Authors
S. VERMEIRE (1), B. FEAGAN (2), E. LOFTUS JR (3), S. DANESE (4), W. SANDBORN (5), T. RITTER (6), R. MEHTA (7), U. SEIDLER (8), F. SEIBOLD (9), I. BEALES (10), H. JONG KIM (11), J. MCNALLY (12), C. YUN (13), S. ZHAO (14), X. LIU (14), C. TASSET (15), R. BESUYEN (16), M. WATANABE (17), S. SCHREIBER (18), G. ROGLER (19), T. HIBI (20), L. PEYRIN-BIROULET (21) / [1] University Hospitals Leuven, , Belgium, Gastroenterology, [2] Western University, London, Canada, Gastroenterology. , [3] Mayo Clinic, Rochester, United States (the), Gastroenterology and Hepatology, [4] Humanitas University, Milan, Italy, Gastroenterology, [5] University of California San Diego (UCSD), San Diego, United States (the), Gastroenterology, [6] GI Alliance, Southlake, United States (the), Gastroenterology, [7] Surat Institute of Digestive Science, Gujarat , India, Gastroenterology, [8] Hannover Medical School, , Germany, Gastroenterology, [9] Gastroenterological Practice Balsiger, Seibold & Partner Crohn’s Colitis Center, Bern, Switzerland, Gastroenterology, [10] Norfolk and Norwich University Hospital, Norwich, United Kingdom (the), Gastroenterology & General Medicine, [11] Center for Crohn's and Colitis, Kyung Hee University Hospital, Seoul , Korea (the Republic of), Gastroenterology, [12] Gilead Sciences Inc, , United States (the), IBD, [13] Gilead Sciences Inc, , United States (the), Gastroenterology, [14] Gilead Sciences Inc, , United States (the), Biostatistics , [15] Galapagos NV, Mechelen, Belgium, Biotechnology , [16] Galapagos BV, Leiden , Netherlands (the), Gastroenterology, [17] Tokyo Medical and Dental University, Tokyo , Japan, Gastroenterology, [18] University Medical Center Schleswig-Holstein, Kiel, Germany, Gastroenterology, [19] University Hospital, Zurich, Switzerland, Gastroenterology, [20] Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo , Japan, Gastroenterology, [21] Nancy University Hospital, Vandoeuvre-lès-Nancy, France, Gastroenterology
Introduction
Filgotinib (FIL) is a Janus kinase 1 preferential inhibitor being investigated for several inflammatory conditions, including ulcerative colitis (UC).
Aim
The SELECTION (NCT02914522) Induction Studies aimed to evaluate the efficacy and safety of FIL as induction therapy for patients with moderately to severely active UC who were biologic naïve but failed conventional therapy (Cohort A Induction Study) or who had failed prior biologics (Cohort B Induction Study).
Methods
In both induction studies, patients were randomized 2:2:1 to once daily oral FIL 200 mg, FIL 100 mg or placebo (PBO). The primary endpoint for both studies was endoscopic/rectal bleeding/stool frequency (EBS) remission at Week 10, defined by Mayo endoscopic subscore (ES) ≤1, rectal bleeding subscore = 0, and ≥1-pt decrease in stool frequency subscore from baseline and stool frequency subscore ≤1. Key secondary endpoints included Mayo Clinic Score (MCS) remission, endoscopic remission (ES=0), and Geboes histologic remission at Week 10.
Results
In both cohorts, baseline demographics, UC disease characteristics and concomitant UC medications were generally similar across treatment groups. In Cohort A, 659 patients were randomized and treated. At baseline, mean MCS was 8.6 and 56% of patients had severe endoscopic disease (ES=3). 625 (95%) patients completed treatment; the most common reason for treatment discontinuation was an adverse event (AE). A significantly higher proportion of patients treated with FIL 200 mg in Cohort A achieved EBS remission vs. PBO (26.1% vs. 15.3%, respectively [p=0.0157]). In addition, a significantly higher proportion of patients treated with FIL 200 mg vs. PBO achieved all key secondary endpoints. In Cohort B, 689 patients were randomized and treated. At baseline, mean MCS was 9.3 and 78% of patients had ES = 3. Approximately 86% were prior anti-TNF failures, 52% were prior vedolizumab failures and 43% had failed both. 635 (92%) patients completed treatment; the most common reason for treatment discontinuation was an AE. A significantly higher proportion of patients receiving FIL 200 mg in Cohort B achieved EBS remission vs. PBO; 11.5% vs. 4.2% in Cohort B (p=0.0103). Overall, the incidence of AEs, serious AEs and discontinuations due to AEs were similar across FIL and PBO treatment groups. In Cohort A, serious infections occurred in 0.7%, 0.7% and 0.4% of patients in PBO, FIL 100 mg and FIL 200 mg treated groups, respectively, and in 1.4%, 1.4% and 0.8% of patients respectively in Cohort B; herpes zoster infection occurred in 0%, 0% and 0.8% of patients on PBO, FIL 100 mg and FIL 200 mg respectively in Cohort A and in 0%, 0.4% and 0.4% of patients respectively in Cohort B. One patient on FIL 200 mg experienced an opportunistic infection of mild esophageal candidiasis on Day 15 that resolved with treatment. One patient on FIL 200 mg experienced a serious AE of pulmonary embolism on Day 19; the patient’s medical history was significant for hypothyroidism and pulmonary symptoms of unknown origin.
Conclusions
The SELECTION study population included a high proportion of dual-refractory patients, and patients with severe endoscopic disease. Both doses of FIL were well tolerated. Filgotinib 200 mg was effective as an induction treatment for both biologic-naïve and biologic-experienced patients with moderately to severe UC.
