zhang7, G.S. Friedman7, N. Lawendy7, D. Quirk7, C.I. Nduaka7, C. Su7

1Northwestern University, Evanston, IL, USA, 2University of Calgary, Calgary, AB, Canada, 3Humanitas Research Hospital, IBD Center, Department of Gastroenterology, Rozzano, Milan, Italy, 4Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Medicine and Division of Gastroenterology, Boston, MA, USA, 5Medical University of Vienna, Department of Internal Medicine III, Vienna, Austria, 6University of Michigan, Ann Arbor, MI, USA, 7Pfizer Inc., Collegeville, PA, USA

Background

Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). We evaluated the timing of onset of symptomatic improvement in a post hoc analysis of patient-reported diary data and evaluated treatment effect in patients with and without prior failure of tumour necrosis factor inhibitor (TNFi) therapy.

Methods

OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951) were identical, randomised, placebo-controlled Phase 3 trials in adult patients with moderately to severely active UC who had failed or were intolerant to steroids, immunomodulators or TNFi. Patients received placebo (n = 234) or tofacitinib 10 mg twice daily (N = 905) for 8 weeks. Pooled data for OCTAVE Induction 1 and 2 are presented. During the study, patients recorded their number of bowel movements per day, and the presence and a description of any blood in the stools. Binary endpoints based on Mayo stool frequency (SF) and rectal bleeding (RB) subscores were compared using stratified Cochran–Mantel–Haenszel chi-square test, based on observed data. Subgroup analyses were conducted by prior TNFi failure status, baseline C-reactive protein (CRP) and corticosteroid use at baseline.

Results

At baseline, the mean Mayo subscores for the placebo and tofacitinib groups were 2.5 for SF and 1.6 for RB. By Day 3, significantly more patients achieved each of the binary efficacy endpoints (defined in Table) with tofacitinib vs. placebo (all p < 0.05). Among patients with prior TNFi failure, 117 (26.8%) tofacitinib-treated patients had reduction from baseline SF ≥1 at Day 3, vs. 16 (14.0%) with placebo, and 133 (30.6%) tofacitinib-treated patients had reduction from baseline RB ≥1 at Day 3, vs. 14 (12.5%) with placebo. Subgroup analyses demonstrated generally consistent effects of tofacitinib treatment vs. placebo, regardless of prior TNFi treatment failure status (Figure), baseline CRP and corticosteroid use at baseline.

Conclusion

Significant symptomatic improvements were observed with tofacitinib vs. placebo as early as Day 3. A consistent treatment effect was observed regardless of whether patients had prior TNFi treatment failure. These results support the rapid onset of tofacitinib efficacy previously reported based on significant improvement vs. placebo at 2 weeks in partial Mayo score, and extend this result to response at Day 3.1

Figure. Proportion of patients with (A) reduction from baseline Mayo SF subscore ≥1 point over time, (B) Mayo RB subscore = 0 over time, and (C) reduction from baseline Mayo RB subscore ≥1 point over time, according to prior TNFi failure (yes/no).