P383 Relationship between histo-endoscopic mucosal healing and baseline characteristics in patients with moderately to severely active Ulcerative Colitis receiving filgotinib in the phase 2b/3 SELECTION study
Peyrin-Biroulet , L.(1);Loftus Jr , E.V.(2);Hibi , T.(3);Birchwood , C.(4);Yun , C.(4);Zhao , S.(4);Liu , X.(4);Rogler , G.(5);Danese , S.(6);Colombel , J.F.(7);Feagan , B.(8);
(1)University Hospital of Nancy-University of Lorraine, Department of Gastroenterology and Inserm U954, Vandoeuvre-Lès-Nancy, France;(2)Mayo Clinic, Department of Internal Medicine-Department of Gastroenterology and Hepatology, Rochester, United States;(3)Kitasato Institute Hospital-Kitasato University, Center for Advanced IBD Research and Treatment, Tokyo, Japan;(4)Gilead Sciences, Inc., Foster City, United States;(5)University Hospital of Zurich-University of Zurich, Clinic for Gastroenterology and Hepatology, Zurich, Switzerland;(6)Humanitas Clinical and Research Center-IRCCS and Humanitas University, Department of Gastroenterology, Milan, Italy;(7)Icahn School of Medicine at Mount Sinai, The Dr. Henry D. Janowitz Division of Gastroenterology-Department of Medicine, New York City, United States;(8)Western University, Department of Medicine-Division of Gastroenterology, London, Canada
Background
Filgotinib (FIL), an oral preferential Janus kinase 1 inhibitor, was evaluated for the treatment of ulcerative colitis in the phase 2b/3 double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522). Clinical, histological and endoscopic remission rates at week 58 were significantly greater with FIL 200 mg than with PBO (p < 0.025 for all comparisons). Here, we identify disease characteristics contributing to histo-endoscopic mucosal healing (HEMH; Geboes histological remission and endoscopic subscore ≤ 1) at week 58. FIL 100 mg data are excluded from by-treatment summaries because histological and endoscopic remission rates were not significantly different from PBO in SELECTION.
Methods
Eligible patients (18–75 years old) with moderately to severely active ulcerative colitis were enrolled in Induction Study A (biologic-naïve) or B (biologic-experienced) and randomized to receive FIL 200 mg, FIL 100 mg or PBO (2:2:1) once daily for up to 11 weeks, with response assessed at week 10. At week 11, FIL responders were re-randomized 2:1 to continue their induction FIL dose or to receive PBO for the 47-week maintenance study. PBO responders continued receiving PBO. For the maintenance study, univariate logistic regression was used to identify baseline and week 10 disease characteristics associated with HEMH (defined as achieving both Geboes histological remission [Grade 0 of ≤0.3, Grade 1 of ≤ 1.1, Grade 2a of ≤ 2A.3, Grade 2b of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0] and an endoscopic subscore of 0 or 1) at week 58 for patients receiving FIL 200 mg; variables with p < 0.05 in the univariate analysis were included in a multivariate analysis.
Results
Patients had similar characteristics across the treatment groups for both the induction (Table 1) and maintenance studies (Table 2). HEMH was achieved in a greater proportion of patients receiving FIL 200 mg than those receiving respective PBO at week 58 (32.7% vs 10.2%; p < 0.0001). No associations between disease characteristics (at baseline and week 11) and HEMH at week 58 were found (Table 3).
Conclusion
FIL 200 mg was effective at establishing HEMH compared with PBO at week 58; there were no baseline characteristics identified to be associated with HEMH at week 58.