P516 Efficacy and safety of tofacitinib retreatment for ulcerative colitis after treatment interruption: Results from the OCTAVE clinical trials

Abstract

Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). It is not expected to elicit neutralising anti-drug antibodies that may limit successful retreatment after treatment interruption. We evaluated tofacitinib retreatment efficacy and safety after treatment interruption in patients with UC in an ongoing, open-label, long-term extension (LTE) study (OCTAVE Open, NCT01470612; data as of July 2016 [efficacy], December 2016 [safety]). OCTAVE1 included induction (OCTAVE Induction 1 and 2), maintenance (OCTAVE Sustain) and LTE (OCTAVE Open) studies. OCTAVE Open included non-responders from OCTAVE Induction 1 and 2 and patients who completed or experienced treatment failure in OCTAVE Sustain. This analysis included the subpopulation of patients in OCTAVE Open who achieved clinical response following 8 weeks of induction therapy with tofacitinib 10 mg twice daily (BID), entered OCTAVE Sustain receiving placebo and experienced treatment failure between Week 8 and up to Week 52, and subsequently entered OCTAVE Open and received tofacitinib 10 mg BID. Treatment failure was defined as increase ≥3 points from maintenance study baseline total Mayo score plus increase in rectal bleeding subscore and endoscopic subscore (ES) ≥1 point and absolute ES ≥2 points after ≥8 weeks of maintenance therapy. We evaluated clinical response, mucosal healing and remission at Months 2 and 12 of OCTAVE Open using non-responder imputation, and evaluated safety throughout the study. Of 914 patients enrolled in OCTAVE Open and treated for ≥2 months at data cut-off, 101 entered OCTAVE Open with clinical response to tofacitinib 10 mg BID in OCTAVE Induction 1 or 2 and treatment failure with placebo during OCTAVE Sustain. After entering OCTAVE Open on tofacitinib 10 mg BID, clinical response, mucosal healing and remission rates were, respectively, 75.8%, 55.4%, and 40.4% at Month 2, and 67.5%, 53.6%, and 43.4% at Month 12 (Table). Safety in the retreatment subpopulation was generally consistent with the overall study population.2 In patients with prior response to tofacitinib, retreatment with 10 mg BID following a period of treatment interruption was efficacious and well-tolerated, with clinical response recaptured in approximately three-quarters of patients by Month 2 and generally sustained at Month 12 with no new safety signals. Interpretation of adverse event rates is limited due to the small sample size. 1. Sandborn WJ et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med, 2017;376:1723–36. 2. Lichtenstein GR et al. Tofacitinib, an oral janus kinase inhibitor, in the treatment of ulcerative colitis: open-label, long-term extension study. Am J Gastroenterol, 2017;112: Abstract 714.