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OP020 Filgotinib, a selective JAK1 inhibitor, induces clinical remission in patients with moderate-to-severe Crohns disease: interim analysis from the Phase 2 FITZROY study

Filgotinib is an oral, selective Janus kinase 1 (JAK1) inhibitor, which has demonstrated high efficacy in patients with rheumatoid arthritis. This 20-week Phase 2 study was designed to evaluate the efficacy and safety of filgotinib in patients with active Crohn’s disease.

In the study, 175 patients with moderate-to-severe Crohn’s disease (CDAI: 220 to 450, endoscopic evidence of active disease) were randomised to receive 200 mg filgotinib (F) or placebo (P) QD (3:1) for 10 weeks. After 10 weeks, patients continued to receive filgotinib (200 mg or 100 mg QD) or P for another 10 weeks. Anti-tumour necrosis factor (TNF)-naïve, as well as anti-TNF nonresponders, were included. Immunosuppressants had to be discontinued. Data from the 10-week induction part are presented, including the primary endpoint of clinical remission (CDAI < 150) at week 10.

Baseline characteristics were comparable in both groups, including mean disease duration (8.3 y), mean CDAI score (293), mean CRP (15.6 mg/L, 41% > 10 mg/L), and oral corticosteroids (49%, mean daily dose 23.2 mg/day). Filgotinib induced clinical remission in 48% of the patients, compared with with 23% in the P arm (p = 0.0067). Significantly more patients in the F arm showed a clinical response (F, 60%; P, 41%; p = 0.0386) and improved quality of life (Inflammatory Bowel Disease Questionnaire [IBDQ] changes from baseline: F, 33.8; P, 17.6; p = 0.0045) than in the P arm. More patients in the F group had their CRP normalised (F, 30%; P, 14%).

Placebo n = 44Filgotinib n = 128p-value
Clinical remission 
(CDAI<150), (%) ITT-NRI23480.0067
Clinical response (CDAI -100 points), (%) ITT-NRI41600.0386
Total Inflammatory Bowel Disease Questionnaire (IBDQ) score, mean change from baseline, ITT-LOCF17.5633.820.0045

In general, F was safe and well tolerated in this patient population. Similar incidences in early discontinuations, SAEs, and AEs including infections were observed, with the majority of the serious adverse events (SAEs) related to worsening of Crohn’s disease. An increase in mean haemoglobin concentration was observed, without difference between F and P. No clinically significant changes from baseline in mean neutrophil counts or liver function tests were observed. Filgotinib showed a favourable lipid profile with an increase in HDL and no change in LDL, resulting in an improved atherogenic index.

Filgotinib is the first Janus kinase (JAK) inhibitor showing efficacy in moderate-to-severe Crohn’s disease patients. Inhibiting JAK1 with F induces clinical remission and response, and improves quality of life. The efficacy and safety data of F suggest a favourable risk/benefit profile, showing its potential as an oral treatment with a novel mechanism of action for the treatment of IBD.

S. Vermeire*1, S. Schreiber2, R. Petryka3, T. Kuehbacher4, X. Hebuterne5, X. Roblin6, M. Klopocka7, E. Goldis8, M. Wisniewska-Jarosinska9, A. Baranovsky10, R. Sike11, C. Tasset12, A. Van der Aa12, P. Harrison12

1UZ Leuven, Campus Gasthuisberg, Leuven, Belgium, 2University Medical Centre Schleswig-Holstein Kiel, Department of Internal Medicine I, Kiel, Germany, 3Vivamed, Warsaw, Poland, 4Asklepios Hospital West Hamburg, Department of Internal Medicine, Gastroenterology, Hamburg, Germany, 5Archet 2 Hospital, Department of Gastroenterology, Nice, France, 6Saint Etienne Hospital, Department of Gastroenterology, Saint Priest en Jarez, France, 7University Hospital Nr. 2 im. Biziela, Department of Gastroenterology, Bydgoszcz, Poland, 8Policlinica Algomed, Department of Gastroenterology, Timisoara, Romania, 9Saint Family Hospital Medical Centre, Department of Gastroenterology and Endoscopy, Lodz, Poland, 10City Clinical Hospital #31, St Petersburg, Russian Federation, 11Szent Margit Hospital, Department of Internal Medicine and Gastroenterology III, Budapest, Hungary, 12Galapagos NV, Department of Development, Mechelen, Belgium