P334 Impact of disease duration on tofacitinib efficacy in patients with ulcerative colitis
S. Travis1, I. Dotan2, S. Danese3, M. Chiorean4, J. Yamamoto-Furusho5, D. Ponce de Leon6, C. Su7, J. Paulissen8, E. Maller7, I. Modesto9, J.F. Colombel10
1Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine- University of Oxford, Oxford, UK, 2Division of Gastroenterology, Rabin Medical Center- Petah Tikva- Israel and Sackler Faculty of Medicine- Tel Aviv University, Tel Aviv, Israel, 3Humanitas University- IBD Center, Division of Gastroenterology- Rozzano, Milan, Italy, 4Virginia Mason Medical Center, Seattle, WA, USA, 5IBD Clinic- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico, 6Pfizer Inc., Lima, Peru, Peru, 7Pfizer Inc., Collegeville, PA, USA, 8Syneos Health, Morrisville, NC, USA, 9Pfizer Inc., New York, NY, USA, 10Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA
Background
Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Safety and efficacy of tofacitinib in patients with UC 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) [1], and an ongoing, open-label, long-term extension study (NCT01470612) [2]. We evaluated the impact of disease duration on tofacitinib efficacy in the OCTAVE trials.
Methods
Patients received tofacitinib 10 mg twice daily (BID) or placebo in OCTAVE Induction 1 and 2, and responders at Week 8 were eligible to receive tofacitinib 5 or 10 mg BID or placebo during OCTAVE Sustain (final efficacy assessment at Week 52). Non-responders from OCTAVE Induction 1 and 2 and completers/treatment failures from OCTAVE Sustain could enter the OLE study. In the OLE study, patients who did not show clinical response to 8 weeks of tofacitinib 10 mg BID in OCTAVE Induction 1 and 2 (induction non-responders [IndNR]) received an additional 8 weeks of tofacitinib 10 mg BID; all patients underwent endoscopy at Month 2 (data as of Sep 2018). Patients were stratified by UC disease duration (<3, 3–6 and >6 years) at OCTAVE Induction 1 and 2 baseline (ie prior to study treatment). Associations between disease duration category and efficacy endpoints were assessed using the Cochran-Mantel–Haenszel Chi-square test.
Results
Among patients who received tofacitinib 10 mg BID in OCTAVE Induction 1 and 2, remission and mucosal healing rates at Week 8 were numerically higher in those with shorter disease duration than those with longer disease duration, but associations were not statistically significant (Table). Clinical response rates were similar across disease duration categories. At Week 52 of OCTAVE sustain, remission and mucosal healing rates were highest in patients with the shortest disease duration (<3 years; Table). Among IndNR, the proportions of patients achieving efficacy endpoints at Month 2 of the OLE study were lowest in those with disease duration <3 years, but associations were not statistically significant (Table).
Conclusion
In general, disease duration did not impact tofacitinib efficacy. Patients diagnosed with UC <3 years prior to starting tofacitinib treatment were numerically more likely to achieve remission and mucosal healing in induction and maintenance trials than those with longer disease duration, but the associations were not statistically significant. These analyses are post hoc and limited by the small sample size, and further data are needed to understand whether disease duration may have an impact on the response to tofacitinib treatment.
Sandborn WJ
Lichtenstein GR