P712 Tofacitinib efficacy in patients with moderate to severe ulcerative colitis: Subgroup analyses of OCTAVE Induction 1 and 2 and OCTAVE Sustain by 5-aminosalicylates use
S. Hanauer1, D. T. Rubin2, P. Gionchetti3, C. Su4, D. A. Woodworth4, D. Quirk4, L. Salese4, W. Wang4, A. Marren4, N. Lawendy4, R. Panaccione*5
1Northwestern University, Feinberg School of Medicine, Chicago, IL, USA, 2University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL, USA, 3University of Bologna, Department of Medical and Surgical Sciences (DIMEC), Bologna, Italy, 4Pfizer Inc., Collegeville, PA, USA, 5University of Calgary, Calgary, AB, Canada
Tofacitinib is an oral, small-molecule JAK inhibitor approved in several countries for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in three Phase 3 trials (OCTAVE Induction 1 and 2, NCT01465763 and NCT01458951; OCTAVE Sustain, NCT01458574) in patients with moderate to severe UC . In this post-hoc analysis, we explored tofacitinib efficacy for patients with (c5-ASA) and without (n5-ASA) concomitant 5-aminosalicylates use.
In OCTAVE Induction 1 and 2, patients received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks; clinical responders were re-randomised into OCTAVE Sustain for 52 weeks and received placebo, tofacitinib 5 or 10 mg BID. c5-ASA were permitted at entry, provided doses were stable ≥4 weeks prior to and during the trials. Remission and mucosal healing were summarised at Week 8 (OCTAVE Induction 1 and 2) and Week 52 (OCTAVE Sustain) by c5-ASA status. Generalised linear models were used to compare the adjusted treatment effects between 5-ASA subgroups (Tables 1 and 2).
A smaller proportion of c5-ASA patients had prior tumour necrosis factor inhibitor (TNFi) and immunosuppressant failure compared with n5-ASA patients, at baseline of OCTAVE Induction and Sustain (OCTAVE Induction 1 and 2: TNFi failure 42.7% vs. 74.5%; immunosuppressant failure 69.4% vs. 78.3%; OCTAVE Sustain: TNFi failure 36% vs. 70%; immunosuppressant failure 67.9% vs. 80%). For both c5-ASA and n5-ASA subgroups, a higher proportion of tofacitinib-treated patients achieved efficacy endpoints, compared with placebo-treated patients, at Week 8 of OCTAVE Induction 1 and 2 and Week 52 of OCTAVE Sustain (Tables 1 and 2). Without controlling for baseline variables, higher treatment effects were observed within the c5-ASA subgroup compared with the n5-ASA subgroup; however, when controlled for prior TNFi and immunosuppressant failure (and baseline remission status in OCTAVE Sustain), the differences were not statistically significant in treatment effects between the 5-ASA subgroups in terms of adjusted odds ratios (Tables 1 and 2).
When controlling for prior UC treatment status, efficacy of tofacitinib, based on adjusted odds ratios, was similar regardless of 5-ASA status. This analysis is limited by subgroup size differences.
1. Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis.